Author: "Riemekasten, G" / Topic: immunology - Searchworks@Jio Institute Digital Library Search Results

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40 results on '"Riemekasten, G"'

1. Regulatorische T-Zellen und rheumatische Erkrankungen

Author: Humrich, J.Y., Kamradt, T., and Riemekasten, G.
Published: 2015
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2. Geschlechtsspezifische Unterschiede des Immunsystems

Author: Riemekasten, G. and Siegert, E.
Published: 2014
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3. Outcomes of limited cutaneous systemic sclerosis patients: Results on more than 12,000 patients from the EUSTAR database

Author: Frantz C., Huscher D., Avouac J., Hachulla E., Balbir-Gurman A., Riemekasten G., Siegert E., Lazzaroni M. -G., Carreira P. E., Vettori S., Zanatta E., Ullman S., Czirjak L., Kowal-Bielecka O., Distler O., Matucci-Cerinic M., Allanore Y, Cuomo Giovanna, University of Zurich, Allanore, Yannick, Frantz, C., Huscher, D., Avouac, J., Hachulla, E., Balbir-Gurman, A., Riemekasten, G., Siegert, E., Lazzaroni, M. -G., Carreira, P. E., Vettori, S., Zanatta, E., Ullman, S., Czirjak, L., Kowal-Bielecka, O., Distler, O., Matucci-Cerinic, M., Allanore, Y, and Cuomo, Giovanna
Subjects: 0301 basic medicine, Skin score, Limited cutaneous systemic sclerosis, Male, Databases, Factual, Fibrosi, Limited cutaneous systemic sclerosi, Immunology, Digital ulcer, 610 Medicine & health, Interstitial lung disease, Disease, Outcomes, computer.software_genre, Scleroderma, 03 medical and health sciences, FEV1/FVC ratio, Databases, 0302 clinical medicine, Scleroderma, Limited, medicine, Immunology and Allergy, Humans, In patient, Limited, Lung, Factual, Skin, 030203 arthritis & rheumatology, Peripheral Vascular Diseases, 2403 Immunology, integumentary system, Database, business.industry, 10051 Rheumatology Clinic and Institute of Physical Medicine, Digital ulcers, Middle Aged, medicine.disease, Fibrosis, Female, Clinical trial, 030104 developmental biology, 2723 Immunology and Allergy, business, computer
Abstract: Objectives: Limited cutaneous systemic sclerosis (LcSSc) is the most common subset of SSc but it has been overlooked in the past years. At a time at which clinical trials focus on diffuse cutaneous SSc (DcSSc) we aimed at clarifying the outcomes of LcSSc and at evaluating whether potential drug positioned in DcSSc may also be used in LcSSc. Methods: The EUSTAR database was used to investigate skin, lung and peripheral vasculopathy outcomes in LcSSc. Worsening of skin fibrosis, ILD and peripheral vasculopathy were defined by an increase in modified Rodnan skin score (mRSS) > 3.5 points, a decrease of FVC > 10% in patients with ILD at baseline, and by the development of new digital ulcers (DU) in patients without DU at baseline. Results: 8013 LcSSc and 4786 DcSSc patients were included. In contrast to DcSSc, skin disease was remarkably stable in the majority of LcSSc patients with >80% having a change lower than ±4 units of mRSS at 12, 24 and 36 months follow-up. Conversely, FVC changes over time were very similar between LcSSc and DcSSc. Regarding DU, numbers of patients with new DU over time seemed to be almost similar between the two subsets. Conclusions: LcSSc patients have a low mRSS at baseline with marginal changes with time. Conversely, SSc-ILD can be as progressive as in DcSSc supporting the inclusion of LcSSc patients in SSc-ILD trials and suggesting potential benefit of any anti-ILD drugs. Similarly, although slightly less common, DU should receive the same attention in the two subsets.
Published: 2020

4. Racial differences in systemic sclerosis disease presentation: A European Scleroderma Trials and Research group study

Author: Jaeger, Veronika K, Tikly, Mohammed, Dong, Xu, Siegert, Elise, Hachulla, Eric, Airò, Paolo, Valentini, Gabriele, Matucci Cerinic, Marco, Distler, Oliver, Cozzi, Franco, Carreira, Patricia, Allanore, Yannick, Müller-Ladner, Ulf, Ananieva, Lidia P, Balbir-Gurman, Alexandra, Distler, Jörg H W, Czirják, Laszlo, Mengtao, Li, Henes, Jörg, Jimenez, Sergio A, Smith, Vanessa, Damjanov, Nemanja, Denton, Christopher P, Delgaldo, Francesco, Saketkoo, Lesley Ann, Walker, Ulrich, A, Randone, Sb, Bannert, B, Iannone, F, Maurer, B, Jordan, S, Dobrota, R, Becker, M, Mihai, C, Becvarare, R, Tomčík, M, Bielecka, Ok, Gindzienska-Sieskiewicz, E, Karaszewska, K, Cutolo, M, Pizzorni, C, Paolino, S, Sulli, A, Ruaro, B, Alessandri, E, Riccardi, A, Giacco, V, Messitini, V, Irace, R, Kedor, C, Casteleyn, V, Hilger, J, Hoeppner, J, Rednic, S, Szabo, I, Petcu, A, Avouac, J, Camelia, F, Desbas, C, Vlachoyiannopoulos, P, Montecucco, C, Caporali, R, Cavagna, L, Stork, J, Inanc, M, Joven, Be, Novak, S, Anic, F, Varju, C, Minier, T, Chizzolini, C, Allai, D, Kucharz, Ej, Kotulska, A, Kopec-Medrek, M, Widuchowska, M, Dolnicar, As, Coleiro, B, Gabrielli, A, Manfredi, L, Benfaremo, D, Ferrarini, A, Bancel, Df, Hij, A, Lansiaux, P, Lazzaroni, Mg, Hesselstrand, R, Wuttge, D, Andréasson, R, Martinovic, D, Bozic, I, Radic, M, Braun-Moscovici, Y, Monaco, Al, Furini, F, Hunzelmann, N, Moinzadeh, P, Pellerito, R, Caimmi, C, Bertoldo, E, Morovic-Vergles, J, Culo, Im, Pecher, Ac, Santamaria, Vo, Heitmann, S, Codagnone, M, Pflugfelder, J, Krasowska, D, Michalska-Jakubus, M, Seidel, M, Hasler, P, Kretschmar, S, Kohm, M, Bajocchi, G, Salvador, Mj, Silva, Japd, Stamenkovic, B, Stankovic, A, Selmi, Cf, Santis, M, Ceribelli, A, Garzanova, L, Koneva, O, Starovoytova, M, Herrick, A, Puppo, F, Negrini, S, Murdaca, G, Engelhart, M, Szücs, G, Szamosi, S, de la Puente, C, Grande, Cs, Villanueva, Mjg, Midtvedt, Sø, Hoffmann-Vold, Am, Launay, D, Sobanski, V, Riccieri, V, Vasile, M, Ionescu, Rm, Opris, D, Sha, A, Woods, A, Gheorghiu, Am, Bojinca, M, Sunderkötter, C, Ehrchen, J, Ingegnoli, F, Mouthon, L, Dunogue, B, Chaigne, B, Legendre, P, Cantatore, Fp, Corrado, A, Ullman, S, Iversen, L, von Mühlen CA, Pozzi, Mr, Eyerich, K, Lauffer, F, Wiland, P, Szmyrka-Kaczmarek, M, Sokolik, R, Morgiel, E, Madej, M, Vanthuyne, M, Frédéric, H, Alegre-Sancho, Jj, Aringer, M, Herrmann, K, Günther, C, Westhovens, R, Langhe, E, Lenaerts, J, Anic, B, Baresic, M, Mayer, M, Üprus, M, Otsa, K, Yavuz, S, Granel, B, Radominski, Sc, De, C, Müller, S, Azevedo, Vf, Mendoza, F, Busquets, J, Popa, S, Agachi, S, Zenone, T, Pileckyte, M, Stebbings, S, Mathieu, A, Vacca, A, Sampaio-Barros, Pd, Stamp, L, Solanki, K, Silva, C, Schollum, J, Barns-Graham, H, Veale, D, O'Rourke, M, Loyo, E, Tineo, C, Paulino, G, Mohamed, Waaa, Rosato, E, Gigante, A, Oksel, F, Yargucu, F, Tanaseanu, Cm, Popescu, M, Dumitrascu, A, Tiglea, I, Foti, R, Visalli, E, Benenati, A, Amato, G, Ancuta, C, Villiger, P, Adler, S, Fröhlich, J, Kayser, C, Eduardo, Al, Fathi, N, Alii, S, Ahmed, M, Hasaneen, S, Hakeem, Ee, de la PG, Lefebvre, P, Martin, Jjg, Sibilia, J, Chatelus, E, Gottenberg, Je, Chifflot, H, Litinsky, I, Galdo, Fd, Abignano, G, Eng, S, Seskute, G, Butrimiene, I, Rugiene, R, Karpec, D, Pascal, M, Kerzberg, E, Bianchi, W, Bianchi, Bv, Bianchi, Dv, Barcellos, Y, Castellví, I, Millan, M, Limonta, M, Rimar, D, Rosner, I, Slobodin, G, Couto, M, Spertini, F, Ribi, C, Buss, G, Marcoccia, A, Bondanini, F, Ciani, A, Kahl, S, Hsu, Vm, Martin, T, Poindron, V, Meghit, K, Moiseev, S, Novikov, P, Chung, L, Kolstad, K, Stark, M, Schmeiser, T, Thiele, A, Majewski, D, Zdrojewski, Z, Zaneta, S, Wierzba, K, Martínez-Barrio, J, López-Longo, Fj, Bernardino, V, Moraes-Fontes, Mf, Rodrigues, Ac, Riemekasten, G, Sommerlatte, S, Jendreck, S, Arnold, S, Levy, Y, Rezus, E, Cardoneanu, A, Burlui, Am, Pamuk, On, Puttini, Ps, Talotta, R, Bongiovanni, S, Poormoghim, H, Andalib, E, Almasi, S, Kötter, I, Krusche, M, Cuomo, G, Danzo, F, Masini, F, Gaches, F, Michaud, M, Cartos, F, Belloli, L, Casu, C, Sfikakis, P, Tektonidou, M, Furst, D, Feldman, Gr, Ramazan, Am, Nurmambet, E, Miroto, A, Suta, C, Andronache, I, Huizinga, Twj, de Vries-Bouwstra, J., Chizzolini, Carlo, Jaeger, Veronika K, Tikly, Mohammed, Xu, Dong, Siegert, Elise, Hachulla, Eric, Airò, Paolo, Valentini, Gabriele, Matucci Cerinic, Marco, Distler, Oliver, Cozzi, Franco, Carreira, Patricia, Allanore, Yannick, Müller-Ladner, Ulf, Ananieva, Lidia P, Balbir-Gurman, Alexandra, Distler, Jörg H W, Czirják, Laszlo, Li, Mengtao, Henes, Jörg, Jimenez, Sergio A, Smith, Vanessa, Damjanov, Nemanja, Denton, Christopher P, Delgaldo, Francesco, Saketkoo, Lesley Ann, Walker, Ulrich A, University of Zurich, Cerinic, Marco Matucci, Walker Ulrich, A, Randone, Silvia Bellando, Bannert, Bettina, Iannone, Florenzoaa, Maurer, Brittaab, Jordan, Suzanaab, Dobrota, Rucsandraab, Becker, Mikeab, Mihai, Carinaa, Becvarare, Radima, Tomcik, Michala, Bielecka, Otylia Kowala, Gindzienska-Sieskiewicz, Ewaa, Karaszewska, Katarzynaa, Cutolo, Maurizioa, Pizzorni, Carmena, Paolino, Sabrinaae, Sulli, Albertoa, Ruaro, Barbara, Alessandri, Elisa, Riccardi, Antonella, Giacco, Veronica, Messitini, Valentina, Irace, Rosaria, Kedor, Claudia, Casteleyn, Vincent, Hilger, Julia, Hoeppner, Jakob, Rednic, Simona, Szabo, Iulia, Petcu, Ana, Avouac, Jérome, Camelia, Frantz, Desbas, Carole, Vlachoyiannopoulos, Panayioti, Montecucco, Carlo Maurizio, Caporali, Roberto, Cavagna, Lorenzo, Stork, Jiri, Inanc, Murat, Joven, Beatriz E., Novak, Srdan, Anic, Felina, Varju, Cecilia, Minier, Tunde, Allai, Daniela, Kucharz, Eugene J., Kotulska, Anna, Kopec-Medrek, Magdalena, Widuchowska, Malgorzata, Dolnicar, Alenka Sipek, Coleiro, Bernard, Gabrielli, Armando, Manfredi, Lucia, Benfaremo, Devi, Ferrarini, Alessia, Bancel, Dominique Farge, Hij, Adrian, Lazzaroni, Maria Grazia, Hesselstrand, Roger, Wuttge, Dirk, Andréasson, Kristofer, Martinovic, Duska, Bozic, Ivona, Radic, Mislav, Braun-Moscovici, Yolanda, Monaco, Andrea Lo, Furini, Federica, Hunzelmann, Nicola, Moinzadeh, Pia, Pellerito, Raffaele, Caimmi, Cristian, Bertoldo, Eugenia, Morovic-Vergles, Jadranka, Culo, Ivana Melanie, Pecher, Ann-Christian, Santamaria, Vera Ortiz, Heitmann, Stefan, Codagnone, Medeleine, Pflugfelder, Johanne, Krasowska, Dorota, Michalska-Jakubus, Malgorzata, Seidel, Matthia, Hasler, Paul, Kretschmar, Samuel, Kohm, Michaela, Bajocchi, Gianluigi, Salvador, Maria João, Da Silva, JoséAntonio Pereira, Stamenkovic, Bojana, Stankovic, Aleksandra, Selmi, Carlo Francesco, De Santis, Maria, Ceribelli, Angela, Garzanova, Ludmila, Koneva, Olga, Starovoytova, Maya, Herrick, Ariane, Puppo, Francesco, Negrini, Simone, Murdaca, Giuseppe, Engelhart, Merete, Szücs, Gabriela, Szamosi, Szilvia, De La Puente, Carlo, Grande, Cristina Sobrino, Villanueva, Maria Jesus Garcia, Midtve, Øyvindbw, Hoffmann-Vold, Anna-Mariabw, Launay, Davidbx, Sobanski, Vincentbx, Riccieri, Valeriaby, Vasile, Massimilianoby, Stefantoni, Katia, Ionescu, Ruxandra Maria, Opris, Daniela, Sha, Ami, Woods, Adrianne, Gheorghiu, Ana Maria, Bojinca, Mihai, Sunderkötter, Cord, Ehrchen, Jan, Ingegnoli, Francesca, Mouthon, Luc, Dunogue, Bertrand, Chaigne, Benjamin, Legendre, Paul, Cantatore, Francesco Paolo, Corrado, Ada, Ullman, Susanne, Iversen, Line, Von Mühlen, Carlos Alberto, Pozzi, Maria Rosa, Eyerich, Kilian, Lauffer, Felix, Wiland, Piotr, Szmyrka-Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Madej, Marta, Vanthuyne, Marie, Frédéric, Houssiau, Alegre-Sancho, Juan Jose, Aringer, Martin, Herrmann, Kristine, Günther, Claudia, Westhovens, Rene, De Langhe, Ellen, Lenaerts, Jan, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Üprus, Maria, Otsa, Kati, Yavuz, Sule, Granel, Brigitte, Radominski, Sebastião Cezar, De Souza Müller, Carolina, Feijóazevedo, Valderílio, Mendoza, Fabian, Busquets, Joanna, Popa, Sergei, Agachi, Svetlana, Zenone, Thierry, Pileckyte, Margarita, Stebbings, Simon, Jordan, Sarah, Mathieu, Alessandro, Vacca, Alessandra, Sampaio-Barros, Percival D., Stamp, Lisa, Solanki, Kamal, Silva, Cherumi, Schollum, Joanne, Barns-Graham, Helen, Veale, Dougla, O'Rourke, Marie, Loyo, Esthela, Tineo, Carmen, Paulino, Glenny, Mohamed, Walid Ahmed Abdel Atty, Rosato, Edoardo, Gigante, Antonietta, Oksel, Fahrettin, Yargucu, Figen, Tanaseanu, Cristina-Mihaela, Popescu, Monica, Dumitrascu, Alina, Tiglea, Isabela, Foti, Rosario, Visalli, Elisa, Benenati, Alessia, Amato, Giorgio, Ancuta, Codrina, Villiger, Peter, Adler, Sabine, Fröhlich, Johanne, Kayser, Cristiane, Eduardo, Andrade Lui, Fathi, Nihal, Alii, Safa, Ahmed, Marrow, Hasaneen, Samar, El Hakeem, Eman, De La Peña Lefebvre, Paloma García, Martin, Jorge Juan Gonzalez, Sibilia, Jean, Chatelus, Emmanuel, Gottenberg, Jacques Eric, Chifflot, Hélène, Litinsky, Ira, Del Galdo, Francesco, Abignano, Giuseppina, Eng, Sookho, Seskute, Goda, Butrimiene, Irena, Rugiene, Rita, Karpec, Diana, Pascal, Melanie, Kerzberg, Eduardo, Bianchi, Washington, Bianchi, Breno Valdetaro, Bianchi, Dante Valdetaro, Barcellos, Yeda, Castellví, Ivan, Millan, Milena, Limonta, Massimiliano, Rimar, Doron, Rosner, Itzhak, Slobodin, Gleb, Couto, Maura, Spertini, Françoi, Ribi, Camillo, Buss, Guillaume, Marcoccia, Antonella, Bondanini, Francesco, Ciani, Aldo, Kahl, Sarah, Hsu, Vivien M., Martin, Thierry, Poindron, Vincent, Meghit, Kilifa, Moiseev, Sergey, Novikov, Pavel, Chung, Lori, Kolstad, Kathleen, Stark, Marianna, Schmeiser, Tim, Thiele, Astrid, Majewski, Dominik, Zdrojewski, Zbigniew, Zaneta, Smolenska, Wierzba, Karol, Martínez-Barrio, Julia, López-Longo, Francisco Javier, Bernardino, Vera, Moraes-Fontes, Maria Francisca, Rodrigues, Ana Catarina, Riemekasten, Gabriela, Sommerlatte, Sabine, Jendreck, Sebastian, Arnold, Sabrina, Levy, Yair, Rezus, Elena, Cardoneanu, Anca, Burlui, Alexandra Maria, Pamuk, Omer Nuri, Puttini, Piercarlo Sarzi, Talotta, Rossella, Bongiovanni, Sara, Poormoghim, Hadi, Andalib, Elham, Almasi, Simin, Kötter, Ina, Krusche, Matrin, Cuomo, Giovanna, Danzo, Fiammetta, Masini, Francesco, Gaches, Franci, Michaud, Martin, Cartos, Florian, Belloli, Laura, Casu, Cinzia, Sfikakis, Petro, Tektonidou, Maria, Furst, Daniel, Feldman, Gary R., Ramazan, Ana-Maria, Nurmambet, Emel, Miroto, Amalia, Suta, Cristina, Andronache, Iulia, Huizinga, Tom W. J., De Vries-Bouwstra, Jeska, and Walker, Ulrich A.
Subjects: Male, Vital capacity, Organ manifestations, systemic sclerosis, Type I, race difference, Systemic scleroderma, Gastroenterology, Scleroderma, immunology, 0302 clinical medicine, Diffusing capacity, middle aged, pulmonary hypertension, Medicine, Pharmacology (medical), 030212 general & internal medicine, organ manifestations, races, skin and connective tissue diseases, Lung, race, pathophysiology, African Continental Ancestry Group, ddc:616, integumentary system, disease course, Hazard ratio, Races, 10051 Rheumatology Clinic and Institute of Physical Medicine, Pulmonary, Middle Aged, Blacks, cohort analysis, Autoantibodie, 3. Good health, Asians, female, priority journal, DNA Topoisomerases, Type I, Black, centromere, Cohort, Hypertension, organ manifestation, Systemic sclerosis, Female, systemic sclerosi, Human, Adult, Asian Continental Ancestry Group, medicine.medical_specialty, Hypertension, Pulmonary, European Continental Ancestry Group, Black People, 610 Medicine & health, complication, Caucasian, White People, Article, lung, 03 medical and health sciences, Black person, Rheumatology, Asian People, forced vital capacity, Internal medicine, geographic distribution, Humans, controlled study, human, DNA topoisomerase, Aged, Autoantibodies, 030203 arthritis & rheumatology, Scleroderma, Systemic, Asian, business.industry, Whites, Systemic, Odds ratio, medicine.disease, Pulmonary hypertension, major clinical study, mortality, clinical feature, business, DNA Topoisomerases, autoantibody
Abstract: Objectives Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations. Methods SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses. Results The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP. AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001]. Conclusion Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality.
Published: 2020

5. Update of EULAR recommendations for the treatment of systemic sclerosis

Author: Kowal-Bielecka O., Fransen J., Avouac J., Becker M., Kulak A., Allanore Y., Distler O., Clements P., Cutolo M., Czirjak L., Damjanov N., Del Galdo F., Denton C. P., Distler J. H. W., Foeldvari I., Figelstone K., Frerix M., Furst D. E., Guiducci S., Hunzelmann N., Khanna D., Matucci-Cerinic M., Herrick A. L., Van Den Hoogen F., Van Laar J. M., Riemekasten G., Silver R., Smith V., Sulli A., Tarner I., Tyndall A., Welling J., Wigley F., Valentini G., Walker U. A., Zulian F., Muller-Ladner U., Daikeler T., Lanciano E., Becvar R., Tomcik M., Gindzienska-Sieskiewicz E., Cuomo G., Iudici M., Rednic S., Vlachoyiannopoulos P. G., Caporali R., Carreira P. E., Novak S., Minier T., Kucharz E. J., Gabrielli A., Moroncini G., Airo' P., Hesselstrand R., Martinovic D., Radic M., Marasovic-Krstulovic D., Braun-Moscovici Y., Balbir-Gurman A., Lo Monaco A., Caramaschi P., Morovic-Vergles J., Henes J., Ortiz Santamaria V., Heitmann S., Krasowska D., Seidel M. F., Hasler P., Pereira Da Silva J. A., Salvador M. J., Stamenkovic B., Stankovic A., Tikly M., Ananieva L. P., Beretta L., Szucs G., Szamosi S., de la Puente Bujidos C., Midtvedt O., Hoffmann-Vold A. -M., Launay D., Hachulla E., Riccieri V., Ionescu R., Opris D., Mihai C., Herrgott I., Beyer C., Ingegnoli F., von Muhlen C. A., Alegre-Sancho J. J., Beltran-Catalan E., Aringer M., Fantana J., Leuchten N., Tausche A. -K., De Langhe E., Vanthuyne M., Anic B., Baresic M., Mayer M., Uprus M., Otsa K., Yavuz S., Granel B., Azevedo V. F., Muller C., Jimenez S. A., Popa S., Agachi S., Zenone T., Stebbings S., Dockerty J., Vacca A., Schollum J., Veale D. J., Toloza S., Xu D., Olas J., Rosato E., Foti R., Adler S., Dan D., Wiesik-Szewczyk E., Olesinska M., Kayser C., Fathi N., de la Pena Lefebvre P. G., Imbert B., Kowal-Bielecka, O., Fransen, J., Avouac, J., Becker, M., Kulak, A., Allanore, Y., Distler, O., Clements, P., Cutolo, M., Czirjak, L., Damjanov, N., Del Galdo, F., Denton, C. P., Distler, J. H. W., Foeldvari, I., Figelstone, K., Frerix, M., Furst, D. E., Guiducci, S., Hunzelmann, N., Khanna, D., Matucci-Cerinic, M., Herrick, A. L., Van Den Hoogen, F., Van Laar, J. M., Riemekasten, G., Silver, R., Smith, V., Sulli, A., Tarner, I., Tyndall, A., Welling, J., Wigley, F., Valentini, G., Walker, U. A., Zulian, F., Muller-Ladner, U., Daikeler, T., Lanciano, E., Becvar, R., Tomcik, M., Gindzienska-Sieskiewicz, E., Cuomo, G., Iudici, M., Rednic, S., Vlachoyiannopoulos, P. G., Caporali, R., Carreira, P. E., Novak, S., Minier, T., Kucharz, E. J., Gabrielli, A., Moroncini, G., Airo', P., Hesselstrand, R., Martinovic, D., Radic, M., Marasovic-Krstulovic, D., Braun-Moscovici, Y., Balbir-Gurman, A., Lo Monaco, A., Caramaschi, P., Morovic-Vergles, J., Henes, J., Ortiz Santamaria, V., Heitmann, S., Krasowska, D., Seidel, M. F., Hasler, P., Pereira Da Silva, J. A., Salvador, M. J., Stamenkovic, B., Stankovic, A., Tikly, M., Ananieva, L. P., Beretta, L., Szucs, G., Szamosi, S., de la Puente Bujidos, C., Midtvedt, O., Hoffmann-Vold, A. -M., Launay, D., Hachulla, E., Riccieri, V., Ionescu, R., Opris, D., Mihai, C., Herrgott, I., Beyer, C., Ingegnoli, F., von Muhlen, C. A., Alegre-Sancho, J. J., Beltran-Catalan, E., Aringer, M., Fantana, J., Leuchten, N., Tausche, A. -K., De Langhe, E., Vanthuyne, M., Anic, B., Baresic, M., Mayer, M., Uprus, M., Otsa, K., Yavuz, S., Granel, B., Azevedo, V. F., Muller, C., Jimenez, S. A., Popa, S., Agachi, S., Zenone, T., Stebbings, S., Dockerty, J., Vacca, A., Schollum, J., Veale, D. J., Toloza, S., Xu, D., Olas, J., Rosato, E., Foti, R., Adler, S., Dan, D., Wiesik-Szewczyk, E., Olesinska, M., Kayser, C., Fathi, N., de la Pena Lefebvre, P. G., Imbert, B., UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (MGD) Service de rhumatologie, Kowal Bielecka, Otylia, Fransen, Jaap, Avouac, Jerome, Becker, Mike, Kulak, Agnieszka, Allanore, Yannick, Distler, Oliver, Clements, Philip, Cutolo, Maurizio, Czirjak, Laszlo, Damjanov, Nemanja, del Galdo, Francesco, Denton, Christopher P., Distler, JÃ¶rg H. W., Foeldvari, Ivan, Figelstone, Kim, Frerix, Marc, Furst, Daniel E., Guiducci, Serena, Hunzelmann, Nicola, Khanna, Dinesh, Matucci Cerinic, Marco, Herrick, Ariane L., van den Hoogen, Frank, van Laar, Jacob M., Riemekasten, Gabriela, Silver, Richard, Smith, Vanessa, Sulli, Alberto, Tarner, Ingo, Tyndall, Alan, Welling, Joep, Wigley, Frederic, Valentini, Gabriele, Walker, Ulrich A., Zulian, Francesco, MÃ¼ller Ladner, Ulf, Daikeler, Thoma, Lanciano, Elisabetta, Becvã¡r, Radim, Tomcik, Michal, Gindzienska Sieskiewicz, Ewa, Iudici, Michele, Rednic, Simona, Vlachoyiannopoulos, Panayiotis G., Caporali, Roberto, Carreira, Patricia E., Novak, Srdan, Minier, Tã¼nde, Kucharz, Eugene J., Gabrielli, Armando, Moroncini, Gianluca, Airo, Paolo, Hesselstrand, Roger, Martinovic, Duska, Radic, Mislav, Marasovic Krstulovic, Daniela, Braun Moscovici, Yolanda, Monaco, Andrea Lo, Morovic Vergles, Jadranka, Culo, Melanie I., Henes, Jã¶rg, Santamaria, Vera Ortiz, Heitmann, Stefan, Krasowska, Dorota, Michalska Jakubus, Malgorzata, Seidel, Matthias F., Klinik III, Medizinische, Hasler, Paul, Da Silva, JosÃ© A. Pereira, Salvador, Maria J., Stamenkovic, Bojana, Stankovic, Aleksandra, Tikly, Mohammed, Ananieva, Lidia P., Beretta, Lorenzo, Szucs, Gabriella, Szamosi, Szilvia, de la Puente Bujidos, Carlo, Midtvedt, Ã˜yvind, Hoffmann Vold, Anna Maria, Launay, David, Hachulla, Eric, Riccieri, Valeria, Ionescu, Ruxandra, Opris, Daniela, Mihai, Carina, Herrgott, Ilka, Beyer, Christian, Ingegnoli, Francesca, von MÃ¼hlen, Carlos Alberto, Alegre Sancho, Juan JosÃ©, Beltran Catalan, Emma, Aringer, Martin, Fantana, Julia, Leuchten, Nicolai, Tausche, Anne Kathrin, Langhe, Ellen De, Vanthuyne, Marie, Anic, Branimir, Bareå¡ic, Marko, Mayer, Miroslav, Ãœprus, Maria, Otsa, Kati, Yavuz, Sule, Granel, Brigitte, Jimenez, Sergio A., Popa, Serghei, Agachi, Svetlana, Zenone, Thierry, Stebbings, Simon, Dockerty, Joanne, Vacca, Alessandra, Schollum, Joanna, Veale, Douglas J., Toloza, Sergio, Xu, Dong, Olas, Jacek, Rosato, Edoardo, Foti, Rosario, Adler, Sabine, Dan, Diana, Wiesik Szewczyk, Ewa, Olesinska, Marzena, Kayser, Cristiane, Fathi, Nihal, de la PeÃ±a Lefebvre, Paloma GarcÃa, Imbert, Bernard, and Cuomo, Giovanna
Subjects: Endothelin Receptor Antagonists, Lung Diseases, Kidney Disease, Delphi Technique, Gastrointestinal Diseases, systemic sclerosis, Scleroderma Renal Crisis, Placebo-controlled study, Angiotensin-Converting Enzyme Inhibitors, Lung Disease, Scleroderma, 0302 clinical medicine, Glucocorticoid, Phosphodiesterase 5 Inhibitor, Immunology and Allergy, skin and connective tissue diseases, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, integumentary system, treatment, genetics and molecular biology (all), Hematopoietic Stem Cell Transplantation, cyclophosphamide, methotrexate, Pulmonary, Orvostudományok, Serotonin Uptake Inhibitor, 3. Good health, Europe, Systematic review, Hypertension, Serotonin Uptake Inhibitors, Cyclophosphamide, Methotrexate, Systemic Sclerosis, Treatment, Fingers, Fluoxetine, Glucocorticoids, Humans, Hypertension, Pulmonary, Kidney Diseases, Phosphodiesterase 5 Inhibitors, Prostaglandins I, Pyrazoles, Pyrimidines, Raynaud Disease, Rheumatology, Scleroderma, Systemic, Ulcer, Immunology, Biochemistry, Genetics and Molecular Biology (all), 030211 gastroenterology & hepatology, Endothelin Receptor Antagonist, Selective Serotonin Reuptake Inhibitors, medicine.drug, Human, medicine.medical_specialty, Gastrointestinal Disease, Klinikai orvostudományok, Riociguat, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, medicine, Finger, biochemistry, Intensive care medicine, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, Systemic Sclerosi, 030203 arthritis & rheumatology, business.industry, Systemic, Angiotensin-Converting Enzyme Inhibitor, medicine.disease, Transplantation, Clinical research, Pyrimidine, immunology and allergy, rheumatology, immunology, Pyrazole, Physical therapy, business, Rheumatism
Abstract: The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
Published: 2017

6. What have multicentre registries across the world taught us about the disease features of systemic sclerosis?

Author: Proudman S. M., Huq M., Stevens W., Wilson M. E., Sahhar J., Baron M., Hudson M., Pope J., Allanore Y., Distler O., Kowal-Bielecka O., Matucci-Cerinic M., H. L. Low A., Teng G. G., Law W. G., Santosa A., Nikpour M., Hill C., Lester S., Nash P., Ngian G. -S., Proudman S., Rischmueller M., Roddy J., Strickland G., Thakkar V., Walker J., Zochling J., Markland J., Robinson D., Jones N., Khalidi N., Docherty P., Kaminska E., Masetto A., Sutton E., Mathieu J. -P., Ligier S., Grodzicky T., LeClercq S., Thorne C., Gyger G., Smith D., Fortin P. R., Larche M., Abu-Hakima M., Rodriguez-Reyna T. S., Cabral A. R., Fritzler M., Avouac J., Walker U. A., Guiducci S., Riemekasten G., Air P., Hachulla E., Valentini G., Carreira P. E., Cozzi F., Gurman A. B., Braun-Moscovici Y., Damjanov N., Ananieva L. P., Scorza R., Jimenez S., Busquets J., Li M., Muller-Ladner U., Maurer B., Tyndall A., Lapadula G., Iannone F., Becvar R., Sierakowsky S., Cutolo M., Sulli A., Cuomo G., Vettori S., Rednic S., Nicoara I., Vlachoyiannopoulos P., Montecucco C., Caporali R., Novak S., Czirjak L., Varju C., Chizzolini C., Kucharz E. J., Kotulska A., Kopec-Medrek M., Widuchowska M., Rozman B., Mallia C., Coleiro B., Gabrielli A., Farge D., Hij A., Hesselstrand R., Scheja A., Wollheim F., Martinovic D., Govoni M., Lo Monaco A., Hunzelmann N., Pellerito R., Bambara L. M., Caramaschi P., Black C., Denton C., Henes J., Santamaria V. O., Heitmann S., Krasowska D., Seidel M., Oleszowsky M., Burkhardt H., Himsel A., Salvador M. J., Stamenkovic B., Stankovic A., Tikly M., Starovoytova M. N., Engelhart M., Strauss G., Nielsen H., Damgaard K., Szucs G., Mendoza A. Z., de la Puente Buijdos C., Giraldo W. A. S., Midtvedt O., Garen T., Launay D., Valesini G., Riccieri V., Ionescu R. M., Opris D., Groseanu L., Wigley F. M., Mihai C. M., Cornateanu R. S., Ionitescu R., Gherghe A. M., Gorga M., Dobrota R., Bojinca M., Schett G., Distler J. H., Meroni P., Zeni S., Mouthon L., De Keyser F., Smith V., Cantatore F. P., Corrado A., Ullman S., Iversen L., Pozzi M. R., Eyerich K., Hein R., Knott E., Szechinski J., Wiland P., Szmyrka-Kaczmarek M., Sokolik R., Morgiel E., Krummel-Lorenz B., Saar P., Aringer M., Gunther C., Anic B., Baresic M., Mayer M., Radominski S. C., de Souza Muller C., Azevedo V. F., Agachi S., Groppa L., Chiaburu L., Russu E., Zenone T., Stebbings S., Highton J., Stamp L., Chapman P., O'Donnell J., Solanki K., Doube A., Veale D., O'Rourke M., Loyo E., Rosato E., Pisarri S., Tanaseanu C. -M., Popescu M., Dumitrascu A., Tiglea I., Chirieac R., Ancuta C., Furst D. E., Kafaja S., Garcia de la Pena Lefebvre P., Rubio S. R., Exposito M. V., Sibilia J., Chatelus E., Gottenberg J. E., Chifflot H., Litinsky I., Venalis A., Butrimiene I., Venalis P., Rugiene R., Karpec D., Kerzberg E., Montoya F., Cosentino V., Low A. H. L., Teng G., Chan G., Lim A. Y. N., Ng S. C., Proudman, S. M., Huq, M., Stevens, W., Wilson, M. E., Sahhar, J., Baron, M., Hudson, M., Pope, J., Allanore, Y., Distler, O., Kowal-Bielecka, O., Matucci-Cerinic, M., H. L. Low, A., Teng, G. G., Law, W. G., Santosa, A., Nikpour, M., Hill, C., Lester, S., Nash, P., Ngian, G. -S., Proudman, S., Rischmueller, M., Roddy, J., Strickland, G., Thakkar, V., Walker, J., Zochling, J., Markland, J., Robinson, D., Jones, N., Khalidi, N., Docherty, P., Kaminska, E., Masetto, A., Sutton, E., Mathieu, J. -P., Ligier, S., Grodzicky, T., Leclercq, S., Thorne, C., Gyger, G., Smith, D., Fortin, P. R., Larche, M., Abu-Hakima, M., Rodriguez-Reyna, T. S., Cabral, A. R., Fritzler, M., Avouac, J., Walker, U. A., Guiducci, S., Riemekasten, G., Air, P., Hachulla, E., Valentini, G., Carreira, P. E., Cozzi, F., Gurman, A. B., Braun-Moscovici, Y., Damjanov, N., Ananieva, L. P., Scorza, R., Jimenez, S., Busquets, J., Li, M., Muller-Ladner, U., Maurer, B., Tyndall, A., Lapadula, G., Iannone, F., Becvar, R., Sierakowsky, S., Cutolo, M., Sulli, A., Cuomo, G., Vettori, S., Rednic, S., Nicoara, I., Vlachoyiannopoulos, P., Montecucco, C., Caporali, R., Novak, S., Czirjak, L., Varju, C., Chizzolini, C., Kucharz, E. J., Kotulska, A., Kopec-Medrek, M., Widuchowska, M., Rozman, B., Mallia, C., Coleiro, B., Gabrielli, A., Farge, D., Hij, A., Hesselstrand, R., Scheja, A., Wollheim, F., Martinovic, D., Govoni, M., Lo Monaco, A., Hunzelmann, N., Pellerito, R., Bambara, L. M., Caramaschi, P., Black, C., Denton, C., Henes, J., Santamaria, V. O., Heitmann, S., Krasowska, D., Seidel, M., Oleszowsky, M., Burkhardt, H., Himsel, A., Salvador, M. J., Stamenkovic, B., Stankovic, A., Tikly, M., Starovoytova, M. N., Engelhart, M., Strauss, G., Nielsen, H., Damgaard, K., Szucs, G., Mendoza, A. Z., de la Puente Buijdos, C., Giraldo, W. A. S., Midtvedt, O., Garen, T., Launay, D., Valesini, G., Riccieri, V., Ionescu, R. M., Opris, D., Groseanu, L., Wigley, F. M., Mihai, C. M., Cornateanu, R. S., Ionitescu, R., Gherghe, A. M., Gorga, M., Dobrota, R., Bojinca, M., Schett, G., Distler, J. H., Meroni, P., Zeni, S., Mouthon, L., De Keyser, F., Smith, V., Cantatore, F. P., Corrado, A., Ullman, S., Iversen, L., Pozzi, M. R., Eyerich, K., Hein, R., Knott, E., Szechinski, J., Wiland, P., Szmyrka-Kaczmarek, M., Sokolik, R., Morgiel, E., Krummel-Lorenz, B., Saar, P., Aringer, M., Gunther, C., Anic, B., Baresic, M., Mayer, M., Radominski, S. C., de Souza Muller, C., Azevedo, V. F., Agachi, S., Groppa, L., Chiaburu, L., Russu, E., Zenone, T., Stebbings, S., Highton, J., Stamp, L., Chapman, P., O'Donnell, J., Solanki, K., Doube, A., Veale, D., O'Rourke, M., Loyo, E., Rosato, E., Pisarri, S., Tanaseanu, C. -M., Popescu, M., Dumitrascu, A., Tiglea, I., Chirieac, R., Ancuta, C., Furst, D. E., Kafaja, S., Garcia de la Pena Lefebvre, P., Rubio, S. R., Exposito, M. V., Sibilia, J., Chatelus, E., Gottenberg, J. E., Chifflot, H., Litinsky, I., Venalis, A., Butrimiene, I., Venalis, P., Rugiene, R., Karpec, D., Kerzberg, E., Montoya, F., Cosentino, V., Low, A. H. L., Teng, G., Chan, G., Lim, A. Y. N., and Ng, S. C.
Subjects: 0301 basic medicine, medicine.medical_specialty, Pediatrics, Survival, Immunology, Disease, Scleroderma, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Immunology and Allergy, Medicine, Multicentre registrie, 030203 arthritis & rheumatology, Clinical features, Cohort study, Multicentre registries, Systemic sclerosis, business.industry, Interstitial lung disease, Autoantibody, Clinical features, medicine.disease, 030104 developmental biology, Clinical feature, Cohort, business, Cohort study, Rheumatism
Abstract: Introduction The aim of this study is to compare the clinical features, mortality and causes of death of systemic sclerosis (SSc) patients in four large multicentre registries. Methods Patients seen at least once in the Australian Scleroderma Cohort Study (ASCS) (n = 1714), the Canadian Scleroderma Research Group (CSRG) (n = 1628), the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) Network (n = 13,996) and the Systemic Sclerosis Cohort in Singapore (SCORE) (n = 500) before August 2016 were included. Clinical manifestations and survival in cohorts and disease subtypes were compared. Results Among 17,838 SSc patients, most were female (86.1%), Caucasian (84.6%) and had the limited cutaneous subtype (lcSSc) (65.0%). The anti-centromere autoantibody was the most prevalent (37.6%). More patients in SCORE had the diffuse subtype (dcSSc) (49.3%) and Scl-70 autoantibody (38.8%) (pConclusions This meta-cohort of SSc patients, the largest reported to date, provides insights into the impact of race and sex on disease manifestations and survival and confirms the early mortality in this disease.
Published: 2017

7. Nailfold Videocapillaroscopic Features and Other Clinical Risk Factors for Digital Ulcers in Systemic Sclerosis: A Multicenter, Prospective Cohort Study

Author: Cutolo, Maurizio, Herrick, Ariane L., Distler, Oliver, Becker, Mike O., Beltran, Emma, Carpentier, Patrick, Ferri, Clodoveo, Inanç, Murat, Vlachoyiannopoulos, Panayiotis, Chadha‐Boreham, Harbajan, Cottreel, Emmanuelle, Pfister, Thomas, Rosenberg, Daniel, Torres, Juan V., Smith, Vanessa, Becker, Mike, Erlacher, L, Hirschl, M, Kiener, HP, Pilger, E, Smith, V, Blockmans, D, Wautrecht, J‐C, Becvár, R, Carpentier, P, Frances, C, Lok, C, Sparsa, A, Hachulla, E, Quere, I, Allanore, Y, Agard, C, Riemekasten, G, Hunzelmann, N, Stücker, M, Ahmadi‐Simab, K, Sunderkötter, C, Wohlrab, J, Müller‐Ladner, U, Schneider, M, Vlachoyianopoulos, P, Vassilopoulos, D, Drosos, A, Antonopoulos, A, Balbir‐Gurman, A, Langevitz, P, Rosner, I, Levy, Y, Cutolo, M, Bombardieri, S, Ferraccioli, G, Mazzuca, S, Grassi, W, Lunardi, C, Airó, P, Riccieri, V, Voskuyl, AE, Schuerwegh, A, Santos, L, Rodrigues, AC, Grilo, A, Amaral, MC, Román Ivorra, JA, Castellvi, I, Distler, O, Spertini, F, Müller, R, Inanç, M, Oksel, F, Turkcapar, N, Herrick, A, Denton, C, McHugh, N, Chattopadhyay, C, Hall, F, Buch, M, University of Zurich, and Cutolo, Maurizio
Subjects: 0301 basic medicine, Male, EUSTAR DATABASE, Settore MED/16 - REUMATOLOGIA, RAYNAUDS-PHENOMENON, PREDICTION, 2745 Rheumatology, Logistic regression, Microscopic Angioscopy, Cohort Studies, 0302 clinical medicine, Risk Factors, Medicine and Health Sciences, Immunology and Allergy, Prospective Studies, Prospective cohort study, digital ulcers, systemic sclerosis, nailfold capillaroscopy, Peripheral Vascular Diseases, Digital Ulcers, 10051 Rheumatology Clinic and Institute of Physical Medicine, Area under the curve, VASCULAR-DISEASE, Middle Aged, MICROVASCULAR DAMAGE, 2723 Immunology and Allergy, digital ulcers, Rheumatology, Immunology, Female, medicine.symptom, SEVERE ORGAN INVOLVEMENT, Cohort study, Adult, PULMONARY ARTERIAL-HYPERTENSION, medicine.medical_specialty, nailfold capillaroscopy, 610 Medicine & health, CAPILLAROSCOPIC ANALYSIS, Systemic Sclerosis, Fingers, 03 medical and health sciences, Videocapillaroscopy, Digital Ulcers, Systemic Sclerosis, Scleroderma, Limited, Internal medicine, Skin Ulcer, medicine, Humans, Videocapillaroscopy, Aged, 030203 arthritis & rheumatology, 2403 Immunology, Scleroderma, Systemic, ENDOTHELIN RECEPTOR ANTAGONIST, Receiver operating characteristic, business.industry, Skin ulcer, Confidence interval, Surgery, 030104 developmental biology, ROC Curve, Observational study, EULAR SCLERODERMA TRIALS, business
Abstract: Objective To identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6-month period in patients with systemic sclerosis (SSc). Methods In this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) study, we evaluated 623 patients with SSc from 59 centers (14 countries). Patients were stratified into 2 groups: a DU history group and a no DU history group. At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and assessment of demographic characteristics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression (MLR) analyses. Results Of the 468 patients in the DU history group (mean ± SD age 54.0 ± 13.7 years), 79.5% were female, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow-up. The strongest risk factors for new DUs identified by MLR in the DU history group included the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs (categorized as 0, 1, 2, or ≥3), and the presence of critical digital ischemia. The receiver operating characteristic (ROC) of the area under the curve (AUC) of the final MLR model was 0.738 (95% confidence interval [95% CI] 0.681–0.795). Internal validation through bootstrap generated a ROC AUC of 0.633 (95% CI 0.510–0.756). Conclusion This international prospective study, which included detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc, identified the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs at enrollment, and the presence of critical digital ischemia at enrollment as risk factors for the development of new DUs.
Published: 2016

8. Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis. a 10-year longitudinal study from the EUSTAR database

Author: Wirz, E. G., Jaeger, V. K., Allanore, Y., Riemekasten, G., Hachulla, E., Distler, O., Airo, P., Carreira, P. E., Tikly, M., Vettori, S., Gurman, A. B., Damjanov, N., Muller-Ladner, U., Distler, J., Li, M., Hausermann, P., Walker, U. A., Ananieva, L., Heitmann, S., Rednic, S., Jimenez, S., Riccieri, V., Szmyrka-Kaczmarek, M., Farge, D., Lapadula, G., Matucci-Cerinic, M., Guiducci, S., Hunzelmann, N., Rosa Pozzi, M., Mihai, C., Veale, D., Hesselstrand, R., Mariok, E., Smith, V., Kucharz, E. J., Czirjak, L., Martinovic, D., Solanki, K., Mihaela Ancuta, C., Sibilia, J., Paola, C., Hassanien, M., Kahl, S., Woods, A., Vanthuyne, M., Ruxandra, I., Radominski, S. C., Lo Monaco, A., Corrado, A., Koehm, M., Maurizio, M., Radim, B., Loyo, E., Uprus, M., Pellerito, R., Zenone, T., Gabrielli, A., Kowal-Bielecka, O., Rozman, B., Scorza, R., Ann Saketkoo, L., Midtvedt, O., von Muhlen, C. A., Henes, J., Branimir, A., Hasler, P., Yavuz, S., Villiger, P., Krummel-Lorenz, B., Posa, M., Engelhart, M., Denton, C., Krasowska, D., de la Pena Lefebvre, P. G., Cozzi, F., Mouthon, L., Rosato, E., Carlo, S., Alegre Sancho, J. J., Mallia, C., Limonta, M., Seidel, M., Foti, R., Stamp, L., Ullman, S., Stebbings, S., Ortiz Santamaria, V., Del Galdo, F., De Langhe, E., Mathieu, A., Sunderkotter, C., Eyerich, K., Stamenkovic, B., Novak, S., Sampaio-Barros, P. D., Kayser, C., Litinsky, I., Couto, M., University of Zurich, Walker, U A, Wirz, Eg, Jaeger, Vk, Allanore, Y, Riemekasten, G, Hachulla, E, Distler, O, Airò, P, Carreira, Pe, Tikly, M, Vettori, Serena, Balbir Gurman, A, Damjanov, N, Müller Ladner, U, Distler, J, Li, M, Häusermann, P, Walker, Ua, and Eustar, Coauthors
Subjects: Male, Genetics and Molecular Biology (all), Pathology, Longitudinal study, Time Factors, Databases, Factual, Epidemiology, systemic sclerosis, 2745 Rheumatology, Kaplan-Meier Estimate, Severity of Illness Index, Biochemistry, Scleroderma, Risk Factors, Medizinische Fakultät, Immunology and Allergy, Longitudinal Studies, Prospective Studies, 610 Medicine & health, integumentary system, Incidence (epidemiology), Incidence, 10051 Rheumatology Clinic and Institute of Physical Medicine, Middle Aged, Connective tissue disease, 3. Good health, Autoantibodies, Systemic Sclerosis, Cohort, 2723 Immunology and Allergy, Female, Adult, medicine.medical_specialty, Immunology, General Biochemistry, Genetics and Molecular Biology, Sex Factors, Rheumatology, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Skin Ulcer, medicine, Humans, ddc:610, Proportional Hazards Models, 2403 Immunology, Scleroderma, Systemic, business.industry, medicine.disease, Clinical trial, Biochemistry, Genetics and Molecular Biology (all), Scleroderma, Diffuse, business
Abstract: Objectives To longitudinally map the onset and identify risk factors for skin sclerosis and digital ulcers (DUs) in patients with systemic sclerosis (SSc) from an early time point after the onset of Raynaud9s phenomenon (RP) in the European Scleroderma Trials and Research (EUSTAR) cohort. Methods 695 patients with SSc with a baseline visit within 1 year after RP onset were followed in the prospective multinational EUSTAR database. During the 10-year observation period, cumulative probabilities of cutaneous lesions were assessed with the Kaplan–Meier method. Cox proportional hazards regression analysis was used to evaluate risk factors. Results The median modified Rodnan skin score (mRSS) peaked 1 year after RP onset, and was 15 points. The 1-year probability to develop an mRSS ≥2 in at least one area of the arms and legs was 69% and 25%, respectively. Twenty-five per cent of patients developed diffuse cutaneous involvement in the first year after RP onset. This probability increased to 36% during the subsequent 2 years. Only 6% of patients developed diffuse cutaneous SSc thereafter. The probability to develop DUs increased to a maximum of 70% at the end of the 10-year observation. The main factors associated with diffuse cutaneous SSc were the presence of anti-RNA polymerase III autoantibodies, followed by antitopoisomerase autoantibodies and male sex. The main factor associated with incident DUs was the presence of antitopoisomerase autoantibodies. Conclusion Early after RP onset, cutaneous manifestations exhibit rapid kinetics in SSc. This should be accounted for in clinical trials aiming to prevent skin worsening.
Published: 2016

9. Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility

Author: Diaz-Gallo, L.M., Simeon, C.P., Broen, J.C.A., Ortego-Centeno, N., Beretta, L., Vonk, M.C., Carreira, P.E., Vargas, S., Roman-Ivorra, J.A., Gonzalez-Gay, M.A., Tolosa, C., Lopez-Longo, F.J., Espinosa, G., Vicente, E.F., Hesselstrand, R., Riemekasten, G., Witte, T. de, Distler, J.H., Voskuyl, A.E., Schuerwegh, A.J., Shiels, P.G., Nordin, A., Padyukov, L., Hoffmann-Vold, A.M., Scorza, R., Lunardi, C., Airo, P., Laar, J.M. van, Hunzelmann, N., Gathof, B.S., Kreuter, A., Herrick, A., Worthington, J., Denton, C.P., Zhou, X., Arnett, F.C., Fonseca, C., Koeleman, B.P., Assasi, S., Radstake, T.R.D.J., Mayes, M.D., Martin, J., Universitat de Barcelona, Rheumatology, and CCA - Immuno-pathogenesis
Subjects: Male, Genotype, systemic sclerosis, Autoimmune diseases, Immunology, Locus (genetics), Single-nucleotide polymorphism, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Article, White People, General Biochemistry, Genetics and Molecular Biology, GWAS, IL-2/IL-21 region, Gene Frequency, Rheumatology, Scleroderma, Limited, Medizinische Fakultät, Genetic variation, Genetics, Genetic predisposition, Humans, Immunology and Allergy, Genetic Predisposition to Disease, ddc:610, Allele, Allele frequency, Scleroderma, Systemic, Malalties autoimmunitàries, Interleukins, Logistic Models, Scleroderma (Disease), Case-Control Studies, Scleroderma, Diffuse, Interleukin-2, Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2], Female, Gene polymorphism, Esclerodèrmia, Genètica
Abstract: ObjectiveThe interleukin 2 (IL-2) and interleukin 21 (IL-21) locus at chromosome 4q27 has been associated with several autoimmune diseases, and both genes are related to immune system functions. The aim of this study was to evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc).Patients and methodsThe case control study included 4493 SSc Caucasian patients and 5856 healthy controls from eight Caucasian populations (Spain, Germany, The Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using TaqMan allelic discrimination assays.ResultsWe observed evidence of association of the rs6822844 and rs907715 variants with global SSc (pc=6.6E-4 and pc=7.2E-3, respectively). Similar statistically significant associations were observed for the limited cutaneous form of the disease. The conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs6822844 polymorphism. Consistently, the rs2069762A-rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of association with SSc and limited cutaneous SSc subtype (pc=1.7E-03 and pc=8E-4, respectively).ConclusionsThese results suggested that the IL-2/IL-21 locus influences the genetic susceptibility to SSc. Moreover, this study provided further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune diseases.
Published: 2012

10. Expert agreement on EULAR/EUSTAR recommendations for the management of systemic sclerosis

Author: Walker, Kyle M., Pope, Janet, Alkassab, F, Molitor, Ja, Shapiro, Ls, Fessler, Bj, Gran, Jt, Goldberg, A, Medsger, TA Jr, VALENTINI, Gabriele, Csuka, Me, Griffing, L, Herrick, A, Connolly, M, Vacca, A, Riemekasten, G, Wigley, Fm, Farge, D, Johnson, Sr, Matucci Cerinic, M, Czirjak, L, Toloza, Sm, Mahmud, Th, Frech, Tm, Voskuyl, Ae, Merkel, Pa, Domsic, R, Emery, P, Steen, V, Rudnicka, L, Denton, Cp, Clements, Pj, Chatterjee, S, Kahaleh, B, Hayat, S, Mouthon, L, Lafyatis, R, Lally, Ev, Krieg, T, Chung, L, Catoggio, Lj, Mayes, Md, Anderson, Me, Silver, R, Proudman, S, Seibold, Jr, Senécal, Jl, Stevens, W, Hachulla, E, Inanc, M, Wollheim, F, Distler, O, Katsumoto, Tr, Hsu, V, Collier, Dh, Furst, D, Mckown, K, Khanna, D, Volkov, S, Mathieu, A, Baron, M, Kaminska, Ea, Khalidi, Na, Hudson, M, Markland, J, Masetto, A, Docherty, P., Walker, Kyle M., Pope, Janet, Alkassab, F, Molitor, Ja, Shapiro, L, Fessler, Bj, Gran, Jt, Goldberg, A, Medsger, TA Jr, Valentini, Gabriele, Csuka, Me, Griffing, L, Herrick, A, Connolly, M, Vacca, A, Riemekasten, G, Wigley, Fm, Farge, D, Johnson, Sr, Matucci Cerinic, M, Czirjak, L, Toloza, Sm, Mahmud, Th, Frech, Tm, Voskuyl, Ae, Merkel, Pa, Domsic, R, Emery, P, Steen, V, Rudnicka, L, Denton, Cp, Clements, Pj, Chatterjee, S, Kahaleh, B, Hayat, S, Mouthon, L, Lafyatis, R, Lally, Ev, Krieg, T, Chung, L, Catoggio, Lj, Mayes, Md, Anderson, Me, Silver, R, Proudman, S, Seibold, Jr, Senécal, Jl, Stevens, W, Hachulla, E, Inanc, M, Wollheim, F, Distler, O, Katsumoto, Tr, Hsu, V, Collier, Dh, Furst, D, Mckown, K, Khanna, D, Volkov, S, Mathieu, A, Baron, M, Kaminska, Ea, Khalidi, Na, Hudson, M, Markland, J, Masetto, A, and Docherty, P.
Subjects: Canada, Scleroderma, Systemic, Hypertension, Pulmonary, Skin Disease, Immunology, Health Survey, Sulfonamide, Epoprostenol, Scleroderma, Europe, Systemic sclerosi, Methotrexate, Treatment Outcome, Rheumatology, North America, Vascular Disease, Practice Guidelines as Topic, Immunology and Allergy, Iloprost, Survey, Societies, Medical, Treatment guideline, Human
Abstract: Objective. The European League Against Rheumatism/EULAR Scleroderma Trials and Research group (EULAR/EUSTAR) has published recommendations for the management of systemic sclerosis (SSc). Members of the Scleroderma Clinical Trials Consortium and the Canadian Scleroderma Research Group were surveyed regarding their level of agreement with the recommendations. Methods. A survey containing the 14 EULAR/EUSTAR recommendations asked participants to indicate their level of agreement with each on a 10-point scale, from 0 (not at all) to 9 (completely agree). The survey was sent to 117 people, and 66 replies were received (56% response rate). Results. Exceptions to generally high agreement included the use of iloprost and bosentan for digital vasculopathy, methotrexate for skin involvement, and bosentan and epoprostenol for pulmonary arterial hypertension (PAH; all < 69% agreement, defined as ≥ 7 rating). Vasculopathy and PAH treatment had differences in agreement between North America and Europe (p < 0.006). Respondents who were EULAR/EUSTAR recommendation authors shared a similar level of agreement compared to those who were not, except for the use of proton pump inhibitors for the prevention of SSc-related gastroesophageal reflux disease, esophageal ulcers, and strictures. Conclusion. EULAR/EUSTAR recommendations were relatively well accepted among SSc experts. Overall reduced agreement may be due to the modest efficacy of some agents (such as methotrexate for the skin). Some regional disagreement is likely because of access differences. The Journal of Rheumatology Copyright © 2011. All rights reserved.
Published: 2011

11. Evidence for the contribution of the X chromosome to Systemic Sclerosis susceptibility: Association with the functional IRAK1 196Phe/532Ser haplotype

Author: DIEUDÉ P, BOUAZIZ M, GUEDJ M, RIEMEKASTEN G, AIRO P, MÜLLER M, CUSI D, MATUCCI, CERINIC M, MELCHERS I, KOENIG W, SALVI E, WICHMANN H, HACHULLA E, DIOT, E, HUNZELMANN N, CARAMASCHI P, MOUTHON L, RICCIERI V, DISTLER J, TARNER I, AVOUAC, J, MEYER O, KAHAN A, CHIOCCHIA G, BOILEAU C, ALLANORE Y., CUOMO, Giovanna, Dieudé, P, Bouaziz, M, Guedj, M, Riemekasten, G, Airo, P, Müller, M, Cusi, D, Matucci, Cerinic, M, Melchers, I, Koenig, W, Salvi, E, Wichmann, H, Cuomo, Giovanna, Hachulla, E, Diot, E, Hunzelmann, N, Caramaschi, P, Mouthon, L, Riccieri, V, Distler, J, Tarner, I, Avouac, J, Meyer, O, Kahan, A, Chiocchia, G, Boileau, C, Allanore, Y., INSERM U699, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Spedali Civili, Ludwig Maximilians University of Munich, University Hospital, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Università degli Studi di Milano [Milano] (UNIMI), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University Medical Center, Universität Ulm - Ulm University [Ulm, Allemagne], Department of Cardio-Thoracic and Respiratory Science, Second University of Naples, Naples, Italy, Université de Lille, Droit et Santé, Centre Hospitalier Régional Universitaire de Tours (CHRU de Tours), University of Cologne, Azienda Ospedaliera Universitaria Integrata, Université Paris Descartes - Paris 5 (UPD5), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Justus-Liebig-Universität Gießen (JLU), Université Paris Diderot - Paris 7 (UPD7), Inserm U1016, Paris Descartes University, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Ambroise Paré [AP-HP], Supported by the Agence Nationale de la Recherche (grant R070994KS), the Societe Francaise de Rhumatologie, the Association des Sclerodermiques de France, the Groupe Francais de Recherche sur la Sclerodermie, and INSERM. Unrestricted institutional support was provided by Pfizer. The German Network for Systemic Sclerosis was funded by the German Federal Ministry for Education and Research (grants 01 GM 0310 and 01 GM 0634 to Drs. Riemekasten, Melchers, Hunzelmann, and Tarner). The MONICA/KORA Augsburg studies were funded by the Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Neuherberg, Germany, with additional support provided by the German Federal Ministry of Education and Research, the German National Genome Research Network (NGFNPlus project, grant 01GS0834), the University of Ulm, and Ludwig-Maximilian University Munich (LMU innovative project, Munich Center of Health Sciences). The European Network for Genetic-Epidemiological Studies (HYPERGENES) was funded by the European Union (Seventh Framework Programme, HEALTH-F4-2007-201550). The sample analyzed in the present study was collected by the Milan group in collaboration with the Center of Transfusion Medicine, Cellular Therapy and Cryobiology, Foundation IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, and the Filarete Foundation.Dr. Distler has received consulting fees, speaking fees, and/or honoraria from Actelion, GlaxoSmithKline, BSP Pharma, and Celgene (less than $10,000 each)., Ludwig-Maximilians University [Munich] (LMU), Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Firenze = University of Florence (UniFI), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), and Justus-Liebig-Universität Gießen = Justus Liebig University (JLU)
Subjects: Adult, systemic sclerosis, genotype, Immunology, rheumatology, Biology, iraki haplotype, IRAK1 Haplotype, 03 medical and health sciences, 0302 clinical medicine, Germany, Genotype, Immunology and Allergy, Humans, genetics, Pharmacology (medical), Genetic Predisposition to Disease, interleukin-1 receptor-associated kinases, scleroderma, [INFO]Computer Science [cs], Allele, [MATH]Mathematics [math], skin and connective tissue diseases, X chromosome, 030304 developmental biology, Aged, 030203 arthritis & rheumatology, 0303 health sciences, Chromosomes, Human, X, Scleroderma, Systemic, Genetic heterogeneity, Haplotype, x chromosome, Genetic Variation, Odds ratio, Middle Aged, Confidence interval, IRAK1 protein, human, genetic risk-factor, nf-kappa-b, lupus-erythematosus, innate-immunity, disease, activation, variant, irf5, pathogenesis, 3. Good health, Xq28, Haplotypes, Italy, Case-Control Studies, Female, France
Abstract: Objective Several autoimmune disorders, including systemic sclerosis (SSc), are characterized by a strong sex bias. To date, it is not known whether genes on the sex chromosomes influence SSc susceptibility. Recently, an IRAK1 haplotype that contains the 196Phe functional variant (rs1059702), located on Xq28, was found to confer susceptibility to systemic lupus erythematosus (SLE). This study was undertaken to test for an association between SSc and the IRAK1 SLE risk haplotype. Methods We tested for an association with the IRAK1 SLE risk haplotype in a discovery set of 849 SSc patients and 625 controls. IRAK1 rs1059702 was further genotyped in a replication set, which included Caucasian women from Italy (493 SSc patients and 509 controls) and Germany (466 SSc patients and 1,083 controls). Results An association between the IRAK1 haplotype and SSc was detected in the discovery set. In both the discovery and replication sets, the rs1059702 TT genotype was found to be associated with specific SSc subsets, highlighting a potential contribution to disease severity. A meta-analysis provided evidence of an association of both the T allele and TT genotype with the overall disease, with an odds ratio (OR) of 1.20 and 95% confidence interval (95% CI) of 1.06–1.35 for the T allele (P = 0.003) and an OR of 1.49 and 95% CI of 1.06–2.10 for the TT genotype (P = 0.023). However, the most notable associations were observed with the diffuse cutaneous, anti–topoisomerase I antibody positive, and SSc-related fibrosing alveolitis subsets (OR 2.35 [95% CI 1.51–3.66], P = 1.56 × 10−4, OR 2.84 [95% CI 1.87–4.32], P = 1.07 × 10−6, and OR 2.09 [95% CI 1.35–3.24], P = 9.05 × 10−4, respectively). Conclusion Our study provides the first evidence of an association between IRAK1 and SSc, demonstrating that a sex chromosome gene directly influences SSc susceptibility and its phenotypic heterogeneity.
Published: 2011

12. Characteristics of joint involvement and relationships with systemic inflammation in systemic sclerosis: results from the EULAR Scleroderma Trial and Research Group (EUSTAR) database

Author: Avouac, Jerome, Walker, Ulrich, Tyndall, Alan, Kahan, André, Matucci Cerinic, Marco, Allanore, Yannick, Miniati, I., Müller, A., Iannone, F., Giacomelli, R., Distler, O., Becvar, R., Sierakowsky, S., Kowal Bielecka, O., Coelho, P., Cabane, J., Cutolo, M., Shoenfeld, Y., Rovensky, J., Riemekasten, G., Nicoara, I., Vlachoyiannopoulos, P., Caporali, R., Jiri, S., Inanc, M., Gorska, I. Zimmermann, Carreira, P., Novak, S., Czirjak, L., Ramos, F. Oliveira, Jendro, M., Chizzolini, C., Kucharz, E. J., Richter, J., Cozzi, F., Rozman, B., Mallia, C. M., Gabrielli, A., Farge, D., Kiener, H. P., Schöffel, D., Sticherling, M., Airo, P., Wollheim, F., Martinovic, D., Trotta, F., Hunzelmann, N., Jablonska, S., Reich, K., Bombardieri, S., Siakka, P., Pellerito, R., Bambara, L. M., Morovic Vergles, J., Denton, C., Hinrichs, R., Van Den Hoogen, F., Damjanov, N., Kötter, I., Ortiz, V., Heitmann, S., Krasowska, D., Seidel, M., Hasler, P., Van Laar, J. M., Kaltwasser, J. P., Foeldvari, I., Juan Mas, A., Bajocchi, G., Wislowska, M., Pereira Da Silva, J. A., Jacobsen, S., Worm, M., Graniger, W., Kuhn, A., Stankovic, A., Cossutta, R., Majdan, M., Rajcevska, L. Damjanovska, Tikly, M., Nasonov, E. L., Steinbrink, K., Herrick, A., Müller Ladner, U., Dinc, A., Scorza, R., Sondergaard, K., Indiveri, F., Nielsen, H., Szekanecz, Z., Silver, R. M., Antivalle, M., Espinosa, I. B., García De La Pena Lefebvre, P., Midtvedt, O., Launay, D., Valesini, F., Tuvik, P., Ionescu, R. M., Del Papa, N., Pinto, S., Wigley, F., Mihai, C., Capranu, M. Sinziana, Sunderkötter, C., Jun, J. B., Derk, C., Alhasani, S., Distler, J. H., Ton, E., Soukup, T., Seibold, J., Zeni, S., Nash, P., Mouthon, L., De Keyser, F., Duruöz, M. T., Cantatore, F. P., Strauss, G., Von Mülhen, C. A., Pozzi, M. R., Eyerich, K., Szechinski, J., Keiserman, M., Houssiau, F. A., Rom Ivorra, J. A., Krummel Lorenz, B., Aringer, M., Westhovens, R., Bellisai, F., Mayer, M., Stoeckl, F., Üprus, M., Volpe, A., Buslau, M., Yavuz, S., Granel, B., Feijó, A. Valderílio, Del Galdo, F., Popa, S., Zenone, T., Machado, X. Ricardo, Pileckyte, M., Stebbings, S., Mathieu, A., Tulli, A., Tourinho, T., Souza, R., Acayaba De Toledo, R., Stamp, L., Solanki, K., Veale, D., Neto, J. Francisco Marques, Bagnato, G. F., Loyo, E., Toloza, S., Li, M., Mohamed, W. Ahmed Abdel Atty, Cobankara, V., Olas, J., Salsano, F., Oksel, F., Tanaseanu, C. M., Foti, R., Ancuta, C., Vonk, M., Caramashi, P., Beretta, L., Balbir, A., Shine, B., Chiàla, A., Simic, K. Pasalic, Ghio, M., Stamenkovic, B., Rednic, S., Host, N., Hachulla, E., Furst, D. E., VALENTINI, Gabriele, Avouac, Jerome, Walker, Ulrich, Tyndall, Alan, Kahan, André, Matucci Cerinic, Marco, Allanore, Yannick, Miniati, I., Müller, A., Iannone, F., Giacomelli, R., Distler, O., Becvar, R., Sierakowsky, S., Kowal Bielecka, O., Coelho, P., Cabane, J., Cutolo, M., Shoenfeld, Y., Valentini, Gabriele, Rovensky, J., Riemekasten, G., Nicoara, I., Vlachoyiannopoulos, P., Caporali, R., Jiri, S., Inanc, M., Gorska, I. Zimmermann, Carreira, P., Novak, S., Czirjak, L., Ramos, F. Oliveira, Jendro, M., Chizzolini, C., Kucharz, E. J., Richter, J., Cozzi, F., Rozman, B., Mallia, C. M., Gabrielli, A., Farge, D., Kiener, H. P., Schöffel, D., Sticherling, M., Airo, P., Wollheim, F., Martinovic, D., Trotta, F., Hunzelmann, N., Jablonska, S., Reich, K., Bombardieri, S., Siakka, P., Pellerito, R., Bambara, L. M., Morovic Vergles, J., Denton, C., Hinrichs, R., Van Den Hoogen, F., Damjanov, N., Kötter, I., Ortiz, V., Heitmann, S., Krasowska, D., Seidel, M., Hasler, P., Van Laar, J. M., Kaltwasser, J. P., Foeldvari, I., Juan Mas, A., Bajocchi, G., Wislowska, M., Pereira Da Silva, J. A., Jacobsen, S., Worm, M., Graniger, W., Kuhn, A., Stankovic, A., Cossutta, R., Majdan, M., Rajcevska, L. Damjanovska, Tikly, M., Nasonov, E. L., Steinbrink, K., Herrick, A., Müller Ladner, U., Dinc, A., Scorza, R., Sondergaard, K., Indiveri, F., Nielsen, H., Szekanecz, Z., Silver, R. M., Antivalle, M., Espinosa, I. B., García De La Pena Lefebvre, P., Midtvedt, O., Launay, D., Valesini, F., Tuvik, P., Ionescu, R. M., Del Papa, N., Pinto, S., Wigley, F., Mihai, C., Capranu, M. Sinziana, Sunderkötter, C., Jun, J. B., Derk, C., Alhasani, S., Distler, J. H., Ton, E., Soukup, T., Seibold, J., Zeni, S., Nash, P., Mouthon, L., De Keyser, F., Duruöz, M. T., Cantatore, F. P., Strauss, G., Von Mülhen, C. A., Pozzi, M. R., Eyerich, K., Szechinski, J., Keiserman, M., Houssiau, F. A., Rom Ivorra, J. A., Krummel Lorenz, B., Aringer, M., Westhovens, R., Bellisai, F., Mayer, M., Stoeckl, F., Üprus, M., Volpe, A., Buslau, M., Yavuz, S., Granel, B., Feijó, A. Valderílio, Del Galdo, F., Popa, S., Zenone, T., Machado, X. Ricardo, Pileckyte, M., Stebbings, S., Mathieu, A., Tulli, A., Tourinho, T., Souza, R., Acayaba De Toledo, R., Stamp, L., Solanki, K., Veale, D., Neto, J. Francisco Marque, Bagnato, G. F., Loyo, E., Toloza, S., Li, M., Mohamed, W. Ahmed Abdel Atty, Cobankara, V., Olas, J., Salsano, F., Oksel, F., Tanaseanu, C. M., Foti, R., Ancuta, C., Vonk, M., Caramashi, P., Beretta, L., Balbir, A., Shine, B., Chiàla, A., Simic, K. Pasalic, Ghio, M., Stamenkovic, B., Rednic, S., Host, N., Hachulla, E., Furst, D. E., Chizzolini, Carlo, and Westhovens, Rene
Subjects: Male, Systemic disease, Databases, Factual, Cross-sectional study, Joint Diseases/etiology/pathology/physiopathology, Systemic inflammation, Joint involvement, Scleroderma, systemic sclrosis, systemic inflemmetion, joint involvement, Tendons, Systemic sclerosi, Scleroderma, Localized, 0302 clinical medicine, data base, Immunopathology, joint radiography, Immunology and Allergy, Joints/pathology, scleroderma, 030212 general & internal medicine, nuclear magnetic resonance imaging, Range of Motion, Articular, skin and connective tissue diseases, rheumatic disease, ddc:616, interstitial lung disease, Joint contracture, Clinical Trials as Topic, Synovitis, Inflammation/etiology/pathology/physiopathology, integumentary system, article, Tendons/pathology, Middle Aged, musculoskeletal system, cohort analysis, Connective tissue disease, priority journal, Joint, Synoviti, Systemic sclerosis, Female, medicine.symptom, Joint Diseases, Human, musculoskeletal diseases, Adult, medicine.medical_specialty, hand radiography, Immunology, Scleroderma, Localized/etiology/*pathology, Auto-immunity, transplantation and immunotherapy [N4i 4], 03 medical and health sciences, SYSTEMIC SCLEROSIS, JOINT INVOLVEMENT, SYNOVITIS, JOINT CONTRACTURE, TENDON FRICTION RUB, Tendon friction rub, Rheumatology, Internal medicine, medicine, Humans, Health care ethics [NCEBP 5], Tendon, Aged, 030203 arthritis & rheumatology, Cross-Sectional Studie, Inflammation, skin disease, Scleroderma, Systemic, business.industry, echography, medicine.disease, major clinical study, tenosynovitis, Synovitis/etiology/pathology, clinical feature, body regions, Cross-Sectional Studies, Evaluation of complex medical interventions [NCEBP 2], Scleroderma, Systemic/complications/pathology/physiopathology, Joints, disease duration, business, Joint Disease, disease activity
Abstract: Objective.To determine the prevalence of and independent factors associated with joint involvement in a large population of patients with systemic sclerosis (SSc).Methods.This study was cross-sectional, based on data collected on patients included in the European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) registry. We queried this database to extract data regarding global evaluation of patients with SSc and the presence of any clinical articular involvement: synovitis (tender and swollen joints), tendon friction rubs (rubbing sensation detected as the tendon was moved), and joint contracture (stiffness of the joints that decreased their range of motion). Overall joint involvement was defined by the occurrence of synovitis and/or joint contracture and/or tendon friction rubs.Results.We recruited 7286 patients with SSc; their mean age was 56 ± 14 years, disease duration 10 ± 9 years, and 4210 (58%) had a limited cutaneous disease subset. Frequencies of synovitis, tendon friction rubs, and joint contractures were 16%, 11%, and 31%, respectively. Synovitis, tendon friction rubs, and joint contracture were more prevalent in patients with the diffuse cutaneous subset and were associated together and with severe vascular, muscular, renal, and interstitial lung involvement. Moreover, synovitis had the highest strength of association with elevated acute-phase reactants taken as the dependent variable.Conclusion.Our results highlight the striking level of articular involvement in SSc, as evaluated by systematic examination in a large cohort of patients with SSc. Our data also show that synovitis, joint contracture, and tendon friction rubs are associated with a more severe disease and with systemic inflammation.
Published: 2010

13. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database

Author: Tyndall, A. J., Bannert, B., Vonk, M., Airo, P., Cozzi, F., Carreira, P. E., Bancel, D. F., Allanore, Y., Muller Ladner, U., Distler, O., Iannone, F., Pellerito, R., Pileckyte, M., Miniati, I., Ananieva, L., Gurman, A. B., Damjanov, N., Mueller, A., Valentini, G., Riemekasten, G., Tikly, M., Hummers, L., Henriques, M. J. S., Caramaschi, P., Scheja, A., Rozman, B., Ton, E., Kumanovics, G., Coleiro, B., Feierl, E., Szucs, G., Von Muhlen, C. A., Riccieri, Valeria, Novak, S., Chizzolini, C., Kotulska, A., Denton, C., Coelho, P. C., Kotter, I., Simsek, I., La Pena, D. E., Lefebvre, P. G. D. L. P., Hachulla, E., Seibold, J. R., Rednic, S., Stork, J., Morovic Vergles, J., Walker, U. A., Tyndall, Aj, Bannert, B, Vonk, M, Airò, P, Cozzi, F, Carreira, Pe, Bancel, Df, Allanore, Y, MÜLLER LADNER, U, Distler, O, Iannone, F, Pellerito, R, Pileckyte, M, Miniati, I, Ananieva, L, Gurman, Ab, Damjanov, N, Mueller, A, Valentini, Gabriele, Riemekasten, G, Tikly, M, Hummers, L, Henriques, Mj, Caramaschi, P, Scheja, A, Rozman, B, Ton, E, Kumánovics, G, Coleiro, B, Feierl, E, Szucs, G, VON MÜHLEN, Ca, Riccieri, V, Novak, S, Chizzolini, C, Kotulska, A, Denton, C, Coelho, Pc, Kötter, I, Simsek, I, DE LA PENA LEFEBVRE, Pg, Hachulla, E, Seibold, Jr, Rednic, S, Stork, J, MOROVIC VERGLES, J, and Walker, Ua
Subjects: Lung Diseases, systemic sclreosis, risk factors, Male, Lung Diseases/mortality, Comorbidity, 030204 cardiovascular system & hematology, 0302 clinical medicine, Neoplasms, Epidemiology, Pulmonary fibrosis, Immunology and Allergy, skin and connective tissue diseases, Cause of death, ddc:616, integumentary system, Interstitial lung disease, Sepsis/mortality, Middle Aged, Prognosis, 3. Good health, Pneumonia/mortality, Cohort, Female, Neoplasms/mortality, Gastrointestinal Hemorrhage, Scleroderma, Systemic/*mortality, Adult, medicine.medical_specialty, Heart Diseases, Immunology, Auto-immunity, transplantation and immunotherapy [N4i 4], General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Rheumatology, Sepsis, Internal medicine, medicine, Humans, Gastrointestinal Hemorrhage/mortality, Risk factor, Health care ethics [NCEBP 5], Aged, 030203 arthritis & rheumatology, Scleroderma, Systemic, business.industry, Proportional hazards model, Heart Diseases/mortality, Pneumonia, medicine.disease, Surgery, Evaluation of complex medical interventions [NCEBP 2], Heart failure, business, Epidemiologic Methods
Abstract: Item does not contain fulltext OBJECTIVES: To determine the causes and predictors of mortality in systemic sclerosis (SSc). METHODS: Patients with SSc (n=5860) fulfilling the American College of Rheumatology criteria and prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. EUSTAR centres completed a structured questionnaire on cause of death and comorbidities. Kaplan-Meier and Cox proportional hazards models were used to analyse survival in SSc subgroups and to identify predictors of mortality. RESULTS: Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths, 35% were attributed to pulmonary fibrosis, 26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the non-SSc-related causes, infections (33%) and malignancies (31%) were followed by cardiovascular causes (29%). Of the non-SSc-related fatalities, 25% died of causes in which SSc-related complications may have participated (pneumonia, sepsis and gastrointestinal haemorrhage). Independent risk factors for mortality and their HR were: proteinuria (HR 3.34), the presence of PAH based on echocardiography (HR 2.02), pulmonary restriction (forced vital capacity below 80% of normal, HR 1.64), dyspnoea above New York Heart Association class II (HR 1.61), diffusing capacity of the lung (HR 1.20 per 10% decrease), patient age at onset of Raynaud's phenomenon (HR 1.30 per 10 years) and the modified Rodnan skin score (HR 1.20 per 10 score points). CONCLUSION: Disease-related causes, in particular pulmonary fibrosis, PAH and cardiac causes, accounted for the majority of deaths in SSc. 01 oktober 2010
Published: 2010

14. Reconciling Healthcare Professional and Patient Perspectives in the Development of Disease Activity and Response Criteria in Connective Tissue Disease Related Interstitial Lung Diseases

Author: Saketkoo, La, Mittoo, S, Frankel, S, Lesage, D, Sarver, C, Phillips, K, Strand, V, Matteson, El, OMERACT Baughman RP, Brown, Kk, Christmann, Rb, Dellaripa, P, Denton, Cp, Distler, O, Fischer, A, Flaherty, K, Huscher, D, Khanna, D, Kowal Bielecka, O, Merkel, Pa, Oddis, Cv, Pittrow, D, Sandorfi, N, Seibold, Jr, Swigris, J, Wells, A, Antoniou, K, Castelino, Fv, Christopher Stine, L, Collard, Hr, Cottin, V, Danoff, S, Hedlund, R, Highland, Kb, Hummers, L, Lynch, Da, Kim, Ds, Ryu, Jh, Miller, Fw, Nichols, K, Proudman, Sm, Richeldi, L, Shah, Aa, van den Assum, P, Aggarwal, R, Ainslie, G, Alkassab, F, Allanore, Y, Anderson, Me, Andonopoulos, Ap, Antin Ozerkis, D, Arrobas, A, Ascherman, Dp, Assassi, S, Baron, M, Bathon, Jm, Baughman, Rp, Behr, J, Beretta, L, Bingham, Co, Binnie, M, Birring, Ss, Boin, F, Bongartz, T, Bourdin, A, Bouros, D, Brasington, R, Bresser, P, Buch, Mh, Burge, Ps, Carmona, L, Carreira, Pe, Carvalho, Cr, Catoggio, Lj, Chan, Km, Chapman, J, Chatterjee, S, Chua, F, Chung, L, Conron, M, Corte, T, Cosgrove, G, Costabel, U, Cox, G, Crestani, B, Crofford, Lj, Csuka, Me, Curbelo, P, Czirják, L, Daniil, Z, D'Arsigny, Cl, Davis, Gs, de Andrade JA, Dellaripa, Pf, De Vuyst, P, Dempsey, Oj, Derk, Ct, Distler, J, Dixon, Wg, Downey, G, Doyle, Mk, Drent, M, Durairaj, L, Emery, P, Espinoza, Lr, Farge, D, Fathi, M, Fell, Cd, Fessler, Bj, Fitzgerald, Je, Flaherty, Kr, Foeldvari, I, Fox, Ga, Frech, Tm, Freitas, S, Furst, De, Gabrielli, A, García Vicuña, R, Georgiev, Ob, Gerbino, A, Gillisen, A, Gladman, Dd, Glassberg, M, Gochuico, Br, Gogali, A, Goh, Ns, Goldberg, A, Goldberg, Hj, Gourley, Mf, Griffing, L, Grutters, Jc, Gunnarsson, R, Hachulla, E, Hall, Fc, Harari, S, Herrick, Al, Herzog, El, Hesselstrand, R, Highland, K, Hirani, N, Hodgson, U, Hollingsworth, Hm, Homer, Rj, Hoyles, Rk, Hsu, Vm, Hubbard, Rb, Hunzelmann, N, Isasi, Me, Isasi, Es, Jacobsen, S, Jimenez, Sa, Johnson, Sr, Jones, Ch, Kahaleh, B, Kairalla, Ra, Kalluri, M, Kalra, S, Kaner, Rj, Kinder, Bw, Kiter, G, Klingsberg, Rc, Kokosi, M, Kolb, Mr, Kowal Bielecka OM, Kur Zalewska, J, Kuwana, M, Lake, Fr, Lally, Ev, Lasky, Ja, Laurindo, Im, Able, L, Lee, P, Leonard, Ct, Lien, Dc, Limper, Ah, Liossis, Sn, Lohr, Km, Loyd, Je, Lundberg, Ie, Mageto, Yn, Maher, Tm, Mahmud, Th, Manganas, H, Marie, I, Marras, Tk, Martinez, Ja, Martinez, Fj, Mathieu, A, Matucci Cerinic, M, Mayes, Md, Mckown, Km, Medsger, Ta, Meehan, Rt, Mendes, Ac, Meyer, Kc, Millar, Ab, Moğulkoc, N, Molitor, Ja, Morais, A, Mouthon, L, Müller, V, Müller Quernheim, J, Nadashkevich, O, Nador, R, Nash, P, Nathan, Sd, Navarro, C, Neves, S, Noth, I, Nunes, H, Olson, Al, Opitz, Cf, Padilla, M, Pappas, D, Parfrey, H, Pego Reigosa JM, Pereira, Ca, Perez, R, Pope, Je, Porter, Jc, Renzoni, Ea, Riemekasten, G, Riley, Dj, Rischmueller, M, Rodriguez Reyna TS, Rojas Serrano, J, Roman, J, Rosen, Gd, Rossman, M, Rothfield, N, Sahn, Sa, Sanduzzi, A, Scholand, Mb, Selman, M, Senécal, Jl, Seo, P, Shah, A, Silver, Rm, Solomon, Jj, Steen, V, Stevens, W, Strange, C, Sussman, R, Sutton, Ed, Sweiss, Nj, Tornling, G, Tzelepis, Ge, Undurraga, A, Vacca, A, Vancheri, Carlo, Varga, J, Veale, Dj, Volkov, S, Walker, Ua, Wells, Au, Wencel, M, Wesselius, Lj, Wickremasinghe, M, Wilcox, P, Wilsher, Ml, Wollheim, Fa, Wuyts, Wa, Yung, G, Zanon, P, Zappala, Cj, Groshong, Sd, Leslie, Ko, Myers, Jl, Padera, Rf, Desai, Sr, Goldin, J, Kazerooni, Ea, Klein, Js, and Keen, Kj
Subjects: Male, medicine.medical_specialty, Delphi Technique, Consensus Development Conferences as Topic, Health Personnel, Immunology, Context (language use), Disease, Severity of Illness Index, Article, Idiopathic pulmonary fibrosis, Rheumatology, medicine, Immunology and Allergy, Humans, Disease management (health), Intensive care medicine, Connective Tissue Diseases, Randomized Controlled Trials as Topic, business.industry, Interstitial lung disease, Disease Management, respiratory system, Focus Groups, medicine.disease, Comorbidity, Connective tissue disease, respiratory tract diseases, Clinical trial, Treatment Outcome, Patient Satisfaction, Physical therapy, Quality of Life, ÍNDICE DE GRAVIDADE DA DOENÇA, Interdisciplinary Communication, business, Lung Diseases, Interstitial
Abstract: Interstitial lung diseases (ILD), including those related to connective tissue disease (CTD), and idiopathic pulmonary fibrosis (IPF) carry high morbidity and mortality. Great efforts are under way to develop and investigate meaningful treatments in the context of clinical trials. However, efforts have been challenged by a lack of validated outcome measures and by inconsistent use of measures in clinical trials. Lack of consensus has fragmented effective use of strategies in CTD-ILD and IPF, with a history of resultant difficulties in obtaining agency approval of treatment interventions. Until recently, the patient perspective to determine domains and outcome measures in CTD-ILD and IPF had never been applied. Efforts described here demonstrate unequivocally the value and influence of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/comorbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF.
Published: 2014

15. Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the EUSTAR database

Author: Maurer, B., Graf, N., Michel, B. A., Muller Ladner, U., Czirjak, L., Denton, C. P., Tyndall, A., Metzig, C., Lanius, V., Khanna, D., Distler, O., Arner, I. H., Cerinic, M. M., Guiducci, S., Walker, U., Lapadula, G., Iannone, F., Becvar, R., Sierakowsky, S., Bielecka, O. K., Cutolo, M., Sulli, A., Valentini, G., Cuomo, G., Vettori, S., Riemekasten, G., Rednic, S., Nicoara, I., Kahan, A., Allanore, Y., Vlachoyiannopoulos, P., Montecucco, C., Caporali, R., Carreira, P. E., Novak, S., Varju, C., Chizzolini, C., Kucharz, E. J., Kotulska, A., Kopec Medrek, M., Widuchowska, M., Cozzi, F., Rozman, B., Mallia, C., Coleiro, B., Gabrielli, A., Farge, D., Hij, A., Airo, P., Hesselstrand, R., Scheja, A., Wollheim, F., Martinovic, D., Gurman, A. B., Braun Moscovici, Y., Govoni, Marcello, LO MONACO, Andrea, Hunzelmann, N., Pellerito, R., Bambara, L. M., Caramaschi, P., Black, C., Damjanov, N., Santamaria, V. O., Heitmann, S., Krasowska, D., Seidel, M., Oleszowsky, M., Burkhardt, H., Himsel, A., Salvador, M. J., Stamenkovic, B., Stankovic, A., Tikly, M., Starovoytova, M. N., Ananieva, L. P., Scorza, R., Engelhart, M., Strauss, G., Nielsen, H., Damgaard, K., Szucs, G., Mendoza, A. Z., Buijdos, C. d. l. P., Sifuentes Giraldo, W. A., Midtvedt, O., Garen, T., Hachulla, E., Launay, D., Valesini, G., Riccieri, V., Ionescu, R. M., Opris, D., Groseanu, L., Wigley, F. M., Mihai, C. M., Cornateanu, R. S., Ionitescu, R., Gherghe, A. M., Gorga, M., Dobrota, R., Bojinca, M., Schett, G., Distler, J. H., Meroni, P., Zeni, P., Mouthon, L., Keyser, F. D., Cantatore, F. P., Corrado, A., Ullman, S., Iversen, L., Pozzi, M. R., Eyerich, K., Hein, R., Knott, E., Szechinski, J., Wiland, P., Szmyrka Kaczmarek, M., Sokolik, R., Morgiel, E., Krummel Lorenz, B., Saar, P., Aringer, M., Gunther, C., Anic, B., Baresic, M., Mayer, M., Radominski, S. C., Muller, C. d. S., Azevedo, V. F., Agachi, S., Groppa, L., Chiaburu, L., Russu, E., Zenone, T., Highton, J., Stamp, L., Chapman, P., O'Donnell, J., Solanki, K., Doube, A., Veale, D., O'Rourke, M., Loyo, E., Li, M., Rosato, E., Pisarri, S., Tanaseanu, C. M., Popescu, M., Dumitrascu, A., Tiglea, I., Chirieac, R., Ancuta, C., Furst, D. E., Kafaja, S., Lefebvre, P. G. d. l. P., Rubio, S. R., Exposito, M. V., Sibilia, J., Chatelus, E., Gottenberg, J. E., Chifflot, H., Litinsky, I., Venalis, A., Butrimiene, I., Venalis, P., Rugiene, R., Karpec, D., Kerzberg, E., Montoya, F., Cosentino, V., Chizzolini, Carlo, Maurer, Britta, Graf, Nicole, Michel, Beat A, Müller Ladner, Ulf, Czirják, László, Denton, Christopher P, Tyndall, Alan, Metzig, Carola, Lanius, Vivian, Khanna, Dinesh, Distler, Oliver, Tarner, Ingo H, Cerinic, Marco Matucci, Guiducci, Serena, Walker, Ulrich, Lapadula, Giovanni, Iannone, Florenzo, Becvar, Radim, Sierakowsky, Stanislaw, Bielecka, Otylia Kowal, Cutolo, Maurizio, Sulli, Alberto, Valentini, Gabriele, Cuomo, Giovanna, Vettori, Serena, Riemekasten, Gabriele, Rednic, Simona, Nicoara, Ileana, Kahan, André, Allanore, Yannick, Vlachoyiannopoulos, P, Montecucco, Carlomaurizio, Caporali, Roberto, Carreira, Patricia E, Novak, Srdan, Varju, Cecilia, Kucharz, Eugene J, Kotulska, Anna, Kopec Medrek, Magdalena, Widuchowska, Malgorzata, Cozzi, Franco, Rozman, Blaz, Mallia, Carmel, Coleiro, Bernard, Gabrielli, Armando, Farge, Dominique, Hij, Adrian, Airò, Paolo, Hesselstrand, Roger, Scheja, Agneta, Wollheim, Frank, Martinovic, Duska, Gurman, Alexandra Balbir, Braun Moscovici, Yolanda, Govoni, M, Monaco, Andrea Lo, Hunzelmann, Nicola, Pellerito, Raffaele, Bambara, Lisa Maria, Caramaschi, Paola, Black, Carol, Damjanov, Nemanja, Santamaria, Vera Ortiz, Heitmann, Stefan, Krasowska, Dorota, Seidel, Matthia, Oleszowsky, Mara, Burkhardt, Harald, Himsel, Andrea, Salvador, Maria J, Stamenkovic, Bojana, Stankovic, Aleksandra, Tikly, Mohammed, Starovoytova, Maya N, Ananieva, Lidia P, Scorza, Raffaella, Engelhart, Merete, Strauss, Gitte, Nielsen, Henrik, Damgaard, Kirsten, Szücs, Gabriella, Mendoza, Antonio Zea, Buijdos, Carlos de la Puente, Giraldo, Walter A. Sifuente, Midtvedt, Øyvind, Garen, Torhild, Hachulla, Eric, Launay, David, Valesini, Guido, Riccieri, Valeria, Ionescu, Ruxandra Maria, Opris, Daniela, Groseanu, Laura, Wigley, Fredrick M, Mihai, Carmen M, Cornateanu, Roxana Sfrent, Ionitescu, Razvan, Gherghe, Ana Maria, Gorga, Marilena, Dobrota, Rucsandra, Bojinca, Mihai, Schett, Georg, Distler, Jörg HW, Meroni, Pierluigi, Zeni, Silvana, Mouthon, Luc, Keyser, Filip De, Cantatore, Francesco P, Corrado, Ada, Ullman, Susanne, Iversen, Line, Pozzi, Maria R, Eyerich, Kilian, Hein, Rüdiger, Knott, Elisabeth, Szechinski, Jacek, Wiland, Piotr, Szmyrka Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Krummel Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Günther, Claudia, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Radominski, Sebastião C, Müller, Carolina de Souza, Azevedo, Valderílio F, Agachi, Svetlana, Groppa, Liliana, Chiaburu, Lealea, Russu, Eugen, Zenone, Thierry, Highton, John, Stamp, Lisa, Chapman, Peter, O'Donnell, John, Solanki, Kamal, Doube, Alan, Veale, Dougla, O’Rourke, Marie, Loyo, Esthela, Li, Mengtao, Rosato, Edoardo, Pisarri, Simonetta, Tanaseanu, Cristina Mihaela, Popescu, Monica, and University of Zurich
Subjects: Genetics and Molecular Biology (all), Male, Time Factors, Databases, Factual, systemic sclerosis, 2745 Rheumatology, computer.software_genre, Biochemistry, Severity of Illness Index, Outcomes Research, Qualitative Research, Systemic Sclerosis, Adult, Cohort Studies, Creatine Kinase, Decision Support Techniques, Deglutition Disorders, Dyspnea, Female, Fibrosis, Humans, Logistic Models, Middle Aged, Multivariate Analysis, Scleroderma, Diffuse, Sex Factors, Skin, Synovitis, Disease Progression, Rheumatology, Immunology, Biochemistry, Genetics and Molecular Biology (all), Immunology and Allergy, Medicine (all), Scleroderma, skin fibrosis, skin and connective tissue diseases, ddc:616, EUSTAR, Univariate analysis, Database, integumentary system, 10051 Rheumatology Clinic and Institute of Physical Medicine, Orvostudományok, Diffuse, Connective tissue disease, Cohort, 2723 Immunology and Allergy, Cohort study, medicine.medical_specialty, 610 Medicine & health, Klinikai orvostudományok, General Biochemistry, Genetics and Molecular Biology, NO, outcomes research, qualitative research, Databases, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Severity of illness, medicine, Factual, 2403 Immunology, business.industry, medicine.disease, business, computer
Abstract: ObjectivesTo identify predictive parameters for the progression of skin fibrosis within 1 year in patients with diffuse cutaneous SSc (dcSSc).MethodsAn observational study using the EUSTAR database was performed. Inclusion criteria were dcSSc, American College of Rheumatology (ACR) criteria fulfilled, modified Rodnan skin score (MRSS) ≥7 at baseline visit, valid data for MRSS at 2nd visit, and available follow-up of 12±2 months. Worsening of skin fibrosis was defined as increase in MRSS >5 points and ≥25% from baseline to 2nd visit. In the univariate analysis, patients with progressive fibrosis were compared with non-progressors, and predictive markers with pResultsA total of 637 dcSSc patients were eligible. Univariate analyses identified joint synovitis, short disease duration (≤15 months), short disease duration in females/patients without creatine kinase (CK) elevation, low baseline MRSS (≤22/51), and absence of oesophageal symptoms as potential predictors for progressive skin fibrosis. In the multivariate analysis, by employing combinations of the predictors, 17 models with varying prediction success were generated, allowing cohort enrichment from 9.7% progressive patients in the whole cohort to 44.4% in the optimised enrichment cohort. Using a second validation cohort of 188 dcSSc patients, short disease duration, low baseline MRSS and joint synovitis were confirmed as independent predictors of progressive skin fibrosis within 1 year resulting in a 4.5-fold increased prediction success rate.ConclusionsOur study provides novel, evidence-based criteria for the enrichment of dcSSc cohorts with patients who experience worsening of skin fibrosis which allows improved clinical trial design.
Published: 2014

16. Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database

Author: Walker U. A., Tyndall A., Czirják L, Denton C. ., Farge Bancel D., Kowal Bielecka O., Müller Ladner U., Bocelli Tyndall C., Matucci Cerinic M., Riemekasten G. ., Brückner C. ., Airó P. ., Scarsi M. ., Scorza R. ., Beretta L. ., Cozzi F. ., Tiso F., Vonk Mc M. C., Hoogen Van Den, Fhj F. H. J., Wigley Fm F. M., Hummers L. ., Nevskaya T. ., Ananieva L. ., Miniati I. ., Tartaglia N. ., Lomater C. ., Balbir Gurman A. ., Braun Moscovici Y. ., Bambara Lm L. M., Caramaschi P. ., Ruocco L. ., Krieg T. ., Hunzelmann N. ., Varjú C. ., Carriera Pe P. E., Joven B. ., Iannone F. ., Lapadula G. ., Kahan A. ., Allanore Y. ., Gabrielli A. ., Imperatore M. ., Scheja A. ., Wollheim F. ., Damjanov N. ., Ostojic P. ., Saar P. ., Tarner Ih I. H., Kötter I. ., Bombardieri S. ., Bazzichi L. ., Papa Del N. ., Comina Dp D. P., Monaco Lo A. ., Corte La R. ., Hachulla E. ., Launay D. ., Distler O. ., Ciurea A. ., Sierakowski S. ., Mitchell H. ., Silver Rm R. M., Krasowska D. ., Michalska Jakubus M. ., Tikly M. ., Aboo N. ., Worm M. ., Klaus P. ., Rovenský J. ., Lukáčová O. ., Rozman B. ., Sipek A. ., Clemente Coelho P. ., Shoenfeld Y. ., Langewitch P. ., José Da Silva Ap A. P., Salvador Mj M. J., Kuhn A. ., Erdmann G. ., Bečvář R. ., Friedl E. ., Graninger W. ., Riccieri V. ., Caporali R. ., Montecucco C. ., Vlachoyiannopoulos P. ., Distler M. ., Reich K. ., Majdan M. ., Wielosz E. ., Rednic S. ., Laar Van Jm J. M., Heitmann S. ., Bruckner A. ., Himsel A. ., Riemann J. ., Meyringer R. ., Müller A. ., Martinovic D. ., Radic M. ., Sticherling M. ., Szekanecz Z. ., Szücs G. ., Giacomelli R. ., Marrelli A. ., Stamenkovic B. ., Stankovic A. ., Aringer M. ., Smolen Js J. S., Kucharz Ej E. J., Kotulska At A. T., Jablonska S. ., Blasczik M. ., Jun J. B. J. B., Mallia C. ., Coleiro B. ., Santamaria Vo V. O., Hinrichs R. ., Nielsen H. ., Cossutta R. ., Ionescu R. ., Opris D. ., Steinbrink K. ., Grundt B. ., Bajocchi G. ., Jiří Š. ., Lefebvre Pgdlp P. G. D. L. P., Mendoza ZeaAc A. C., Ribi C. ., Chizzolini C. ., Wisłowska M. ., Novak S. ., Indiveri F. ., Jacobsen S. ., Frandsen Pb P. B., Gorska Iz I. Z., Gran Tore J. ., Midtvedt Ø. ., Ramos Fo F. O., Rajcevska Ld L. D., Bozinovski G. ., Schöffel D. ., Sunderkötter C. ., Böhm M. ., Morović Vergles J. ., Čulo M. I. M. I., Cutolo M. ., Sulli A. ., Derk Ct C. T., Jimenez Sa S. A., Siakka P. ., Søndergaard K. ., Stengaard Pedersen K. ., Cabane J. ., Tiev Kp K. P., Mihai C. ., Sfrent Cornateanu R. ., Jendro M. ., Tuvik P. ., Antivalle M. ., Randisi G. ., Seidel M. ., Clarenbach R. ., Simsek I. ., Dinc A. ., Inanc M. ., Capraru Ms M. S., Capraru D. ., Bañegil I. ., Richter J. ., Alhasani S. ., Földvari I. ., Pinto S. ., Brandão F. ., VALENTINI, Gabriele, Walker, U. A., Tyndall, A., Czirják, L, Denton, C. ., Farge Bancel, D., Kowal Bielecka, O., Müller Ladner, U., Bocelli Tyndall, C., Matucci Cerinic, M., Riemekasten, G. ., Brückner, C. ., Airó, P. ., Scarsi, M. ., Scorza, R. ., Beretta, L. ., Cozzi, F. ., Tiso, F., Vonk Mc, M. C., Hoogen Van, Den, Fhj, F. H. J., Wigley Fm, F. M., Hummers, L. ., Nevskaya, T. ., Ananieva, L. ., Miniati, I. ., Tartaglia, N. ., Lomater, C. ., Balbir Gurman, A. ., Braun Moscovici, Y. ., Bambara Lm, L. M., Caramaschi, P. ., Valentini, Gabriele, Ruocco, L. ., Krieg, T. ., Hunzelmann, N. ., Varjú, C. ., Carriera Pe, P. E., Joven, B. ., Iannone, F. ., Lapadula, G. ., Kahan, A. ., Allanore, Y. ., Gabrielli, A. ., Imperatore, M. ., Scheja, A. ., Wollheim, F. ., Damjanov, N. ., Ostojic, P. ., Saar, P. ., Tarner Ih, I. H., Kötter, I. ., Bombardieri, S. ., Bazzichi, L. ., Papa Del, N. ., Comina Dp, D. P., Monaco Lo, A. ., Corte La, R. ., Hachulla, E. ., Launay, D. ., Distler, O. ., Ciurea, A. ., Sierakowski, S. ., Mitchell, H. ., Silver Rm, R. M., Krasowska, D. ., Michalska Jakubus, M. ., Tikly, M. ., Aboo, N. ., Worm, M. ., Klaus, P. ., Rovenský, J. ., Lukáčová, O. ., Rozman, B. ., Sipek, A. ., Clemente Coelho, P. ., Shoenfeld, Y. ., Langewitch, P. ., José Da Silva Ap, A. P., Salvador Mj, M. J., Kuhn, A. ., Erdmann, G. ., Bečvář, R. ., Friedl, E. ., Graninger, W. ., Riccieri, V. ., Caporali, R. ., Montecucco, C. ., Vlachoyiannopoulos, P. ., Distler, M. ., Reich, K. ., Majdan, M. ., Wielosz, E. ., Rednic, S. ., Laar Van Jm, J. M., Heitmann, S. ., Bruckner, A. ., Himsel, A. ., Riemann, J. ., Meyringer, R. ., Müller, A. ., Martinovic, D. ., Radic, M. ., Sticherling, M. ., Szekanecz, Z. ., Szücs, G. ., Giacomelli, R. ., Marrelli, A. ., Stamenkovic, B. ., Stankovic, A. ., Aringer, M. ., Smolen Js, J. S., Kucharz Ej, E. J., Kotulska At, A. T., Jablonska, S. ., Blasczik, M. ., Jun, J. B. J. B., Mallia, C. ., Coleiro, B. ., Santamaria Vo, V. O., Hinrichs, R. ., Nielsen, H. ., Cossutta, R. ., Ionescu, R. ., Opris, D. ., Steinbrink, K. ., Grundt, B. ., Bajocchi, G. ., Jiří, Š. ., Lefebvre Pgdlp, P. G. D. L. P., Mendoza ZeaAc, A. C., Ribi, C. ., Chizzolini, C. ., Wisłowska, M. ., Novak, S. ., Indiveri, F. ., Jacobsen, S. ., Frandsen Pb, P. B., Gorska Iz, I. Z., Gran Tore, J. ., Midtvedt, Ø. ., Ramos Fo, F. O., Rajcevska Ld, L. D., Bozinovski, G. ., Schöffel, D. ., Sunderkötter, C. ., Böhm, M. ., Morović Vergles, J. ., Čulo, M. I. M. I., Cutolo, M. ., Sulli, A. ., Derk Ct, C. T., Jimenez Sa, S. A., Siakka, P. ., Søndergaard, K. ., Stengaard Pedersen, K. ., Cabane, J. ., Tiev Kp, K. P., Mihai, C. ., Sfrent Cornateanu, R. ., Jendro, M. ., Tuvik, P. ., Antivalle, M. ., Randisi, G. ., Seidel, M. ., Clarenbach, R. ., Simsek, I. ., Dinc, A. ., Inanc, M. ., Capraru Ms, M. S., Capraru, D. ., Bañegil, I. ., Richter, J. ., Alhasani, S. ., Földvari, I. ., Pinto, S. ., Brandão, F. ., Ribi, Camillo, and Chizzolini, Carlo
Subjects: Male, Systemic disease, Databases, Factual, Cross-sectional study, Scleroderma, Immunopathology, Immunology and Allergy, Age of Onset, skin and connective tissue diseases, ddc:616, integumentary system, Nuclear Proteins, Orvostudományok, Middle Aged, Connective tissue disease, Extended Report, Raynaud Disease/etiology/immunology, DNA Topoisomerases, Type I, Nuclear Proteins/immunology, Female, Adult, medicine.medical_specialty, Scleroderma, Diffuse/complications/immunology, Immunology, Klinikai orvostudományok, Scleroderma, Systemic/complications/immunology, Risk Assessment, General Biochemistry, Genetics and Molecular Biology, systemic sclerosis, EULAR, risk assessment, Age Distribution, Sex Factors, Rheumatology, Scleroderma, Limited, medicine, Humans, Risk factor, Aged, Autoantibodies, Scleroderma, Systemic, business.industry, Autoantibody, Raynaud Disease, medicine.disease, Dermatology, Cross-Sectional Studies, Scleroderma, Diffuse, Scleroderma, Limited/complications/immunology, Age of onset, business, Autoantibodies/blood
Abstract: Background: Systemic sclerosis (SSc) is a multisystem autoimmune disease which is classified into a diffuse cutaneous (dcSSc) and a limited cutaneous (lcSSc) subset according to the skin involvement. In order to better understand the vascular, immunological and fibrotic processes of SSc and to guide its treatment the EULAR Scleroderma Trials And Research (EUSTAR) group was formed in June 2004. Aims and Methods: EUSTAR collects prospectively the Minimal Essential Data Set (MEDS) on all sequential patients fulfilling the ACR diagnostic criteria in participating centres. We aimed to characterize demographic, clinical and laboratory characteristics of disease presentation in SSc and analysed EUSTAR baseline visits. Results: In April 2006, a total of 3656 patients (1349 with dcSSc and 2101 with lcSSc) were enrolled in 102 centres and 30 countries. 1330 individuals had autoantibodies against Scl70 and 1106 against anticentromere antibodies. 87% of patients were female. On multivariate analysis, scleroderma subsets (dcSSc vs. lcSSc), antibody status and age at onset of Raynaud’s phenomenon, but not gender were independently associated with the prevalence of organ manifestations. Autoantibody status in this analysis appeared more closely associated with clinical manifestations than were SSc subsets. Conclusion: dcSSc and lcSSc subsets are associated with particular organ manifestations, but in this analysis the clinical distinction appeared superseded by an antibody based classification in predicting some scleroderma complications. The EUSTAR MEDS data base facilitates the analysis of clinical patterns in SSc and contributes to the standardised assessment and monitoring of SSc internationally.
Published: 2007

17. Outcomes of patients with systemic sclerosis-associated polyarthritis and myopathy treated with tocilizumab or abatacept: a EUSTAR observational study

Author: Elhai, M., Meunier, M., Matucci Cerinic, M., Maurer, B., Riemekasten, G., Leturcq, T., Pellerito, R., Von Muhlen, C. A., Vacca, A., Airo, P., Bartoli, F., Fiori, G., Bokarewa, M., Riccieri, Valeria, Becker, M., Avouac, J., Muller Ladner, U., Distler, O., Allanore, Y., Eular Scleroderma Trials, Eustar (., Research, Group, University of Zurich, and Allanore, Yannick
Subjects: Male, Immunoconjugates, systemic sclerosis, 2745 Rheumatology, Arthritis, Scleroderma, chemistry.chemical_compound, Immunology and Allergy, Prospective Studies, skin and connective tissue diseases, 10051 Rheumatology Clinic and Institute of Physical Medicine, Middle Aged, Connective tissue disease, Treatment Outcome, Antirheumatic Agents, 2723 Immunology and Allergy, Polyarthritis, Female, medicine.symptom, medicine.drug, myopathy, musculoskeletal diseases, Adult, medicine.medical_specialty, Immunology, 610 Medicine & health, Antibodies, Monoclonal, Humanized, polyarthritis, General Biochemistry, Genetics and Molecular Biology, Abatacept, tocilizumab, Tocilizumab, Rheumatology, Refractory, Muscular Diseases, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, medicine, Humans, Myopathy, 2403 Immunology, Scleroderma, Systemic, business.industry, medicine.disease, Surgery, abatacept, chemistry, business
Abstract: ObjectiveTo evaluate the safety and effectiveness of tocilizumab and abatacept in systemic sclerosis (SSc)-polyarthritis or SSc-myopathy.Methods20 patients with SSc with refractory polyarthritis and seven with refractory myopathy from the EUSTAR (EULAR Scleroderma Trials and Research) network were included: 15 patients received tocilizumab and 12 patients abatacept. All patients with SSc-myopathy received abatacept. Clinical and biological assessments were made at the start of treatment and at the last infusion.ResultsAfter 5 months, tocilizumab induced a significant improvement in the 28-joint count Disease Activity Score and its components, with 10/15 patients achieving a EULAR good response. Treatment was stopped in two patients because of inefficacy. After 11 months’ treatment of patients with abatacept, joint parameters improved significantly, with 6/11 patients fulfilling EULAR good-response criteria. Abatacept did not improve muscle outcome measures in SSc-myopathy. No significant change was seen for skin or lung fibrosis in the different groups. Both treatments were well tolerated.ConclusionsIn this observational study, tocilizumab and abatacept appeared to be safe and effective on joints, in patients with refractory SSc. No trend for any change of fibrotic lesions was seen but this may relate to the exposure time and inclusion criteria. Larger studies with longer follow-up are warranted to further determine the safety and effectiveness of these drugs in SSc.
Published: 2013

18. A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci

Author: Martin, J.E., Assassi, S., Diaz-Gallo, L.M., Broen, J.C.A., Simeon, C.P., Castellvi, I., Vicente-Rabaneda, E., Fonollosa, V., Ortego-Centeno, N., Gonzalez-Gay, M.A., Espinosa, G., Carreira, P., Scleroderma, G. Spanish, consortium, S., group, U.S.S.G., Biolupus, ., Camps, M., Sabio, J.M., D'Alfonso, S., Vonk, M.C., Voskuyl, A.E., Schuerwegh, A.J., Kreuter, A., Witte, T. de, Riemekasten, G., Hunzelmann, N., Airo, P., Beretta, L., Scorza, R., Lunardi, C., Laar, J. van, Chee, M.M., Worthington, J., Herrick, A., Denton, C., Fonseca, C., Tan, F.K., Arnett, F., Zhou, X., Reveille, J.D., Gorlova, O., Koeleman, B.P., Radstake, T.R.D.J., Vyse, T., Mayes, M.D., Alarcon-Riquelme, M.E., Martin, J., Rheumatology, and CCA - Disease profiling
Subjects: SLE, Genome-wide association study, Disease, medicine.disease_cause, Systemic scleroderma, Autoimmunity, 0302 clinical medicine, Risk Factors, Lupus Erythematosus, Systemic, skin and connective tissue diseases, Genetics (clinical), Genetics, 0303 health sciences, education.field_of_study, Association Studies Articles, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, General Medicine, Neoplasm Proteins, 3. Good health, DNA-Binding Proteins, SYSTEMIC SCLEROSIS, Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2], Co-Repressor Proteins, Population, Nerve Tissue Proteins, Receptors, Cell Surface, Single-nucleotide polymorphism, Protein Serine-Threonine Kinases, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Genetic predisposition, medicine, Humans, Genetic Predisposition to Disease, genome-wide association studies, education, Molecular Biology, 030304 developmental biology, Genetic association, 030203 arthritis & rheumatology, Scleroderma, Systemic, Genetic Variation, Reproducibility of Results, medicine.disease, Genetic Loci, Case-Control Studies, Immunology, Genome-Wide Association Study
Abstract: Item does not contain fulltext Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21 109 (6835 cases and 14 274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 x 10(-11), OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 x 10(-11), OR = 1.20) and JAZF1 (P = 1.11 x 10(-8), OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.
Published: 2013

19. The autoimmune disease-associated IL2RA locus is involved in the clinical manifestations of systemic sclerosis

Author: Martin, J.E., Carmona, F.D., Broen, J.C.A., Simeon, C.P., Vonk, M.C., Carreira, P., Rios-Fernandez, R., Espinosa, G., Vicente-Rabaneda, E., Tolosa, C., Garcia-Hernandez, F.J., Castellvi, I., Fonollosa, V., Gonzalez-Gay, M.A., Saez-Comet, L., Portales, R.G., Pena, P.G. de la, Fernandez-Castro, M., Diaz, B., Martinez-Estupinan, L., Coenen, M., Voskuyl, A.E., Schuerwegh, A.J., Vanthuyne, M., Houssiau, F., Smith, V., Keyser, F. de, Langhe, E. de, Riemekasten, G., Witte, T., Hunzelmann, N., Kreuter, A., Palm, O., Chee, M.M., Laar, J.M. van, Denton, C., Herrick, A., Worthington, J., Koeleman, B.P.C., Radstake, T.R.D.J., Fonseca, C., Martin, J., Spanish Scleroderma Grp, Rheumatology, and CCA - Innovative therapy
Subjects: Adult, Interleukin 2, systemic sclerosis, Immunology, PATHOGENESIS, BETA, Genome-wide association study, Locus (genetics), Biology, Polymorphism, Single Nucleotide, anti-centromere auto-antibody, CLASSIFICATION, Autoimmune Diseases, Immune tolerance, Pathogenesis, INTERLEUKIN-2-RECEPTOR, SCLERODERMA, rs12722495, Genetics, medicine, Medicine and Health Sciences, Humans, REGULATORY T-CELLS, Allele, GENOME-WIDE ASSOCIATION, skin and connective tissue diseases, Genomic disorders and inherited multi-system disorders Molecular epidemiology [IGMD 3], Genetics (clinical), Autoimmune disease, Scleroderma, Systemic, IL2RA, rs2104286, Interleukin-2 Receptor alpha Subunit, Odds ratio, Middle Aged, medicine.disease, Infection and autoimmunity Auto-immunity, transplantation and immunotherapy [NCMLS 1], Genetic Loci, rs11594656, Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2], medicine.drug
Abstract: Contains fulltext : 109760.pdf (Publisher’s version ) (Closed access) Regulatory T cells (T(regs)) are crucial in the maintenance of the immune tolerance and seem to have an important role in systemic sclerosis (SSc). The interleukin 2 receptor alpha (IL2RA) is an important T(reg) marker, and polymorphisms of IL2RA gene are associated with a number of autoimmune diseases. Therefore, we aimed to investigate for the first time the association of the IL2RA locus in SSc. For this purpose, a total of 3023 SSc patients and 2735 matched healthy controls, from six European Caucasian cohorts, were genotyped for the IL2RA gene variants rs11594656, rs2104286 and rs12722495 using the TaqMan allelic discrimination technology. The overall meta-analysis reached statistical significance when the three polymorphisms were tested for association with SSc, the limited subtype (lcSSc) and anti-centromere auto-antibodies (ACAs). However, no significant P-values were obtained when the ACA-positive patients were removed from the SSc and lcSSc groups, suggesting that these associations rely on ACA positivity. The strongest association signal with ACA production was detected for rs2104286 (P(FDR)=2.07 x 10(-4), odds ratio=1.30 (1.14-1.47)). The associations of rs11594656 and rs12722495 were lost after conditioning to rs2104286, and allelic combination tests did not evidence a combined effect, indicating that rs2104286 best described the association between IL2RA and ACA presence in SSc. 01 februari 2012
Published: 2012

20. Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis

Author: Cenit, M.C., Simeon, C.P., Vonk, M.C., Callejas-Rubio, J.L., Espinosa, G., Carreira, P., Blanco, F.J., Narvaez, J., Tolosa, C., Roman-Ivorra, J.A., Gomez-Garcia, I., Garcia-Hernandez, F.J., Gallego, M., Garcia-Portales, R., Egurbide, M.V., Fonollosa, V., Garcia de la Pena, P., Lopez-Longo, F.J., Gonzalez-Gay, M.A., The Spanish Scleroderma, G., Hesselstrand, R., Riemekasten, G., Witte, T.J.M. de, Voskuyl, A.E., Schuerwegh, A.J., Madhok, R., Fonseca, C., Denton, C., Nordin, A., Palm, O., Laar, J.M. van, Hunzelmann, N., Distler, J.H., Kreuter, A., Herrick, A., Worthington, J., Koeleman, B.P., Radstake, T.R.D.J., Martin, J., Rheumatology, and CCA - Innovative therapy
Subjects: Male, Immunology, Disease, Polymorphism, Single Nucleotide, White People, symbols.namesake, Rheumatology, medicine, Humans, Immunology and Allergy, SNP, Genetic Predisposition to Disease, Allele, Interleukin 6, skin and connective tissue diseases, Autoimmune disease, Scleroderma, Systemic, biology, Interleukin-6, business.industry, medicine.disease, Infection and autoimmunity Auto-immunity, transplantation and immunotherapy [NCMLS 1], Europe, Minor allele frequency, Bonferroni correction, Meta-analysis, Disease Progression, symbols, biology.protein, Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2], Female, business
Abstract: Objective.Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and phenotype expression of SSc.Methods.We performed a large metaanalysis including a total of 2749 cases and 3189 controls from 6 white populations (Germany, The Netherlands, Norway, Spain, Sweden, and United Kingdom). Three IL6 single-nucleotide polymorphisms (SNP; rs2069827, rs1800795, and rs2069840) were selected by SNP tagging and genotyped using TaqMan® allele discrimination technology.Results.Individual SNP metaanalysis showed no evidence of association of the 3 IL6 genetic variants with the global disease. Phenotype analyses revealed a significant association between the minor allele of rs2069840 and the limited cutaneous SSc clinical form (Bonferroni p = 0.036, OR 1.14, 95% CI 1.04–1.25). A trend of association between the minor allele of the rs1800795 and the diffuse cutaneous SSc clinical form was also evident (Bonferroni p = 0.072, OR 0.86, 95% CI 0.77–0.96). In the IL6 allelic combination analyses, the GGC allelic combination rs2069827-rs1800795-rs2069840 showed an association with overall SSc (Bonferroni p = 0.016, OR 1.13, 95% CI 1.04–1.23).Conclusion.Our results suggest that the IL6 gene may influence the development of SSc and its progression.
Published: 2012

21. Polymorphisms in the interleukin 4, interleukin 13, and corresponding receptor genes are not associated with systemic sclerosis and do not influence gene expression

Author: Broen, J.C., Dieude, P., Vonk, M.C., Beretta, L., Carmona, F.D., Herrick, A., Worthington, J., Hunzelmann, N., Riemekasten, G., Kiener, H., Scorza, R., Simeon, C.P., Fonollosa, V., Spanish Systemic Sclerosis, G., Carreira, P., Ortego-Centeno, N., Gonzalez-Gay, M.A., Airo, P., Coenen, M.J., Tsang, K., Aliprantis, A.O., Martin, J., Allanore, Y., and Radstake, T.R.
Subjects: Adult, Myeloid, Genotype, Immunology, Gene Expression, Single-nucleotide polymorphism, Rheumatology, Gene expression, Immunology and Allergy, Medicine, SNP, Humans, Genetic Predisposition to Disease, Receptor, skin and connective tissue diseases, Genomic disorders and inherited multi-system disorders Molecular epidemiology [IGMD 3], Interleukin 4, Aged, Interleukin-13, Polymorphism, Genetic, Scleroderma, Systemic, business.industry, Receptors, Interleukin-13, Interleukin-4 Receptor alpha Subunit, Middle Aged, Infection and autoimmunity Auto-immunity, transplantation and immunotherapy [NCMLS 1], Europe, medicine.anatomical_structure, Interleukin 13, Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2], Female, Interleukin-4, business
Abstract: Objective.Polymorphisms in the genes encoding interleukin 4 (IL4), interleukin 13 (IL13), and their corresponding receptors have been associated with multiple immune-mediated diseases. Our aim was to validate these previous observations in patients with systemic sclerosis (SSc) and scrutinize the effect of the polymorphisms on gene expression in various populations of peripheral blood leukocytes.Methods.We genotyped a cohort of 2488 patients with SSc and 2246 healthy controls from The Netherlands, Spain, United Kingdom, Italy, Germany, and France. Taqman assays were used to genotype single-nucleotide polymorphisms (SNP) in the following genes: (1) IL4 (−590C>T/rs2243250); (2) IL4 receptor alpha (IL4RA) (Q576R/rs1801275); (3) IL13 (R130Q/rs20541 and −1112C>T/rs1800925); and (4) IL13RA1 (43163G>A/rs6646259). The effect of these polymorphisms on expression of the corresponding genes was assessed using quantitative RT-PCR on RNA derived from peripheral blood B cells, T cells, plasmacytoid dendritic cells, monocytes, and myeloid dendritic cells. We investigated whether these polymorphisms influenced development of pulmonary complications over 15 years in patients with SSc.Results.None of the investigated polymorphisms was associated with SSc or any SSc clinical subtype. We did not observe any effect on transcript levels in the cell subtypes or on development of pulmonary complications.Conclusion.Our data showed that polymorphisms in IL4, IL13, and their receptors do not play a role in SSc and do not influence the expression of their corresponding transcript in peripheral blood cells.
Published: 2012

22. Immunology and the diagnosis of lupus nephritis.

Author: Enghard, P. and Riemekasten, G.
Subjects: *LUPUS nephritis, *SYSTEMIC lupus erythematosus, *DIAGNOSIS, *IMMUNOLOGY, *URINE, *MEDICAL research, *CLINICAL medicine
Abstract: The article reports on the immunology and diagnosis of lupus nephritis (LN). It states that traditionally, serum levels of anti-dsDNA antibodies and hypocomplementemia are used to identify patients with high disease activity and at risk for developing LN. It says that biomarkers reflecting systemic lupus erythematosus (SLE) disease activity and providing specificity for renal lupus are likely to be found in the urine.
Published: 2009
Full Text: View/download PDF

23. Confirmation of association of the macrophage migration inhibitory factor gene with systemic sclerosis in a large European population

Author: Bossini-Castillo, L., Simeon, C. P., Beretta, L., Vonk, M. C., Callejas-Rubio, J. L., Espinosa, G., Carreira, P., Camps, M. T., Rodríguez-Rodríguez, L., Rodríguez-Carballeira, M., García-Hernández, F. J., López-Longo, F. J., Hernández-Hernández, V., Sáez-Comet, L., Egurbide, M. V., Hesselstrand, R., Nordin, A., Hoffmann-Vold, A. M., Vanthuyne, M., Smith, V., Langhe, E., Kreuter, A., Riemekasten, G., Witte, T., Hunzelmann, N., Voskuyl, A. E., Schuerwegh, A. J., Lunardi, C., Airó, P., Scorza, R., Shiels, P., Laar, J. M., Fonseca, C., Denton, C., Herrick, A., Jane Worthington, Koeleman, B. P., Rueda, B., Radstake, T. R., Martin, J., Spanish Scleroderma Group, Rheumatology, and CCA - Innovative therapy
Subjects: Genetic Markers, Genotype, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Scleroderma, Rheumatology, Polymorphism (computer science), Odds Ratio, MIF gene, systemic sclerosis, Medicine, SNP, Humans, Pharmacology (medical), Genetic Predisposition to Disease, Allele, skin and connective tissue diseases, Macrophage Migration-Inhibitory Factors, Macrophage migration inhibitory factor, Scleroderma, Systemic, integumentary system, business.industry, Case-control study, Translational research Immune Regulation [ONCOL 3], Infection and autoimmunity Auto-immunity, transplantation and immunotherapy [NCMLS 1], Genetic marker, Case-Control Studies, Immunology, Systemic sclerosis, Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2], business, Polymorphisms
Abstract: The aim of this study was to confirm the implication of macrophage migration inhibitory factor (MIF) gene in SSc susceptibility or clinical phenotypes in a large European population.

24. Clinical determinants of elevated systolic pulmonary artery pressure measured by transthoracic Doppler echocardiography in early systemic sclerosis

Author: Patricia E Carreira, Carmona, L., Joven, B. E., Loza, E., Andreu, J. L., Riemekasten, G., Vettori, S., Allanore, Y., Balbir-Gurman, A., Airò, P., Walker, U. A., Damjanov, N., Ananieva, L. P., Rednic, S., Czirják, L., Distler, O., Farge, D., Hesselstrand, R., Corrado, A., Caramaschi, P., Tikly, M., Matucci-Cerinic, M., Carreira, Patricia E., Carmona, Loreto, Joven, Beatriz E., Loza, Estibaliz, Andreu, Josã© Lui, Riemekasten, Gabriela, Vettori, Serena, Allanore, Yannick, Balbir gurman, Alexandra, Airã², Paolo, Walker, Ulrich A., Damjanov, Nemanja, Ananieva, Lidia P., Rednic, Simona, Czirjã¡k, Lã¡szlã³, Distler, Oliver, Farge, Dominique, Hesselstrand, Roger, Corrado, Ada, Caramaschi, Paola, Tikly, Mohammed, and Matucci cerinic, Marco
Subjects: Adult, Male, Scleroderma, Systemic, Systole, Immunology, Middle Aged, Pulmonary Artery, Pulmonary arterial hypertension, Echocardiography, Doppler, Systemic sclerosi, Cross-Sectional Studies, Logistic Models, Rheumatology, Right heart catheterisation, Echocardiography, Immunology and Allergy, Humans, Female, Aged
Abstract: Objective. To explore the prevalence and clinical associations of elevated systolic pulmonary artery pressure (sPAP), measured by Transthoracic Dopplerechocardiography (TTE) in patients with early systemic sclerosis (SSc). Methods. A cross-sectional analysis of the prospective EULAR Scleroderma Trial and Research (EUSTAR) database was performed. SSc patients with < 3 years from the first non-Raynaud's phenomenon (RP) symptom at baseline EUSTAR visit, were selected. Elevated sPAP was defined as sPAP > 40 mmHg on baseline TTE. First visit SSc related variables, including disease subsets, antibodies and visceral involvement, were examined. Results. From 1,188 patients, 81% were women. Mean (SD) age at first non-RP symptom was 50 (14) years, 55% had limited cutaneous SSc (lcSSc) and 42% active disease. Elevated sPAP was found in 17% of patients, both lcSSc and diffuse cutaneous SSc (dc- SSc). In lcSSc, older age at first non- RP symptom, ACA positivity, joint contractures, restrictive defect and lower DLCO, were independently associated with elevated sPAP. In dcSSc, older age at first non-RP symptom, longer time between RP onset and first non-RP symptom, digital ulcers, cardiac blocks, and proteinuria were associated with elevated sPAP. Conclusion. The prevalence of elevated sPAP on TTE in early SSc patients is considerable. Association with cardiac, lung and renal involvement suggests that, although some patients might have pulmonary arterial hypertension, others may present pulmonary hypertension secondary to lung or heart involvement. Our findings emphasise the need to consider right heart catheterisation in selected early SSc patients with PH suspicion, to clearly determine the cause of PH.

25. Stratification in systemic sclerosis according to autoantibody status versus skin involvement: a study of the prospective EUSTAR cohort

Author: Muriel Elhai, Nanthara Sritharan, Marouane Boubaya, Alexandra Balbir-Gurman, Elise Siegert, Eric Hachulla, Jeska de Vries-Bouwstra, Gabriela Riemekasten, Jörg H W Distler, Edoardo Rosato, Francesco Del Galdo, Fabian A Mendoza, Daniel E Furst, Carlos de la Puente, Anna-Maria Hoffmann-Vold, Armando Gabrielli, Oliver Distler, Coralie Bloch-Queyrat, Yannick Allanore, Marco Matucci Cerinic, Ulrich Walker, Florenzo Iannone, Suzana Jordan, Radim Becvar, Otylia Kowal Bielecka, Maurizio Cutolo, Giovanna Cuomo, Claudia Kedor, Simona Rednic, Jérome Avouac, P. Vlachoyiannopoulos, C. Montecucco, Jiri Stork, Murat Inanc, Patricia E. Carreira, Srdan Novak, László Czirják, Michele Iudici, Eugene J. Kucharz, Elisabetta Zanatta, Katja Perdan-Pirkmajer, Bernard Coleiro, Gianluca Moroncini, Dominique Farge Bancel, Paolo Airò, Roger Hesselstrand, Mislav Radic, Yolanda Braun-Moscovici, Andrea Lo Monaco, Nicolas Hunzelmann, Raffaele Pellerito, Alessandro Giollo, Jadranka Morovic-Vergles, Christopher Denton, Madelon Vonk, Nemanja Damjanov, Jörg Henes, Vera Ortiz Santamaria, Stefan Heitmann, Dorota Krasowska, Paul Hasler, Michaela Kohm, Ivan Foeldvari, Gianluigi Bajocchi, Maria João Salvador, Bojana Stamenkovic, Carlo Francesco Selmi, Mohammed Tikly, Lidia P. Ananieva, Ariane Herrick, Ulf Müller-Ladner, Raffaele De Palma, Merete Engelhart, Gabriela Szücs, Cristina Sobrino Grande, Øyvind Midtvedt, David Launay, Valeria Riccieri, Ruxandra Maria Ionescu, Ami Sha, Ana Maria Gheorghiu, Cord Sunderkötter, Francesca Ingegnoli, Luc Mouthon, Vanessa Smith, Francesco Paolo Cantatore, Susanne Ullman, Carlos Alberto von Mühlen, Maria Rosa Pozzi, Kilian Eyerich, Piotr Wiland, Marie Vanthuyne, Juan Jose Alegre-Sancho, Kristine Herrmann, Ellen De Langhe, Branimir Anic, Maria Üprus, Sule Yavuz, Brigitte Granel, Carolina de Souza Müller, Joanna Busquets, Svetlana Agachi, Simon Stebbings, D'Alessandro Mathieu, Percival D. Sampaio-Barros, Lisa Stamp, Kamal Solanki, Douglas Veale, Esthela Loyo, Mengtao Li, Walid Ahmed Abdel Atty Mohamed, Antonietta Gigante, Fahrettin Oksel, Cristina-Mihaela Tanaseanu, Rosario Foti, Codrina Ancuta, Britta Maurer, Jacob van Laar, Cristiane Kayser, Nihal Fathi, Paloma García de la Peña Lefebvre, Jean Sibilia, Ira Litinsky, Giuseppina Abignano, Goda Seskute, Lesley Ann Saketkoo, Eduardo Kerzberg, Washington Bianchi, Ivan Castellví, Massimiliano Limonta, Doron Rimar, Maura Couto, François Spertini, Antonella Marcoccia, Sarah Kahl, Ivien M. Hsu, Thierry Martin, Sergey Moiseev, Lorinda S. Chung, Tim Schmeiser, Dominik Majewski, Zbigniew Zdrojewski, Julia Martínez-Barrio, Vera Bernardino, Sabine Sommerlatte, Yair Levy, Elena Rezus, Omer Nuri Pamuk, Piercarlo Sarzi Puttini, Hadi Poormoghim, Ina Kötter, Francis Gaches, Laura Belloli, Petros Sfikakis, Juliana Markus, Gary R Feldman, Ana-Maria Ramazan, H.U. Scherer, Marie-Elise Truchetet, Alain Lescoat, Lorenzo Dagna, J.M. van Laar, Lidia Rudnicka, Susana Oliveira, Fabiola Atzeni, Masataka Kuwana, Arsene Mekinian, Mickaël Martin, Yoshiya Tanaka, Elhai, M., Sritharan, N., Boubaya, M., Balbir-Gurman, A., Siegert, E., Hachulla, E., de Vries-Bouwstra, J., Riemekasten, G., Distler, J. H. W., Rosato, E., Del Galdo, F., Mendoza, F. A., Furst, D. E., de la Puente, C., Hoffmann-Vold, A. -M., Gabrielli, A., Distler, O., Bloch-Queyrat, C., Allanore, Y., Matucci Cerinic, M., Walker, U., Iannone, F., Jordan, S., Becvar, R., Kowal Bielecka, O., Cutolo, M., Cuomo, G., Kedor, C., Rednic, S., Avouac, J., Vlachoyiannopoulos, P., Montecucco, C., Stork, J., Inanc, M., Carreira, P. E., Novak, S., Czirjak, L., Iudici, M., Kucharz, E. J., Zanatta, E., Perdan-Pirkmajer, K., Coleiro, B., Moroncini, G., Farge Bancel, D., Airo, P., Hesselstrand, R., Radic, M., Braun-Moscovici, Y., Lo Monaco, A., Hunzelmann, N., Pellerito, R., Giollo, A., Morovic-Vergles, J., Denton, C., Vonk, M., Damjanov, N., Henes, J., Ortiz Santamaria, V., Heitmann, S., Krasowska, D., Hasler, P., Kohm, M., Foeldvari, I., Bajocchi, G., Salvador, M. J., Stamenkovic, B., Selmi, C. F., Tikly, M., Ananieva, L. P., Herrick, A., Muller-Ladner, U., De Palma, R., Engelhart, M., Szucs, G., Sobrino Grande, C., Midtvedt, O., Launay, D., Riccieri, V., Ionescu, R. M., Sha, A., Gheorghiu, A. M., Sunderkotter, C., Ingegnoli, F., Mouthon, L., Smith, V., Cantatore, F. P., Ullman, S., Alberto von Muhlen, C., Pozzi, M. R., Eyerich, K., Wiland, P., Vanthuyne, M., Alegre-Sancho, J. J., Herrmann, K., De Langhe, E., Anic, B., Uprus, M., Yavuz, S., Granel, B., de Souza Muller, C., Busquets, J., Agachi, S., Stebbings, S., Mathieu, D. A., Sampaio-Barros, P. D., Stamp, L., Solanki, K., Veale, D., Loyo, E., Li, M., Abdel Atty Mohamed, W. A., Gigante, A., Oksel, F., Tanaseanu, C. -M., Foti, R., Ancuta, C., Maurer, B., van Laar, J., Kayser, C., Fathi, N., Garcia de la Pena Lefebvre, P., Sibilia, J., Litinsky, I., Abignano, G., Seskute, G., Saketkoo, L. A., Kerzberg, E., Bianchi, W., Castellvi, I., Limonta, M., Rimar, D., Couto, M., Spertini, F., Marcoccia, A., Kahl, S., Hsu, I. M., Martin, T., Moiseev, S., Chung, L. S., Schmeiser, T., Majewski, D., Zdrojewski, Z., Martinez-Barrio, J., Bernardino, V., Sommerlatte, S., Levy, Y., Rezus, E., Nuri Pamuk, O., Sarzi Puttini, P., Poormoghim, H., Kotter, I., Gaches, F., Belloli, L., Sfikakis, P., Markus, J., Feldman, G. R., Ramazan, A. -M., Scherer, H. U., Truchetet, M. -E., Lescoat, A., Dagna, L., van Laar, J. M., Rudnicka, L., Oliveira, S., Atzeni, F., Kuwana, M., Mekinian, A., Martin, M., and Tanaka, Y.
Subjects: Rheumatology, Immunology, Immunology and Allergy
Abstract: Background: The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis. Methods: For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed. Findings: We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15·4%) of 10 709 were male, 9062 (84·6%) were female, mean age was 54·4 (SD 13·8) years, and mean disease duration was 7·9 (SD 8·2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0·82, 95% CI 0·81–0·84 for cutaneous only vs 0·84, 0·82–0·85 for antibody only vs 0·84, 0·83–0·86 for combined) or for progression-free survival (0·70, 0·69–0·71 vs 0·71, 0·70–0·72 vs 0·71, 0·70–0·72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0·57, 0·46–0·71 for antibody only vs 0·29, 0·19–0·39 for cutaneous only) and disease progression (0·36, 0·29–0·46 vs 0·21, 0·14–0·28). The antibody-only model did better than the cutaneous-only model in predicting renal crisis (AUC 0·72, 0·70–0·74 for antibody only vs 0·66, 0·64–0·69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0·76, 0·75–0·77 vs 0·71, 0·70–0·72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement. Interpretation: The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management. Funding: World Scleroderma Foundation.
Published: 2022

26. Vasodilators and low-dose acetylsalicylic acid are associated with a lower incidence of distinct primary myocardial disease manifestations in systemic sclerosis: results of the DeSScipher inception cohort study

Author: László Czirják, Brigitte Krummel-Lorenz, Carina Mihai, Serena Fasano, Giuseppina Abignano, Serena Guiducci, Gabriele Valentini, Rosaria Irace, Armando Gabrielli, Francesco Del Galdo, Britta Maurer, Ivan Foeldvari, Ulrich A. Walker, Svetlana I. Nihtyanova, Alessandra Vacca, Dörte Huscher, Ulf Mueller-Ladner, Marc Frerix, Jérôme Avouac, Veronika K. Jaeger, Christopher P. Denton, Oliver Distler, Marco Matucci-Cerinic, Ingo H. Tarner, T. Schmeiser, L. Ananieva, Simona Rednic, Sergey Moiseev, Ana Maria Gherghe, Yannick Allanore, Antonella Riccardi, Elise Siegert, Joerg Henes, Gabriela Riemekasten, Veronika Lóránd, Valentina Messiniti, Valentini, G., Huscher, D., Riccardi, A., Fasano, S., Irace, R., Messiniti, V., Matucci-Cerinic, M., Guiducci, S., Distler, O., Maurer, B., Avouac, J., Tarner, I. H., Frerix, M., Riemekasten, G., Siegert, E., Czirjak, L., Lorand, V., Denton, C. P., Nihtyanova, S., Walker, U. A., Jaeger, V. K., Del Galdo, F., Abignano, G., Ananieva, L. P., Gherghe, A. M., Mihai, C., Henes, J. C., Schmeiser, T., Vacca, A., Moiseev, S., Foeldvari, I., Gabrielli, A., Krummel-Lorenz, B., Rednic, S., Allanore, Y., and Mueller-Ladner, U.
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, preventative role of vasodilator therapy, Vasodilator Agents, Immunology, primary myocardial disease in scleroderma, Vasodilation, General Biochemistry, Genetics and Molecular Biology, Ventricular Function, Left, 03 medical and health sciences, Ventricular Dysfunction, Left, 0302 clinical medicine, Rheumatology, Fibrosis, Internal medicine, medicine, Immunology and Allergy, Humans, Survival analysis, Proportional Hazards Models, 030203 arthritis & rheumatology, Heart Failure, Ejection fraction, Scleroderma, Systemic, Aspirin, Proportional hazards model, business.industry, Incidence (epidemiology), Incidence, Arrhythmias, Cardiac, Middle Aged, medicine.disease, 030104 developmental biology, Heart failure, cardiovascular system, Cardiology, Female, Endothelin receptor, business, Cardiomyopathies
Abstract: ObjectivesTo investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) Methods601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5–4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed.ResultsDuring 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF ConclusionsThe present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA.
Published: 2019

27. Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the european scleroderma trials and research (eustar) cohort

Author: Wu, Wanlong, Jordan, Suzana, Graf, Nicole, Pena, Janethe de Oliveira, Curram, John, Allanore, Yannick, Matucci-Cerinic, Marco, Pope, Janet E., Denton, Christopher P., Khanna, Dinesh, Distler, Oliver, Guiducci, Serena, Walker, Ulrich, Jaeger, Veronika, Bannert, Bettina, Lapadula, Giovanni, Becvarare, Radim, Cutolo, Maurizio, Valentini, Gabriele, Siegert, Elise, Rednic, Simona, Montecucco, C., Carreira, Patricia E., Novak, Srdan, Czirjak, Laszlo, Varju, Cecilia, Chizzolini, Carlo, Allai, Daniela, Kucharz, Eugene J., Cozzi, Franco, Rozman, Blaz, Mallia, Carmel, Gabrielli, Armando, Bancel, Dominique Farge, Airo, Paolo, Hesselstrand, Roger, Martinovic, Duska, Balbir-Gurman, Alexandra, Braun-Moscovici, Yolanda, Hunzelmann, Nicolas, Pellerito, Raffaele, Caramaschi, Paola, Black, Carol, Damjanov, Nemanja, Henes, Joerg, Ortiz Santamaria, Vera, Heitmann, Stefan, Seidel, Matthias, Pereira Da Silva, Jose Antonio, Stamenkovic, Bojana, Selmi, Carlo Francesco, Tikly, Mohammed, Denisov, Lev N., Mueller-Ladner, Ulf, Engelhart, Merete, Hachulla, Eric, Riccieri, Valeria, Ionescu, Ruxandra Maria, Mihai, Carina, Sunderkoetter, Cord, Kuhn, Annegret, Schett, Georg, Distler, Joerg, Meroni, Pierluigi, Ingegnoli, Francesca, Mouthon, Luc, De Keyser, Filip, Smith, Vanessa, Cantatore, Francesco Paolo, Corrado, Ada, Ullman, Susanne, Iversen, Line, Pozzi, Maria Rosa, Eyerich, Kilian, Hein, Ruediger, Knott, Elisabeth, Wiland, Piotr, Szmyrka-Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Madej, Marta, Jose Alegre-Sancho, Juan, Krummel-Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Guenther, Claudia, Anne, Erler, Westhovens, Rene, De Langhe, Ellen, Lenaerts, Jan, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Uprus, Maria, Otsa, Kati, Yavuz, Sule, Radominski, Sebastiao Cezar, Mueller, Carolina de Souza, Azevedo, Valderilio Feijo, Popa, Sergei, Zenone, Thierry, Stebbings, Simon, Highton, John, Mathieu, Alessandro, Vacca, Alessandra, Stamp, Lisa, Chapman, Peter, O'Donnell, John, Solanki, Kamal, Doube, Alan, Veale, Douglas, O'Rourke, Marie, Loyo, Esthela, Li, Mengtao, Rosato, Edoardo, Amoroso, Antonio, Gigante, Antonietta, Oksel, Fahrettin, Yargucu, Figen, Tanaseanu, Cristina-Mihaela, Popescu, Monica, Dumitrascu, Alina, Tiglea, Isabela, Foti, Rosario, Visalli, Elisa, Benenati, Alessia, Amato, Giorgio, Ancuta, Codrina, Chirieac, Rodica, Villiger, Peter, Adler, Sabine, Dan, Diana, de la Pena Lefebvre, Paloma Garcia, Rodriguez Rubio, Silvia, Valero Exposito, Marta, Sibilia, Jean, Chatelus, Emmanuel, Gottenberg, Jacques Eric, Chifflot, Helene, Litinsky, Ira, Del Galdo, Francesco, Venalis, Algirdas, Saketkoo, Lesley Ann, Lasky, Joseph A., Kerzberg, Eduardo, Montoya, Fabiana, Cosentino, Vanesa, Limonta, Massimiliano, Brucato, Antonio Luca, Lupi, Elide, Spertini, Francois, Ribi, Camillo, Buss, Guillaume, Martin, Thierry, Guffroy, Aurelien, Poindron, Vincent, Chung, Lori, Schmeiser, Tim, Zebryk, Pawel, Riso, Nuno, Riemekasten, Gabriela, Rezus, Elena, Puttini, Piercarlo Sarzi, Wu, W., Jordan, S., Graf, N., de Oliveira Pena, J., Curram, J., Allanore, Y., Matucci-Cerinic, M., Pope, J. E., Denton, C. P., Khanna, D., Distler, O., Guiducci, S., Walker, U., Jaeger, V., Bannert, B., Lapadula, G., Becvarare, R., Cutolo, M., Valentini, G., Siegert, E., Rednic, S., Montecucco, C., Carreira, P. E., Novak, S., Czirjak, L., Varju, C., Chizzolini, C., Allai, D., Kucharz, E. J., Cozzi, F., Rozman, B., Mallia, C., Gabrielli, A., Bancel, D. F., Airo, P., Hesselstrand, R., Martinovic, D., Balbir-Gurman, A., Braun-Moscovici, Y., Hunzelmann, N., Pellerito, R., Caramaschi, P., Black, C., Damjanov, N., Henes, J., Santamaria, V. O., Heitmann, S., Seidel, M., Pereira Da Silva, J. A., Stamenkovic, B., Selmi, C. F., Tikly, M., Denisov, L. N., Muller-Ladner, U., Engelhart, M., Hachulla, E., Riccieri, V., Ionescu, R. M., Mihai, C., Sunderkotter, C., Kuhn, A., Schett, G., Distler, J., Meroni, P., Ingegnoli, F., Mouthon, L., De Keyser, F., Smith, V., Cantatore, F. P., Corrado, A., Ullman, S., Iversen, L., Pozzi, M. R., Eyerich, K., Hein, R., Knott, E., Wiland, P., Szmyrka-Kaczmarek, M., Sokolik, R., Morgiel, E., Madej, M., Alegre-Sancho, J. J., Krummel-Lorenz, B., Saar, P., Aringer, M., Gunther, C., Anne, E., Westhovens, R., De Langhe, E., Lenaerts, J., Anic, B., Baresic, M., Mayer, M., Uprus, M., Otsa, K., Yavuz, S., Radominski, S. C., de Souza Muller, C., Azevedo, V. F., Popa, S., Zenone, T., Stebbings, S., Highton, J., Mathieu, A., Vacca, A., Stamp, L., Chapman, P., O'Donnell, J., Solanki, K., Doube, A., Veale, D., O'Rourke, M., Loyo, E., Li, M., Rosato, E., Amoroso, A., Gigante, A., Oksel, F., Yargucu, F., Tanaseanu, C. -M., Popescu, M., Dumitrascu, A., Tiglea, I., Foti, R., Visalli, E., Benenati, A., Amato, G., Ancuta, C., Chirieac, R., Villiger, P., Adler, S., Dan, D., de la Pena Lefebvre, P. G., Rubio, S. R., Exposito, M. V., Sibilia, J., Chatelus, E., Gottenberg, J. E., Chifflot, H., Litinsky, I., Del Galdo, F., Venalis, A., Saketkoo, L. A., Lasky, J. A., Kerzberg, E., Montoya, F., Cosentino, V., Limonta, M., Brucato, A. L., Lupi, E., Spertini, F., Ribi, C., Buss, G., Martin, T., Guffroy, A., Poindron, V., Chung, L., Schmeiser, T., Zebryk, P., Riso, N., Riemekasten, G., Rezus, E., Sarzi Puttini, P., Ege Üniversitesi, Chizzolini, Carlo, Allali, Danièle, University of Zurich, and Distler, Oliver
Subjects: INVOLVEMENT, Male, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, diffuse, Time Factors, Databases, Factual, Skin Diseases/etiology/mortality/physiopathology, PREDICTION, Fibrosi, 2745 Rheumatology, Diffuse/complications/mortality/pathology, Immunology, General Biochemistry, Genetics and Molecular Biology, Immunology and Allergy, Rheumatology, Kaplan-Meier Estimate, ddc:616.07, Severity of Illness Index, Scleroderma, Cohort Studies, PROGNOSTIC-FACTORS, Fibrosis, Medicine and Health Sciences, scleroderma, Lung, Skin, integumentary system, progressive skin fibrosis, Lung function decline, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, 10051 Rheumatology Clinic and Institute of Physical Medicine, DEATH, Middle Aged, ddc, Europe, VARIABILITY, factual, Cohort, Visceral organ progression, 2723 Immunology and Allergy, Disease Progression, Female, Survival Analysi, Life Sciences & Biomedicine, Cohort study, Human, Adult, Skin/pathology, medicine.medical_specialty, databases, All-cause death, risk analysis, diffuse cutaneous systemic sclerosis, 610 Medicine & health, IMPROVEMENT, Systemic Sclerosis, Skin Diseases, THICKNESS SCORE, VALIDATION, Databases, FEV1/FVC ratio, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, medicine, Humans, Factual, Survival analysis, 2403 Immunology, Science & Technology, Proportional hazards model, business.industry, Surrogate endpoint, MORTALITY, Skin Disease, fibrosis, Progressive skin fibrosi, Lung/physiopathology, biomarkers, Diffuse cutaneous systemic sclerosi, medicine.disease, Survival Analysis, all-cause death, lung function decline, visceral organ progression, adult, cohort studies, databases, factual, disease progression, female, humans, Scleroderma, Diffuse, Cohort Studie, business
Abstract: PubMed: 30852552, Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ?7, valid mRSS at 12±3 months after baseline and ?1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ?25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ?10% (53.6% vs 34.4%; p, Bayer Bayer, 1Department of Rheumatology, University Hospital Zurich, Zurich, switzerland 2Graf Biostatistics, Winterthur, switzerland 3Clinical Development Pulmonology, Bayer Us llC, Whippany, new Jersey, Usa 4Data science and analytics, Bayer plc, Reading, UK 5Rheumatology a Department, Paris Descartes University, inseRM U1016, sorbonne, Paris Cité, Cochin Hospital, Paris, France 6Division of Rheumatology, University of Florence, Florence, italy 7Department of Medicine, Division of Rheumatology, University of Western Ontario, st. Joseph’s Health Care, london, Western Ontario, Canada 8Department of Rheumatology, Royal Free Hospital, University College london, london, UK 9scleroderma Program, Department of internal Medicine, Division of Rheumatology, University of Michigan, ann arbor, Michigan, Usa Acknowledgements The authors thank nicole schneider for excellent administration and data entry into the eUsTaR cohort. Medical writing assistance was provided by adelphi Communications ltd (Bollington, UK), funded by Bayer aG (Berlin, Germany)., This study was supported by a grant from Bayer aG.
Published: 2019

28. Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: A European Scleroderma Trials and Research (EUSTAR) analysis

Author: Becker, Mike, Graf, Nicole, Sauter, Rafael, Allanore, Yannick, Curram, John, Denton, Christopher P., Khanna, Dinesh, Matucci-Cerinic, Marco, Pena, Janethe de Oliveira, Pope, Janet E., Distler, Oliver, Guiducci, Serena, Walker, Ulrich, Jaeger, Veronika, Bannert, Bettina, Lapadula, Giovanni, Becvarare, Radim, Cutolo, Maurizio, Valentini, Gabriele, Siegert, Elise, Rednic, Simona, Montecucco, C., Carreira, Patricia E., Novak, Srdan, Czirjak, Laszlo, Varju, Cecilia, Chizzolini, Carlo, Allai, Daniela, Kucharz, Eugene J., Cozzi, Franco, Rozman, Blaz, Mallia, Carmel, Gabrielli, Armando, Bancel, Dominique Farge, Airo, Paolo, Hesselstrand, Roger, Martinovic, Duska, Balbir-Gurman, Alexandra, Braun-Moscovici, Yolanda, Hunzelmann, Nicolas, Pellerito, Raffaele, Caramaschi, Paola, Black, Carol, Damjanov, Nemanja, Henes, Joerg, Ortiz Santamaria, Vera, Heitmann, Stefan, Seidel, Matthias, Pereira Da Silva, Jose Antonio, Stamenkovic, Bojana, Selmi, Carlo Francesco, Tikly, Mohammed, Denisov, Lev N., Mueller-Ladner, Ulf, Engelhart, Merete, Hachulla, Eric, Riccieri, Valeria, Ionescu, Ruxandra Maria, Mihai, Carina, Sunderkoetter, Cord, Kuhn, Annegret, Schett, Georg, Distler, Joerg, Meroni, Pierluigi, Ingegnoli, Francesca, Mouthon, Luc, De Keyser, Filip, Smith, Vanessa, Cantatore, Francesco Paolo, Corrado, Ada, Ullman, Susanne, Iversen, Line, Pozzi, Maria Rosa, Eyerich, Kilian, Hein, Ruediger, Knott, Elisabeth, Wiland, Piotr, Szmyrka-Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Madej, Marta, Jose Alegre-Sancho, Juan, Krummel-Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Guenther, Claudia, Anne, Erler, Westhovens, Rene, De langhe, Ellen, Lenaerts, Jan, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Uprus, Maria, Otsa, Kati, Yavuz, Sule, Radominski, Sebastiao Cezar, Mueller, Carolina de Souza, Azevedo, Valderilio Feijo, Popa, Sergei, Zenone, Thierry, Stebbings, Simon, Highton, John, Mathieu, Alessandro, Vacca, Alessandra, Stamp, Lisa, Chapman, Peter, O'Donnell, John, Solanki, Kamal, Doube, Alan, Veale, Douglas, O'Rourke, Marie, Loyo, Esthela, Li, Mengtao, Rosato, Edoardo, Amoroso, Antonio, Gigante, Antonietta, Oksel, Fahrettin, Yargucu, Figen, Tanaseanu, Cristina-Mihaela, Popescu, Monica, Dumitrascu, Alina, Tiglea, Isabela, Foti, Rosario, Visalli, Elisa, Benenati, Alessia, Amato, Giorgio, Ancuta, Codrina, Chirieac, Rodica, Villiger, Peter, Adler, Sabine, Dan, Diana, de la Pena Lefebvre, Paloma Garcia, Rodriguez Rubio, Silvia, Valero Exposito, Marta, Sibilia, Jean, Chatelus, Emmanuel, Gottenberg, Jacques Eric, Chifflot, Helene, Litinsky, Ira, Del Galdo, Francesco, Venalis, Algirdas, Saketkoo, Lesley Ann, Lasky, Joseph A., Kerzberg, Eduardo, Montoya, Fabiana, Cosentino, Vanesa, Limonta, Massimiliano, Brucato, Antonio Luca, Lupi, Elide, Spertini, Francois, Ribi, Camillo, Buss, Guillaume, Martin, Thierry, Guffroy, Aurelien, Poindron, Vincent, Chung, Lori, Schmeiser, Tim, Zebryk, Pawel, Riso, Nuno, Riemekasten, Gabriela, Rezus, Elena, Puttini, Piercarlo Sarzi, Ege Üniversitesi, University of Zurich, Distler, Oliver, Chizzolini, Carlo, Allai, Daniela, Becker, M., Graf, N., Sauter, R., Allanore, Y., Curram, J., Denton, C. P., Khanna, D., Matucci-Cerinic, M., de Oliveira Pena, J., Pope, J. E., Distler, O., Guiducci, S., Walker, U., Jaeger, V., Bannert, B., Lapadula, G., Becvarare, R., Cutolo, M., Valentini, G., Siegert, E., Rednic, S., Montecucco, C., Carreira, P. E., Novak, S., Czirjak, L., Varju, C., Chizzolini, C., Allai, D., Kucharz, E. J., Cozzi, F., Rozman, B., Mallia, C., Gabrielli, A., Bancel, D. F., Airo, P., Hesselstrand, R., Martinovic, D., Balbir-Gurman, A., Braun-Moscovici, Y., Hunzelmann, N., Pellerito, R., Caramaschi, P., Black, C., Damjanov, N., Henes, J., Santamaria, V. O., Heitmann, S., Seidel, M., Pereira Da Silva, J. A., Stamenkovic, B., Selmi, C. F., Tikly, M., Denisov, L. N., Muller-Ladner, U., Engelhart, M., Hachulla, E., Riccieri, V., Ionescu, R. M., Mihai, C., Sunderkotter, C., Kuhn, A., Schett, G., Distler, J., Meroni, P., Ingegnoli, F., Mouthon, L., De Keyser, F., Smith, V., Cantatore, F. P., Corrado, A., Ullman, S., Iversen, L., Pozzi, M. R., Eyerich, K., Hein, R., Knott, E., Wiland, P., Szmyrka-Kaczmarek, M., Sokolik, R., Morgiel, E., Madej, M., Alegre-Sancho, J. J., Krummel-Lorenz, B., Saar, P., Aringer, M., Gunther, C., Anne, E., Westhovens, R., De Langhe, E., Lenaerts, J., Anic, B., Baresic, M., Mayer, M., Uprus, M., Otsa, K., Yavuz, S., Radominski, S. C., de Souza Muller, C., Azevedo, V. F., Popa, S., Zenone, T., Stebbings, S., Highton, J., Mathieu, A., Vacca, A., Stamp, L., Chapman, P., O'Donnell, J., Solanki, K., Doube, A., Veale, D., O'Rourke, M., Loyo, E., Li, M., Rosato, E., Amoroso, A., Gigante, A., Oksel, F., Yargucu, F., Tanaseanu, C. -M., Popescu, M., Dumitrascu, A., Tiglea, I., Foti, R., Visalli, E., Benenati, A., Amato, G., Ancuta, C., Chirieac, R., Villiger, P., Adler, S., Dan, D., de la Pena Lefebvre, P. G., Rubio, S. R., Exposito, M. V., Sibilia, J., Chatelus, E., Gottenberg, J. E., Chifflot, H., Litinsky, I., Del Galdo, F., Venalis, A., Saketkoo, L. A., Lasky, J. A., Kerzberg, E., Montoya, F., Cosentino, V., Limonta, M., Brucato, A. L., Lupi, E., Spertini, F., Ribi, C., Buss, G., Martin, T., Guffroy, A., Poindron, V., Chung, L., Schmeiser, T., Zebryk, P., Riso, N., Riemekasten, G., Rezus, E., and Sarzi Puttini, P.
Subjects: INVOLVEMENT, SELECTION, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, diffuse, predictive factors, systemic sclerosis, 2745 Rheumatology, epidemiologic methods, morbidity, Disease, Immunology, General Biochemistry, Genetics and Molecular Biology, Immunology and Allergy, Rheumatology, INTERSTITIAL LUNG-DISEASE, disease worsening, mortality, predictive factors, systemic sclerosis, predictive factor, disease worsening, DESIGN, middle aged, Medicine and Health Sciences, FIBROSIS, scleroderma, SKIN THICKNESS SCORE, mortality, skin and connective tissue diseases, Prospective cohort study, humans, lung diseases, ddc:616, education.field_of_study, heart diseases, integumentary system, clinical trials as topic, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, 10051 Rheumatology Clinic and Institute of Physical Medicine, Interstitial lung disease, follow-up studies, ddc, female, Cohort, 2723 Immunology and Allergy, europe, Life Sciences & Biomedicine, CLINICAL-TRIALS, survival rate, medicine.medical_specialty, Population, 610 Medicine & health, disease progression, male, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Severity of illness, REGRESSION, medicine, severity of illness index, education, Survival rate, METAANALYSIS, 2403 Immunology, Science & Technology, Scleroderma, Systemic, business.industry, MORTALITY, systemic, medicine.disease, prospective studies, Clinical trial, prognosis, scleroderma, diffuse, scleroderma, systemic, Scleroderma, Diffuse, business
Abstract: PubMed: 31227488, Objectives Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database. Methods Inclusion criteria were diagnosis of diffuse SSc and follow-up over 12±3 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression. Results Of 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model. Conclusions The use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trials. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ., Bayer Bayer, United Kingdom Université Paris Descartes Li Ka Shing Foundation, LKSF University of Michigan, U-M, 1Department of Rheumatology and the Centre of experimental Rheumatology, University Hospital Zurich, Zurich, switzerland 2Graf Biostatistics, Winterthur, switzerland 3Big Data institute, li Ka shing Centre for Health information and Discovery, nuffield Department of Medicine, University of Oxford, Oxford, UK 4Rheumatology a Department, Paris Descartes University, sorbonne Paris Cité, Cochin Hospital, Paris, France 5Data science and analytics, Bayer plc, Reading, UK 6UCl Division of Medicine, Royal Free Campus, london, UK 7Division of Rheumatology, Department of internal Medicine, University of Michigan scleroderma Program, University of Michigan, ann arbor, Michigan, Usa 8Department of experimental and Clinical Medicine, University of Florence, Florence, italy 9Bayer Us llC, Whippany, new Jersey, Usa 10Department of Medicine, Division of Rheumatology, University of Western Ontario, st. Joseph’s Health Care, london, Ontario, Canada Acknowledgements The R-code for the linear Mi-lassO was received from Qixuan Chen.21 Medical writing assistance was provided by adelphi Communications ltd (Bollington, UK), funded by Bayer aG (Berlin, Germany)., Contributors study conception and design, acquisition of data, analysis and interpretation of data and drafting and revising the article: OD and MB; analysis and interpretation of data: OD, MB, Rs and nG. all authors have critically reviewed and approved the final submitted version to be published. Funding This study was supported by a grant from Bayer aG. Bayer employees are coauthors of this paper and supported the study design and interpretation of the data, but otherwise Bayer had no influence on the study., Competing interests MOB declares no conflict of interest. OD has had consultancy relationships with actelion, Bayer, Biogen idec, Boehringer ingelheim, Chemomab, espeRare foundation, Genentech/Roche, GsK, inventiva, italfarmaco, lilly, medac, Medimmune, Mitsubishi Tanabe Pharma, Pharmacyclics, novartis, Pfizer, sanofi, sinoxa and UCB in the area of potential treatments of scleroderma and its complications. OD has received research funding from actelion, Bayer, Boehringer ingelheim, Mitsubishi Tanabe Pharma and Roche in the area of potential treatments of scleroderma and its complications. OD has a patent for mir-29 licensed for the treatment of systemic sclerosis. DK has consultancy relationships and/or has received grant/research support from Bayer, Bristol-Myers squibb, Boehringer ingelheim, Genentech/Roche, niH, Pfizer, sanofi-aventis Pharmaceuticals, actelion Pharmaceuticals Us, Chemomab, Corbus, Covis, Cytori, eicos, eMD serono, Gilead, GlaxosmithKline, and UCB Pharma. He is a shareholder of eicos. CPD has consultancy relationships with and/or has received speakers’ bureau fees from actelion Pharmaceuticals Us, Bayer aG, GlaxosmithKline, Csl Behring, Merck serono, Roche Pharmaceuticals, Genentech and Biogen iDeC inc., inventiva, sanofi-aventis Pharmaceuticals and Boehringer ingelheim. JeP has consultancy relationships with and/or has received grant/research support from actelion, Bayer aG, Bristol-Myers squibb, Merck, Pfizer inc. and Roche. MM-C has consultancy relationships and/ or has received grant/research support from Pfizer, Bristol-Myers squibb, actelion, UCB Pharma, Bayer, Chemomab, Genentech/Roche, inventiva and lilly. Ya has consultancy relationships with and/or has received grant/research support from actelion, Pharmaceuticals Us, Bayer aG, Bristol-Myers squibb, inventiva, Medac, Pfizer inc., Roche Pharmaceuticals, Genentech and Biogen iDeC inc., sanofi-aventis Pharmaceuticals and servier. JdOP and JC are employees of Bayer. nTG has nothing to disclose.
Published: 2019

29. Classification, categorization and essential items for digital ulcer evaluation in systemic sclerosis: a DeSScipher/European Scleroderma Trials and Research group (EUSTAR) survey

Author: Blagojevic, Jelena, Bellando-Randone, Silvia, Abignano, Giuseppina, Avouac, Jérôme, Cometi, L, Czirják, László, Denton, Christopher P, Distler, Oliver, Frerix, Marc, Guiducci, Serena, Huscher, Dörte, Jaeger, Veronika K, Lóránd, Veronika, Maurer, Britta, Nihtyanova, Svetlana, Riemekasten, Gabriela, Siegert, Elise, Tarner, Ingo H, Vettori, Serena, Walker, Ulrich A, Allanore, Yannick, Müller-Ladner, Ulf, Del Galdo, Francesco, Matucci-Cerinic, Marco, EUSTAR co-workers, University of Zurich, Blagojevic, Jelena, Blagojevic, J., Bellando-Randone, S., Abignano, G., Avouac, J., Cometi, L., Czirják, L., Denton, C. P., Distler, O., Frerix, M., Guiducci, S., Huscher, D., Jaeger, V. K., Lóránd, V., Maurer, B., Nihtyanova, S., Riemekasten, G., Siegert, E., Tarner, I. H., Vettori, S., Walker, U. A., Allanore, Y., Müller-Ladner, U., Del Galdo, F., and Matucci-Cerinic, M.
Subjects: 0301 basic medicine, Male, lcsh:Diseases of the musculoskeletal system, Observational Trial, 2745 Rheumatology, Digital ulcer, Categorisation, Scleroderma, Systemic sclerosi, 0302 clinical medicine, Surveys and Questionnaires, Immunology and Allergy, Prospective Studies, 10051 Rheumatology Clinic and Institute of Physical Medicine, Digital ulcers, Middle Aged, Calcium Channel Blockers, Classification, 3. Good health, Clinical Practice, Categorization, 2723 Immunology and Allergy, Systemic sclerosis, Drug Therapy, Combination, Female, Research Article, Adult, medicine.medical_specialty, Immunology, 610 Medicine & health, Sildenafil Citrate, Fingers, 03 medical and health sciences, Rheumatology, Skin Ulcer, medicine, Humans, In patient, European Union, Iloprost, 030203 arthritis & rheumatology, 2403 Immunology, Scleroderma, Systemic, business.industry, Bosentan, Essential item, medicine.disease, 030104 developmental biology, Essential items, Physical therapy, Observational study, lcsh:RC925-935, business
Abstract: Background: A consensus on digital ulcer (DU) definition in systemic sclerosis (SSc) has been recently reached (Suliman et al., J Scleroderma Relat Disord 2:115-20, 2017), while for their evaluation, classification and categorisation, it is still missing. The aims of this study were to identify a set of essential items for digital ulcer (DU) evaluation, to assess if the existing DU classification was useful and feasible in clinical practice and to investigate if the new categorisation was preferred to the simple distinction of DU in recurrent and not recurrent, in patients with systemic sclerosis (SSc).Methods: DeSScipher is the largest European multicentre study on SSc. It consists of five observational trials (OTs), and one of them, OT1, is focused on DU management. The DeSScipher OT1 items on DU that reached ≥ 60% of completion rate were administered to EUSTAR (European Scleroderma Trials and Research group) centres via online survey. Questions about feasibility and usefulness of the existing DU classification (DU due to digital pitting scars, to loss of tissue, derived from calcinosis and gangrene) and newly proposed categorisation (episodic, recurrent and chronic) were also asked.Results: A total of 84/148 (56.8%) EUSTAR centres completed the questionnaire. DeSScipher items scored by ≥ 70% of the participants as essential and feasible for DU evaluation were the number of DU defined as a loss of tissue (level of agreement 92%), recurrent DU (84%) and number of new DU (74%). For 65% of the centres, the proposed classification of DU was considered useful and feasible in clinical practice. Moreover, 80% of the centres preferred the categorisation of DU in episodic, recurrent and chronic to simple distinction in recurrent/not recurrent DU.Conclusions: For clinical practice, EUSTAR centres identified only three essential items for DU evaluation and considered the proposed classification and categorisation as useful and feasible. The set of items needs to be validated while further implementation of DU classification and categorisation is warranted.Trial registration: Observational trial on DU (OT1) is one of the five trials of the DeSScipher project (ClinicalTrials.gov; OT1 Identifier: NCT01836263, posted on April 19, 2013).
Published: 2018

30. Differences associated with age at onset in early systemic sclerosis patients: a report from the EULAR Scleroderma Trials and Research Group (EUSTAR) database

Author: José Luis Andreu, Alexandra Balbir-Gurman, Roger Hesselstrand, Simona Rednic, Mohammed Tikly, G. Riemekasten, Paola Caramaschi, Serena Vettori, Marco Matucci-Cerinic, Dominique Farge, Yannick Allanore, Nemanja Damjanov, L. Czirják, Ada Corrado, Beatriz Joven, Loreto Carmona, Estíbaliz Loza, Paolo Airò, Ulrich A. Walker, Oliver Distler, Patricia Carreira, Lidiya P. Ananieva, Carreira, Pe, Carmona, L, Joven, Be, Loza, E, Andréu, Jl, Riemekasten, G, Vettori, S, Balbir-Gurman, A, Airò, P, Walker, U, Damjanov, N, Matucci-Cerinic, M, Ananieva, Lp, Rednic, S, Czirják, L, Distler, O, Farge, D, Hesselstrand, R, Corrado, A, Caramaschi, P, Tikly, M, and Allanore, Y
Subjects: Adult, Male, medicine.medical_specialty, Databases, Factual, Cross-sectional study, Immunology, Disease, Scleroderma, 03 medical and health sciences, Age Distribution, 0302 clinical medicine, Rheumatology, Internal medicine, Cardiac conduction, Prevalence, medicine, Humans, Immunology and Allergy, Registries, 030212 general & internal medicine, Age of Onset, Sex Distribution, skin and connective tissue diseases, Retrospective Studies, 030203 arthritis & rheumatology, Scleroderma, Systemic, integumentary system, business.industry, Incidence, Incidence (epidemiology), Age Factors, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, 3. Good health, Europe, Cross-Sectional Studies, Female, Age of onset, business
Abstract: Objective: The aim of this study was to analyse differences in clinical presentation in patients with early (< 3 years’ duration) systemic sclerosis (SSc), comparing three age groups according to disease subsets. Method: Cross-sectional analysis of the prospective EULAR Scleroderma Trials and Research database (EUSTAR) was performed. Patients fulfilling preliminary American College of Rheumatology 1980 classification criteria for SSc, with < 3 years from the first non-Raynaud’s SSc symptom at first entry, were selected. Patients with < 3 years from the first SSc symptom, including Raynaud’s phenomenon, were also analysed. SSc-related variables, including antibodies, SSc subsets, and organ involvement, were examined. Age was categorized into ≤ 30, 31–59, and ≥ 60 years. We performed descriptive and bivariate analyses. Results: The study included 1027 patients: 90% Caucasian, 80% women, and 40% with diffuse disease. In early stages of SSc, younger patients had significantly more anti-Scl-70 antibodies and diffuse disease. With increasing age, we observed more elevation of estimated pulmonary systolic pressure on echocardiography (5%, 13%, and 30%, respectively, in the three age groups), cardiac conduction blocks (6%, 6%, and 15%), and left ventricular diastolic dysfunction (4%, 12%, and 27%). The results were similar for 650 patients with < 3 years from first SSc symptom, including Raynaud’s. Conclusion: In early stages of SSc, older patients showed data indicating more severe disease with greater cardiac involvement. The diffuse subset was more frequent in the younger subgroup. The identification of such differences may help in selecting appropriate management for individual patients in clinical practice. (Less)
Published: 2018

31. A gender gap in primary and secondary heart dysfunctions in systemic sclerosis: a EUSTAR prospective study

Author: Antonio C. Zea Mendoza, Jean Sibilia, Kamal Solanki, Cristina Mihaela Tanaseanu, Fredrick M. Wigley, Guido Valesini, M. Govoni, Lisa K. Stamp, Christopher P. Denton, Yolanda Braun-Moscovici, Ruxandra Ionescu, Øyvind Midtvedt, Ileana Nicoara, Aleksandra Stanković, Rüdiger Hein, Alina Dumitrascu, Susanne Ullman, Alan Tyndall, Sergio A. Jimenez, Irena Butrimiene, Alan Doube, Eugene J. Kucharz, Mohammed Tikly, Pier Luigi Meroni, Simon Stebbings, Renata Sokolik, Alexandra Balbir Gurman, Roger Hesselstrand, Kirsten Damgaard, Francesco Paolo Cantatore, Razvan Ionitescu, Silvana Zeni, Marco Matucci-Cerinic, Maria Rosa Pozzi, Jacques-Eric Gottenberg, Srdan Novak, Ana Maria Gherghe, David Launay, Liliana Groppa, Carlomaurizio Montecucco, Roxana Sfrent Cornateanu, Stefan Heitmann, Paloma García de la Peña Lefebvre, Daniela Opris, Peter T. Chapman, Line V. Iversen, Bernard Coleiro, Ulf Müller-Ladner, John Highton, Mara Oleszowsky, Gabriella Szücs, Magdalena Kopec-Medrek, Carlos De La Puente Buijdos, Paola Caramaschi, Magdalena Szmyrka-Kaczmarek, Rucsandra Dobrota, Gabriele Valentini, Fabiana Montoya, Blaz Rozman, Alberto Sulli, Hélène Chifflot, Raffaella Scorza, Patricia Carreira, Paulius Venalis, Lisa Maria Bambara, Torhild Garen, Isabela Tiglea, Agneta Scheja, Duska Martinovic, Jörg H W Distler, Jörg Henes, Giovanni Lapadula, Luc Mouthon, Diana Karpec, Douglas J. Veale, Valeria Riccieri, Nicolas Hunzelmann, Muriel Elhai, Serena Guiducci, Codrina Ancuta, Simonetta Pisarri, Thierry Zenone, Esthela Loyo, Branimir Anić, Claudia Günther, R. Becvar, Eugen Russu, Serena Vettori, Carlo Chizzolini, Vanessa Smith, Mengtao Li, Stanislaw Sierakowsky, Carmel Mallia, Małgorzata Widuchowska, Carolina de Souza Müller, László Czirják, Algirdas Venalis, Adrian Hij, Marta Valero Exposito, Simona Rednic, Miroslav Mayer, Laura Groseanu, Walter Alberto Sifuentes Giraldo, Murray Baron, Dominique Farge, Anna Kotulska, Marko Baresic, Svetlana Agachi, Martin Aringer, Merete Engelhart, John L. O'Donnell, Jérôme Avouac, Filip De Keyser, Ulrich A. Walker, Roberto Caporali, Harald Burkhardt, P. G. Vlachoyiannopoulos, Maurizio Cutolo, Frank A. Wollheim, Edoardo Rosato, Suzanne Kafaja, Valderílio Feijó Azevedo, Kilian Eyerich, Paolo Airò, Emmanuel Chatelus, L. Ananieva, Ira Litinsky, Andrea Lo Monaco, Vanesa Cosentino, Rita Rugiene, Eric Hachulla, P. Saar, Bojana Stamenkovic, Brigitte Krummel-Lorenz, Yannick Allanore, Elisabeth Knott, Oliver Distler, Matthias Seidel, Silvia Rodriguez Rubio, Franco Cozzi, Mihai Bojinca, Nemanja Damjanov, Maria João Salvador, Joanna Busquets, Otylia Kowal Bielecka, André Kahan, Jacek Szechiński, Daniel E. Furst, C. Mihai, Rodica Chirieac, Ewa Morgiel, Georg Schett, Armando Gabrielli, Giovanna Cuomo, Piotr Wiland, Maya N. Starovoytova, Sebastião Cezar Radominski, Gitte Strauss, Lealea Chiaburu, Florenzo Iannone, Carol M. Black, Andrea Himsel, Eduardo Kerzberg, Cecília Varjú, Vera Ortiz Santamaria, Gabriela Riemekasten, Dorota Krasowska, Marilena Gorga, Monica Popescu, Marie O'Rourke, Henrik Nielsen, Raffaele Pellerito, Ada Corrado, Elhai, M, Avouac, J, Walker, Ua, Matucci Cerinic, M, Riemekasten, G, Airò, P, Hachulla, E, Valentini, Gabriele, Carreira, Pe, Cozzi, F, Balbir Gurman, A, Braun Moscovici, Y, Damjanov, N, Ananieva, Lp, Scorza, R, Jimenez, S, Busquets, J, Li, M, Müller Ladner, U, Kahan, A, Distler, O, Allanore, Y, EUSTAR co, Author, EUSTAR co, Authors, Matucci-Cerinic, M, Airo, P, Valentini, G, Gurman, Ab, Braun-Moscovici, Y, Mt, Li, Muller-Ladner, U, Allanore, Y EUSTAR co-authors: Serena Guiducci, Alan, Tyndall, Giovanni, Lapadula, Florenzo, Iannone, Radim, Becvar, Stanislaw, Sierakowsky, Otylia Kowal Bielecka, Maurizio, Cutolo, Alberto, Sulli, Cuomo, Giovanna, Vettori, Serena, Simona, Rednic, Ileana, Nicoara, Vlachoyiannopoulos, P, Montecucco, C, Roberto, Caporali, Srdan, Novak, László, Czirják, Cecilia, Varju, Carlo, Chizzolini, Eugene, J Kucharz, Anna, Kotulska, Magdalena, Kopec-Medrek, Malgorzata, Widuchowska, Blaz, Rozman, Carmel, Mallia, Bernard, Coleiro, Armando, Gabrielli, Dominique, Farge, Adrian, Hij, Roger, Hesselstrand, Agneta, Scheja, Frank, Wollheim, Duska, Martinovic, Govoni, M, Andrea Lo Monaco, Nicolas, Hunzelmann, Raffaele, Pellerito, Lisa Maria Bambara, Paola, Caramaschi, Carol, Black, Christopher, Denton, Jörg, Hene, Vera Ortiz Santamaria, Stefan, Heitmann, Dorota, Krasowska, Matthias, Seidel, Mara, Oleszowsky, Harald, Burkhardt, Andrea, Himsel, Maria, J Salvador, Bojana, Stamenkovic, Aleksandra, Stankovic, Mohammed, Tikly, Maya, N Starovoytova, Merete, Engelhart, Gitte, Strau, Henrik, Nielsen, Kirsten, Damgaard, Gabriella, Szüc, Antonio Zea Mendoza, Carlos de la Puente Buijdos, Walter, A Sifuentes Giraldo, Øyvind, Midtvedt, Torhild, Garen, David, Launay, Guido, Valesini, Valeria, Riccieri, Ruxandra Maria Ionescu, Daniela, Opri, Laura, Groseanu, Fredrick, M Wigley, Carmen, M Mihai, Roxana Sfrent Cornateanu, Razvan, Ionitescu, Ana Maria Gherghe, Marilena, Gorga, Rucsandra, Dobrota, Mihai, Bojinca, Georg, Schett, Jörg Hw Distler, Pierluigi, Meroni, Silvana, Zeni, Luc, Mouthon, Filip De Keyser, Vanessa, Smith, Francesco, P Cantatore, Ada, Corrado, Susanne, Ullman, Line, Iversen, Maria, R Pozzi, Kilian, Eyerich, Rüdiger, Hein, Elisabeth, Knott, Jacek, Szechinski, Piotr, Wiland, Magdalena, Szmyrka-Kaczmarek, Renata, Sokolik, Ewa, Morgiel, Brigitte, Krummel-Lorenz, Petra, Saar, Martin, Aringer, Claudia, Günther, Branimir, Anic, Marko, Baresic, Miroslav, Mayer, Sebastião, C Radominski, Carolina de Souza Müller, Valderílio, F Azevedo, Svetlana, Agachi, Liliana, Groppa, Lealea, Chiaburu, Eugen, Russu, Thierry, Zenone, Simon, Stebbing, John, Highton, Lisa, Stamp, Peter, Chapman, Murray, Baron, John, O'Donnell, Kamal, Solanki, Alan, Doube, Douglas, Veale, Marie, O'Rourke, Esthela, Loyo, Edoardo, Rosato, Simonetta, Pisarri, Cristina-Mihaela, Tanaseanu, Monica, Popescu, Alina, Dumitrascu, Isabela, Tiglea, Rodica, Chirieac, Codrina, Ancuta, Daniel, E Furst, Suzanne, Kafaja, Paloma García de la Peña Lefebvre, Silvia Rodriguez Rubio, Marta Valero Exposito, Jean, Sibilia, Emmanuel, Chatelu, Jacques Eric Gottenberg, Hélène, Chifflot, Ira, Litinsky, Algirdas, Venali, Irena, Butrimiene, Paulius, Venali, Rita, Rugiene, Diana, Karpec, Eduardo, Kerzberg, Fabiana, Montoya, Vanesa, Cosentino, and Chizzolini, Carlo
Subjects: 0301 basic medicine, Male, heart dysfunction, Databases, Factual, Epidemiology, autoimmune diseases, epidemiology, systemic sclerosis, Kaplan-Meier Estimate, 0302 clinical medicine, Cardiovascular Disease, Immunology and Allergy, Prospective Studies, Age of Onset, skin and connective tissue diseases, Prospective cohort study, ddc:616, Orvostudományok, Middle Aged, Prognosis, Connective tissue disease, 3. Good health, Europe, Cardiovascular Diseases, Cohort, Disease Progression, Female, Autoimmune Diseases, Systemic Sclerosis, Human, Adult, medicine.medical_specialty, Prognosi, Immunology, Socio-culturale, Klinikai orvostudományok, Autoimmune Disease, General Biochemistry, Genetics and Molecular Biology, Follow-Up Studie, 03 medical and health sciences, Sex Factors, Rheumatology, Internal medicine, medicine, Humans, Sex Distribution, Systemic Sclerosi, Aged, 030203 arthritis & rheumatology, Lupus erythematosus, Scleroderma, Systemic, business.industry, medicine.disease, Pulmonary hypertension, Prospective Studie, 030104 developmental biology, Heart failure, Age of onset, business, Follow-Up Studies
Abstract: OBJECTIVES: In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly known. Therefore, we aimed to determine sex effects on outcomes. METHOD: We performed a prospective observational study using the latest 2013 data extract from the EULAR scleroderma trials and research (EUSTAR) cohort. We looked at (i) sex influence on disease characteristics at baseline and (ii) then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival. RESULTS: 9182 patients with SSc were available (1321 men) for the baseline analyses. In multivariate analysis, male sex was independently associated with a higher risk of diffuse cutaneous subtype (OR: 1.68, (1.45 to 1.94); p
Published: 2014

32. The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis

Author: F David Carmona, Jose-Ezequiel Martin, Lorenzo Beretta, Carmen P Simeón, Patricia E Carreira, José Luis Callejas, Mónica Fernández-Castro, Luis Sáez-Comet, Emma Beltrán, María Teresa Camps, María Victoria Egurbide, Spanish Scleroderma Group, Paolo Airó, Raffaella Scorza, Claudio Lunardi, Nicolas Hunzelmann, Gabriela Riemekasten, Torsten Witte, Alexander Kreuter, Jörg H W Distler, Rajan Madhok, Paul Shiels, Jacob M van Laar, Carmen Fonseca, Christopher Denton, Ariane Herrick, Jane Worthington, Annemie J Schuerwegh, Madelon C Vonk, Alexandre E Voskuyl, Timothy R D J Radstake, Javier Martín, Rheumatology, CCA - Disease profiling, The Spanish Scleroderma Group, [Carmona,FD, Martín JE] Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain. [ Beretta,L, Scorza,R] Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, University of Milan, Italy. [ Carmen,P S] Department of Internal Medicine, Hospital Vall d’Hebron, Barcelona, Spain. [Carreira,P E] Department of Rheumatology, Hospital 12 de Octubre, Madrid, Spain. [Callejas,J.L. ] Department of Internal Medicine, Hospital Clínico San Cecilio, Granada, Spain. [Fernández-Castro,M.] Department of Rheumatology, Hospital Puerta de Hierro Majadahonda, Madrid, Spain. [Sáez-Comet,L] Department of Internal Medicine, Hospital Universitario Miguel Servet, Zaragoza, Spain. [Beltran,E.] Department of Rheumatology, Hospital General Universitario de Valencia, Spain. [Camps,MT.] Department of Internal Medicine, Hospital Carlos Haya, Málaga, Spain. [Egurbide,M.V.] Department of Internal Medicine, Hospital de Cruces, Barakaldo, Spain. [Airo,P.] Servizio di Reumatologia ed Immunologia Clinica Spedali Civili, Brescia, Italy. [Lunardi,C] Department of Medicine, Universita` degli Studi di Verona, Verona, Italy. [Hunzelmann, N] Department of Dermatology, University of Cologne, Cologne, Germany. [Riemekasten,G] Department of Rheumatology and Clinical Immunology, Charite´ University Hospital, Berlin, Germany. [Witte,T] Hannover Medical School, Hannover, Germany. [Kreuter,A] Ruhr University of Bochum, Germany. [Distler,JHW] Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany. [Madhok,R, Shiels,P] Centre for Rheumatic Diseases, Glasgow Royal Infirmary, University of Glasgow, United Kingdom. [Van Laar,JM] Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom. [Fonseca,C, Denton,C] Centre for Rheumatology, Royal Free and University College Medical School, London, United Kingdom. [Herrick,A, Worthington, J] Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom. [Schuerwegh,AJ] Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. [Vonk,MC, Radstake,T.R.D] Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. [Voskuyl,AE] Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands. [Radstake,T.R.D] Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, The Netherland., and 17552, Arthritis Research UK, United Kingdom
Subjects: Male, Linkage disequilibrium, Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings], Polimorfismo de nucleótido simple, SLE, lcsh:Medicine, Autoimmunity, Genome-wide association study, Linkage Disequilibrium, Scleroderma, Phenomena and Processes::Genetic Phenomena::Genotype::Haplotypes [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Gene Frequency, Named Groups::Persons::Population Groups::Continental Population Groups::European Continental Ancestry Group [Medical Subject Headings], Risk Factors, IRF5, Genetics of the Immune System, Lupus Erythematosus, Systemic, Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Scleroderma, Systemic [Medical Subject Headings], skin and connective tissue diseases, lcsh:Science, Multidisciplinary, Diseases::Immune System Diseases::Autoimmune Diseases::Lupus Erythematosus, Systemic [Medical Subject Headings], Predisposición genética a la enfermedad, Phenomena and Processes::Genetic Phenomena::Genetic Linkage::Linkage Disequilibrium [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease [Medical Subject Headings], Phenotype, Interferon Regulatory Factors, SYSTEMIC SCLEROSIS, Medicine, Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2], Female, TYPE I INTERFERON, Haplotipos, Research Article, Factores de riesgo, Immunology, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Adaptor Proteins, Signal Transducing::Interferon Regulatory Factors [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Health Care::Environment and Public Health::Public Health::Epidemiologic Factors::Causality::Risk Factors [Medical Subject Headings], Single-nucleotide polymorphism, Human leukocyte antigen, Biology, Polymorphism, Single Nucleotide, White People, Autoimmune Diseases, Rheumatology, Lupus eritematoso sistémico, Genetics, Humans, Genetic Predisposition to Disease, Grupo de ascendencia continental europea, Allele, Allele frequency, Alleles, Genetic Association Studies, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings], Scleroderma, Systemic, Haplotype, lcsh:R, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genetic Loci [Medical Subject Headings], Human Genetics, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic [Medical Subject Headings], Factores reguladores del interferón, Haplotypes, Desequilibrio de ligamiento, Check Tags::Female [Medical Subject Headings], Genetic Loci, Genetics of Disease, Genetic Polymorphism, Clinical Immunology, lcsh:Q, Phenomena and Processes::Genetic Phenomena::Gene Frequency [Medical Subject Headings], Population Genetics
Abstract: Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34×10-8, OR = 1.22, CI 95% = 1.14-1.30; rs2004640: P = 4.60×10-7, OR = 0.84, CI 95% = 0.78-0.90; rs10488631: P = 7.53×10-20, OR = 1.63, CI 95% = 1.47-1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04×10-22, OR = 1.75, CI 95% = 1.56-1.97) better explained the observed association (likelihood P-value = 1.48×10-4), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific. © 2013 Carmona et al.
Published: 2013

33. TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension: results from a multicentre EUSTAR study of European Caucasian patients

Author: Gilles Chiocchia, Marco Matucci-Cerinic, Otylia Kowal-Bielecka, Jean-Luc Cracowski, Ulrich A. Walker, Julien Wipff, Jörg H W Distler, Matthieu Bouaziz, László Czirják, Inga Melchers, Nicolas Hunzelmann, Elisabeth Diot, Daniele Cusi, Catherine Boileau, Sara Lupoli, Philippe Dieudé, Marc Humbert, Yannick Allanore, Giovanna Cuomo, H.-Erich Wichmann, G. Riemekasten, Ulf Müller-Ladner, Eric Hachulla, P. G. Vlachoyiannopoulos, Paola Caramaschi, Costanza Conti, Paolo Airò, Martina Müller-Nurasyid, Barbara Ruiz, Mickaël Guedj, Valeria Riccieri, Lucile Revillod, Franco Cozzi, Nemanja Damjanov, Vasiliki Kalliopi Bournia, Eugénie Koumakis, Kiet Tiev, Université Paris Descartes - Paris 5 (UPD5), Université Paris Diderot - Paris 7 (UPD7), Université d'Évry-Val-d'Essonne (UEVE), Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Université Paris-Sud - Paris 11 (UP11), Hôpital Antoine Béclère, Assistance Publique - Hôpitaux de Paris (AP-HP), Centre Chirurgical Marie Lannelongue (CCML), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Leibniz Association, Spedali Civil Brescia, University of Freiburg [Freiburg], Université de Lille, Droit et Santé, Università degli Studi di Milano [Milano] (UNIMI), Fdn Filarete, Partenaires INRAE, European League Against Rheumatism Scleroderma Trials and Research group (EUSTAR), Association des Sclerodermiques de France, INSERM, Agence Nationale pour la Recherche [R07094KS], Pfizer, Koumakis, E, Wipff, J, Dieudé, P, Ruiz, B, Bouaziz, M, Revillod, L, Guedj, M, Distler, Jh, Matucci Cerinic, M, Humbert, M, Riemekasten, G, Airo, P, Melchers, I, Hachulla, E, Cusi, D, Wichmann, He, Hunzelmann, N, Tiev, K, Caramaschi, P, Diot, E, Kowal Bielecka, O, Cuomo, Giovanna, Walker, U, Czirják, L, Damjanov, N, Lupoli, S, Conti, C, Müller Nurasyid, M, Müller Ladner, U, Riccieri, V, Cracowski, Jl, Cozzi, F, Bournia, Vk, Vlachoyiannopoulos, P, Chiocchia, G, Boileau, C, Allanore, Y., Università degli Studi di Firenze = University of Florence (UniFI), and Università degli Studi di Milano = University of Milan (UNIMI)
Subjects: Genetics and Molecular Biology (all), Male, Systemic disease, Candidate gene, DNA Mutational Analysis, Biochemistry, DISEASE, Scleroderma, 0302 clinical medicine, Medizinische Fakultät, Transforming Growth Factor beta, Receptors, Immunology and Allergy, Familial Primary Pulmonary Hypertension, [MATH]Mathematics [math], skin and connective tissue diseases, 0303 health sciences, biology, integumentary system, arterial pulmonary hypertension, Pulmonary, Single Nucleotide, ASSOCIATION, Connective tissue disease, 3. Good health, Hypertension, Female, systemic sclerosi, Genotype, Hypertension, Pulmonary, European Continental Ancestry Group, Immunology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, White People, 03 medical and health sciences, Rheumatology, medicine, SNP, Humans, [INFO]Computer Science [cs], Genetic Predisposition to Disease, ddc:610, Polymorphism, HEREDITARY HEMORRHAGIC TELANGIECTASIA, Genotyping, ALK-1, 030304 developmental biology, 030203 arthritis & rheumatology, Scleroderma, Systemic, business.industry, MUTATIONS, Systemic, Receptors, Transforming Growth Factor beta, Biochemistry, Genetics and Molecular Biology (all), Transforming growth factor beta, medicine.disease, Pulmonary hypertension, BMPR2, biology.protein, business
Abstract: IntroductionSystemic sclerosis (SSc)-related pulmonary arterial hypertension (PAH) has emerged as a major mortality prognostic factor. Mutations of transforming growth factor beta (TGFβ) receptor genes strongly contribute to idiopathic and familial PAH.ObjectiveTo explore the genetic bases of SSc–PAH, we combined direct sequencing and genotyping of candidate genes encoding TGFβ receptor family members.Materials and methodsTGFβ receptor genes, BMPR2, ALK1, TGFR2 and ENG, were sequenced in 10 SSc–PAH patients, nine SSc and seven controls. In addition, 22 single-nucleotide polymorphisms (SNP) of these four candidate genes were tested for association in a first set of 824 French Caucasian SSc patients (including 54 SSc–PAH) and 939 controls. The replication set consisted of 1516 European SSc (including 219 SSc–PAH) and 3129 controls from the European League Against Rheumatism Scleroderma Trials and Research group network.ResultsNo mutation was identified by direct sequencing. However, two repertoried SNP, ENG rs35400405 and ALK1 rs2277382, were found in SSc–PAH patients only. The genotyping of 22 SNP including the latter showed that only rs2277382 was associated with SSc–PAH (p=0.0066, OR 2.13, 95% CI 1.24 to 3.65). Nevertheless, this was not replicated with the following result in combined analysis: p=0.123, OR 0.79, 95% CI 0.59 to 1.07.ConclusionsThis study demonstrates the lack of association between these TGFβ receptor gene polymorphisms and SSc–PAH using both sequencing and genotyping methods.
Published: 2012

34. Analysis of the association between CD40 and CD40 ligand polymorphisms and systemic sclerosis

Author: Teruel, María, Simeón Aznar, Carmen Pilar, Broen, Jasper C., Vonk, Madelon C., Carreira, Patricia, Camps García, María Teresa, García-Portales, Rosa, Delgado-Frías, Esmeralda, Gallego, Maria, Espinosa Garriga, Gerard, Spanish Scleroderma Study Group (SSSG), Beretta, Lorenzo, Airó, Paolo, Lunardi, Claudio, Riemekasten, Gabriela, Witte, Torsten, Krieg, Thomas, Kreuter, Alexander, Distler, Jörg H.V., Hunzelmann, Nicolas, Koeleman, Bobby P. C., Voskuyl, Alexandre E., Schuerwegh, Annemie J., González-Gay, Miguel A., Radstake, Timothy R.D.J., Martín, Javier, Narváez García, Francisco Javier, Rheumatology, CCA - Immuno-pathogenesis, Universitat de Barcelona, The Spanish Scleroderma Group, [Teruel,M, Martin,J] Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSICGranada, SpainArmilla (Granada), Spain. [Simeon,CP] Department of Internal Medicine, Hospital Valle de Hebron, Barcelona, Spain. [Broen,J, Vonk,MC] Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. [Carreira,P] Department of Rheumatology, Hospital 12 de Octubre, Madrid, Spain. [Camps,MT] Department of Internal Medicine, Hospital Carlos Haya, Málaga, Spain. [García-Portales,R] Department of Rheumatology, Hospital Virgen de la Victoria, Málaga, Spain. [Delgado-Frías,E] Department of Rheumatology, Hospital Universitario de Canarias, La Cuesta, San Cristóbal de La Laguna, Tenerife, Canarias, Spain. [Gallego,M] Department of Internal Medicine, Hospital Central de Asturias, Oviedo, Spain. [Espinosa,G] Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Spain. [Beretta,L] Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico. University of Milan, Milan, Italy. [Airó,P] Rheumatology Unit and Chair, Spedali Civili, Università degli Studi, Brescia, Italy. [Lunardi,C] Department of Medicine, Policlinico GB Rossi, Università degli studi di Verona, Verona, Italy. [Riemekasten,G] Department of Rheumatology and Clinical Immunology, Charité University Hospital and German Rheumatism Research Centre, a Leibniz Institute, Berlin, Germany. [Witte,T] Clinic for Immunology and Rheumatology Medical School, Hannover, Germany. [Krieg,T, and Hunzelmann,N] Department of Dermatology, University of Cologne, Germany. [Kreuter,A] Department of Dermatology, Allergology, and Venereology, Ruhr University of Bochum, Bochum, Germany. [Distler,JHW] Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany. [Koeleman,BP] Section Complex Genetics, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands. [Voskuy,AE] Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands. [Schuerwegh,AJ] Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. [González-Gay,MA] Department of Rheumatology, Hospital Universitario Marques de Valdecilla, IFIMAV, Santander, Spain. [Radstake,TRDJ] Department of Rheumatology and Clinical Immunology, University Utrecht Medical Center Utrecht, The Netherlands.
Subjects: systemic sclerosis, Autoimmune diseases, Genome-wide association study, CD40, CD40L, GWAS, Serology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Pulmonary fibrosis, Genotype, Immunology and Allergy, Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Scleroderma, Systemic [Medical Subject Headings], skin and connective tissue diseases, Giant cell arteritis, 0303 health sciences, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CD::Antigens, CD40 [Medical Subject Headings], Malalties autoimmunitàries, integumentary system, Predisposición genética a la enfermedad, Fibrosi pulmonar, Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease [Medical Subject Headings], Phenotype, Infection and autoimmunity Auto-immunity, transplantation and immunotherapy [NCMLS 1], Humanos, 3. Good health, 030220 oncology & carcinogenesis, Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2], Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Research Article, medicine.medical_specialty, Esclerodermia sistémica, Immunology, CD40 Ligand, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, 03 medical and health sciences, Rheumatology, Internal medicine, medicine, Humans, antígenos CD40, Genetic Predisposition to Disease, CD40 Antigens, Gene, Arteritis de cèl·lules gegants, 030304 developmental biology, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], Scleroderma, Systemic, business.industry, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CD::CD40 Ligand [Medical Subject Headings], medicine.disease, Ligando CD40, Scleroderma (Disease), Polimorfismo de Nucleótido Simple, Esclerodèrmia, business, Genotipo
Abstract: Introduction The aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc). Methods In total, 2,670 SSc patients and 3,245 healthy individuals from four European populations (Spain, Germany, The Netherlands, and Italy) were included in the study. Five single-nucleotide polymorphisms (SNPs) of CD40 (rs1883832, rs4810485, rs1535045) and CD40LG (rs3092952, rs3092920) were genotyped by using a predesigned TaqMan allele-discrimination assay technology. Meta-analysis was assessed to determine whether an association exists between the genetic variants and SSc or its main clinical subtypes. Results No evidence of association between CD40 and CD40LG genes variants and susceptibility to SSc was observed. Similarly, no significant statistical differences were observed when SSc patients were stratified by the clinical subtypes, the serologic features, and pulmonary fibrosis. Conclusions Our results do not suggest an important role of CD40 and CD40LG gene polymorphisms in the susceptibility to or clinical expression of SSc., This work was supported by the following grants. JM was funded by SAF2009-11110 from the Spanish Ministry of Science, by CTS-4977 and PI-0590-2010 from Junta de Andalucía, and by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), within the VI PN de I+D+i 2008-2011 (FEDER). T.R.D.J.R. was funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds). JM and TRDJR were sponsored by the Orphan Disease Program grant from the European League Against Rheumatism (EULAR). TW was awarded grants by DFG WI 1031/6.1 and DFG KFO 250 TP03. MT was supported by Spanish Ministry of Science through the program Juan de la Cierva (JCI-2010-08227).
Published: 2012

35. Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis

Author: Valeria Riccieri, László Czirják, Yannick Allanore, Jean-Luc Cracowski, Catherine Boileau, Inga Melchers, H.-Erich Wichmann, Jean-Charles Lambert, Oliver Meyer, Julien Wipff, Mohamad Saad, Jörg H W Distler, Luc Mouthon, Anne Marie Dupuy, Costanza Conti, Martina Müller, Nicolas Hunzelmann, Maria Martinez, Marco Matucci-Cerinic, Elisabeth Diot, Ulf Müller-Ladner, Paola Caramaschi, Otylia Kowal-Bielecka, André Kahan, Erika Salvi, G. Riemekasten, Arnold Munnich, Paolo Airò, Luc Letenneur, Eric Hachulla, Kiet Tiev, Barbara Ruiz, Daniele Cusi, Jérôme Avouac, Nemanja Damjanov, Philippe Dieudé, Gabriele Valentini, Philippe Amouyel, Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine 3, Institute for Clinical Immunology Erlangen-Nuremberg, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Departments of Medicine, Biomedicine & Rheumatology, Università degli Studi di Firenze = University of Florence (UniFI)-Division of Rheumatology AOUC - Denothe Centre, Department of Rheumatology and Clinical Immunology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Rheumatology and Clinical Immunology, Spedali Civili, Clinical Research Unit for Rheumatology, Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), Service de médecine interne, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Medicine, Surgery, and Dentistry, University of Milano, Genomics and Bioinformatics Platform, Fondazione Filarete, Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München (LMU)-Chair of Epidemiology, Institute of Epidemiology I, Helmholtz Zentrum München = German Research Center for Environmental Health, Department of Dermatology, University of Cologne, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Rheumatology Unit, Università degli studi di Verona = University of Verona (UNIVR), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Rheumatology and Internal Medicine, Medical University of Białystok (MUB), Department of Clinical and Experimental Medicine, University of Naples Federico II = Università degli studi di Napoli Federico II, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Department of Immunology and Rheumatology, University of Pecs, Institute of Rheumatology, University of Belgrade [Belgrade], Kos Genetic SRL, Institute of Genetic Epidemiology, Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Division of Rheumatology, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Centre d'Investigation Clinique [Grenoble] (CIC Grenoble), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], This project was funded by Agence Nationale pour la Recherche (Project ANR-08-GENO-016-1) and supported by research grants from SERVIER research group, SANOFI-AVENTIS, Association des Sclérodermies de France, and Groupe Français de Recherche sur la Sclérodermie. The KORA (Cooperative health research in the Region of Augsburg) studies were financed by the Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants from the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Part of this work was financed by the German National Genome Research Network (NGFN). This research was supported within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. HYPERGENES (European Network for Genetic-Epidemiological Studies) is funded by EU within the FP7: HEALTH-F4-2007-201550., European Project: 201550,EC:FP7:HEALTH,FP7-HEALTH-2007-A,HYPERGENES(2008), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Division of Rheumatology AOUC - Denothe Centre-Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Freiburg University Medical Center, German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Service de médecine interne [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), University of Verona (UNIVR), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical University of Bialystok, University of Naples Federico II, German Research Center for Environmental Health, Justus-Liebig-Universität Gießen (JLU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-Division of Rheumatology AOUC - Denothe Centre, Allanore, Y, Saad, M, Dieudé, P, Avouac, J, Distler, Jh, Amouyel, P, MATUCCI CERINIC, M, Riemekasten, G, Airo, P, Melchers, I, Hachulla, E, Cusi, D, Wichmann, He, Wipff, J, Lambert, Jc, Hunzelmann, N, Tiev, K, Caramaschi, P, Diot, E, KOWAL BIELECKA, O, Valentini, Gabriele, Mouthon, L, Czirják, L, Damjanov, N, Salvi, E, Conti, C, Müller, M, MÜLLER LADNER, U, Riccieri, V, Ruiz, B, Cracowski, Jl, Letenneur, L, Dupuy, Am, Meyer, O, Kahan, A, Munnich, A, Boileau, C, Martinez, M., Autard, Delphine, European Network for Genetic-Epidemiological Studies: building a method to dissect complex genetic traits, using essential hypertension as a disease model - HYPERGENES - - EC:FP7:HEALTH2008-01-01 - 2011-12-31 - 201550 - VALID, and Service de médecine interne [CHU Saint-Antoine]
Subjects: Male, Cancer Research, Linkage disequilibrium, Epidemiology, systemic sclerosis, RHOB, Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, Linkage Disequilibrium, MESH: Scleroderma, Systemic, Scleroderma, Major Histocompatibility Complex, Disease Mapping, TNIP1 locus, 0302 clinical medicine, Germany, Genetics of the Immune System, HLA-DQ beta-Chains, MESH: Proteins, Connective Tissue Diseases, rhoB GTP-Binding Protein, Genetics (clinical), Genetics, 0303 health sciences, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, MESH: Case-Control Studies, 3. Good health, DNA-Binding Proteins, Europe, Italy, MESH: Linkage Disequilibrium, Genetic Epidemiology, Medicine, Cytokines, Female, Inflammatory and Psoriatic Arthritis, France, Research Article, Adult, lcsh:QH426-470, Medizinische Fakultät -ohne weitere Spezifikation, Rheumatoid Arthritis, Single-nucleotide polymorphism, Locus (genetics), Biology, Systemic Lupus Erythematosus, Polymorphism, Single Nucleotide, Autoimmune Diseases, 03 medical and health sciences, MESH: Major Histocompatibility Complex, Rheumatology, RhoB GTP-Binding Protein, functional polymorphism, extracellular-matrix, association, scleroderma, population, disease, susceptibility, fibrosis, receptor, stat4, Psoriasis, Humans, SNP, Genetic Predisposition to Disease, genome-wide scan, ddc:610, Molecular Biology, MESH: Germany, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Genetic association, MESH: rhoB GTP-Binding Protein, 030203 arthritis & rheumatology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Scleroderma, Systemic, MESH: Humans, Proteins, MESH: Italy, MESH: Adult, MESH: HLA-DQ beta-Chains, MESH: Male, MESH: France, lcsh:Genetics, Immune System, Case-Control Studies, Immunology, MESH: Genome-Wide Association Study, Clinical Immunology, MESH: Europe, MESH: Female, MESH: DNA-Binding Proteins, Genome-Wide Association Study
Abstract: Systemic sclerosis (SSc) is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France, Italy, Germany, and Northern Europe. The initial genome-wide scan was conducted in a French post quality-control sample of 564 cases and 1,776 controls, using almost 500 K SNPs. Two SNPs from the MHC region, together with the 6 loci outside MHC having at least one SNP with a P, Author Summary Systemic sclerosis (SSc) is a connective tissue disease characterized by generalized microangiopathy, severe immunologic alterations, and massive deposits of matrix components in the connective tissue. Epidemiological investigations indicate that SSc follows a pattern of multifactorial inheritance; however, only a few loci have been replicated in multiple studies. We undertook a two-stage genome-wide association study of SSc involving over 8,800 individuals of European ancestry. Combined analyses showed independent association at the known HLA-DQB1 region and revealed associations at PSORS1C1, TNIP1, and RHOB loci, in agreement with a strong immune genetic component. Because of its biological relevance, and previous reports of genetic association at this locus with other connective tissue disorders, we investigated TNIP1 expression. We observed a markedly reduced expression of the gene and its protein product in SSc, as well as its potential implication in control of extra-cellular matrix synthesis, providing a new clue for a link between inflammation/immunity and fibrosis.
Published: 2011

36. EUSTAR biobanking: recommendations for the collection, storage and distribution of biospecimens in scleroderma research

Author: Kim Fligelstone, Gabriele Valentini, Marco Martucci-Cerinic, Nemanja Damjanov, Jacob M van Laar, Francesco Del Galdo, Serena Vettori, Ulrich A. Walker, Martin Aringer, Jérôme Avouac, László Czirják, Ingo H. Tarner, Christian Beyer, Yannick Allanore, Oliver Distler, Ulf Müller-Ladner, Ann Tyrrell Kennedy, Maurizio Cutolo, Christopher P. Denton, Jörg H W Distler, Serena Guiducci, Gabriela Riemekasten, Otylia Kowal-Bielecka, Alan Tyndall, University of Zurich, Distler, O, Beyer, C, Distler, Jh, Allanore, Y, Aringer, M, Avouac, J, Czirják, L, Cutolo, M, Damjanov, N, DEL GALDO, F, Fligelstone, K, Guiducci, S, KOWAL BIELECKA, O, VAN LAAR, Jm, MARTUCCI CERINIC, M, MÜLLER LADNER, U, Riemekasten, G, Tarner, Ih, Tyndall, A, Kennedy, At, Valentini, Gabriele, Vettori, Serena, Walker, Ua, Denton, C, and EUSTAR BIOBANKING, Group
Subjects: Pathology, medicine.medical_specialty, Safety Management, Quality Assurance, Health Care, 2745 Rheumatology, Immunology, 610 Medicine & health, Transportation, Tissue Banks, General Biochemistry, Genetics and Molecular Biology, Executive committee, Specimen Handling, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Clinical Protocols, Medizinische Fakultät, 1300 General Biochemistry, Genetics and Molecular Biology, medicine, Immunology and Allergy, Humans, ddc:610, skin and connective tissue diseases, Intensive care medicine, 030304 developmental biology, 030203 arthritis & rheumatology, 0303 health sciences, 2403 Immunology, Scleroderma, Systemic, integumentary system, business.industry, Online database, 10051 Rheumatology Clinic and Institute of Physical Medicine, Biobank, 3. Good health, 10076 Center for Integrative Human Physiology, 2723 Immunology and Allergy, 570 Life sciences, biology, Tissue Preservation, business
Abstract: The European League Against Rheumatism Scleroderma Trials and Research Group (EUSTAR) has established an online database with clinical data of currently more than 8200 patients with systemic sclerosis (SSc). In addition to clinical research, EUSTAR fosters biomolecular studies to develop novel biomarkers and therapies for SSc. High-quality biospecimens are the basis for successful biomolecular studies. The EUSTAR biobanking group has therefore developed recommendations to standardise the collection, storage and distribution of SSc biospecimens at EUSTAR centres. These recommendations consider the scientific challenges associated with biomolecular research in SSc and the organisational requirements of EUSTAR. They were approved by the EUSTAR executive committee as well as the EUSTAR board. Once they become effective, these recommendations will be the basis for international EUSTAR studies with large numbers of SSc biospecimens. These recommendations might also be followed by other SSc consortia to enable exchange of biosamples between different SSc initiatives and might serve as a template for biobanking initiatives in other rheumatic diseases.
Published: 2011

37. Association of the CD226 Ser(307) Variant With Systemic Sclerosis Evidence of a Contribution of Costimulation Pathways in Systemic Sclerosis Pathogenesis

Author: Philippe Dieudé, J. Cabane, J.L. Cracowski, Gabriele Valentini, G. Riemekasten, Catherine Boileau, Olivier Meyer, Marie-Elise Truchetet, Lucile Revillod, Zahir Amoura, Eric Hachulla, J. H. W. Distler, Yannick Allanore, Patrick H. Carpentier, P. Camaraschi, Luc Mouthon, Nicolas Hunzelmann, Mickaël Guedj, Inga Melchers, Marco Matucci-Cerinic, André Kahan, Nicolò Costantino Brembilla, Ingo H. Tarner, Carlo Chizzolini, Camille Francès, Valeria Riccieri, Julien Wipff, E. Diot, Paolo Airò, Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Université de Genève (UNIGE), Hôpitaux Universitaires de Genève (HUG), Université Paris Descartes - Paris 5 (UPD5), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University of Freiburg [Freiburg], Université de Lille, Droit et Santé, Hôpital Claude Huriez [Lille], CHU Lille, Spedali Civili, Centre Hospitalier Universitaire (CHU), University Hospital of Cologne, Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Grenoble, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Cardio-Thoracic and Respiratory Science, Second University of Naples, Naples, Italy, University of Verona (UNIVR), Justus-Liebig-Universität Gießen (JLU), Max Planck Institute of Molecular Plant Physiology (MPI-MP), Max-Planck-Gesellschaft, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Agence Nationale de la Recherche [R070994KS], Societe Francaise de Rhumatologie, Association des Sclerodermiques de France, Groupe Francais de Recherche sur la Sclerodermie, INSERM, Swiss National Science Foundation [31003A_124941/1], German Federal Ministry for Education and Research [01 GM 0310, 01 GM 0634], Actelion, Pfizer, Lilly, GlaxoSmithKline, Université de Genève = University of Geneva (UNIGE), Università degli Studi di Firenze = University of Florence (UniFI), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli studi di Verona = University of Verona (UNIVR), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Dieudé, P, Guedj, M, Truchetet, Me, Wipff, J, Revillod, L, Riemekasten, G, MATUCCI CERINIC, M, Melchers, I, Hachulla, E, Airo, P, Diot, E, Hunzelmann, N, Mouthon, L, Cabane, J, Cracowski, Jl, Riccieri, V, Distler, J, Amoura, Z, Valentini, Gabriele, Camaraschi, P, Tarner, I, Frances, C, Carpentier, P, Brembilla, Nc, Meyer, O, Kahan, A, Chizzolini, C, Boileau, C, and Allanore, Y.
Subjects: Nonsynonymous substitution, Antigens, Differentiation, T-Lymphocyte, Male, Systemic disease, CD226, T-Lymphocytes, Scleroderma, Systemic/ethnology/genetics/pathology, SUSCEPTIBILITY, medicine.disease_cause, Antigens, Differentiation, T-Lymphocyte/genetics, T-Lymphocytes/pathology, Autoimmunity, Pathogenesis, 0302 clinical medicine, Risk Factors, Immunopathology, Germany, IRF5, SCLERODERMA, Immunology and Allergy, FIBROSIS, Pharmacology (medical), European Continental Ancestry Group/genetics, [MATH]Mathematics [math], Polymorphism, Genetic/genetics, ADHESION MOLECULE, ddc:616, 0303 health sciences, Genetic Predisposition to Disease/genetics, Middle Aged, Connective tissue disease, 3. Good health, Italy, Female, France, Adult, EXPRESSION, GENETIC RISK-FACTOR, Genotype, Immunology, White People, 03 medical and health sciences, Rheumatology, medicine, Humans, Genetic Predisposition to Disease, [INFO]Computer Science [cs], 030304 developmental biology, Aged, 030203 arthritis & rheumatology, Autoimmune disease, Polymorphism, Genetic, Scleroderma, Systemic, KILLER T-CELLS, business.industry, DNAM-1, medicine.disease, POLYMORPHISM, Case-Control Studies, business
Abstract: International audience; Objective. The nonsynonymous polymorphism rs763361 of the CD226 gene, which encodes DNAX accessory molecule 1, which is involved in T cell co-stimulation pathways, has recently been identified as a genetic risk factor for autoimmunity. The purpose of this study was to test for association of the CD226 rs763361 polymorphism with systemic sclerosis (SSc) in European Caucasian populations. Methods. CD226 rs763361 was genotyped in 3,632 individuals, consisting of a discovery sample (991 SSc patients and 1,008 controls) and a replication sample (999 SSc patients and 634 controls). All study subjects were of European Caucasian origin. Expression of CD226 was assessed on peripheral blood mononuclear cells obtained from 21 healthy donors genotyped for CD226 rs763361. Results. The CD226 rs763361 T allele was found to be associated with SSc in both the discovery and the replication samples, showing the following results in the combined populations: odds ratio (OR) 1.22 (95% confidence interval [95% CI] 1.10-1.34), P = 5.69 x 10(-5). The CD226 T allele was also associated with various SSc subsets, highlighting a potential contribution to disease severity. The most remarkable associations of the CD226 TT risk genotype were observed with the diffuse cutaneous SSc subtype, the anti-topoisomerase I antibody-positive, and SSc-related fibrosing alveolitis subsets: OR 1.86 (95% CI 1.42-2.43), P = 5.15 x 10(-6), OR 1.82 (95% CI 1.38-2.40), P = 2.16 x 10(-5), and OR 1.61 (95% CI 1.25-2.08), P = 2.73 x 10(-4), respectively. CD226 expression was not significantly influenced by CD226 rs763361 genotypes whatever the T cell subtype investigated. Conclusion. Our results establish CD226 as a new SSc genetic susceptibility factor underlying the contribution of costimulation pathways in the pathogenesis of SSc. Further work is nevertheless needed to define the causal variant at the CD226 locus as well as the functional consequences.
Published: 2011

38. Clinical prediction of 5-year survival in systemic sclerosis: validation of a simple prognostic model in EUSTAR centres

Author: Jaap Fransen, Roger Hesselstrand, Marco Matucci-Cerinic, Roberto Giacomelli, Madelon C. Vonk, Alexandra Balbir-Gurman, L. Beretta, Yannick Allanore, Patricia Carreira, N. Hunzelmann, Dominique Farge, Stanisław Sierakowski, Gabriele Valentini, Gabriela Riemekasten, P. Airo, L. Czirják, Armando Gabrielli, Murat Inanc, Susanne Ullman, Valeria Riccieri, D. Popa-Diaconu, F.H.J. van den Hoogen, Fransen, J, POPA DIACONU, D, Hesselstrand, R, Carreira, P, Valentini, Gabriele, Beretta, L, Airo, P, Inanc, M, Ullman, S, BALBIR GURMAN, A, Sierakowski, S, Allanore, Y, Czirjak, L, Riccieri, V, Giacomelli, R, Gabrielli, A, Riemekasten, G, MATUCCI CERINIC, M, Farge, D, Hunzelmann, N, VAN DEN HOOGEN, Fh, and Vonk, Mc
Subjects: Adult, Male, medicine.medical_specialty, Immunology, Blood Sedimentation, General Biochemistry, Genetics and Molecular Biology, Sex Factors, Rheumatology, DLCO, Internal medicine, medicine, Humans, Immunology and Allergy, Risk factor, Aged, Scleroderma, Systemic, medicine.diagnostic_test, Receiver operating characteristic, business.industry, Age Factors, Middle Aged, Prognosis, medicine.disease, Connective tissue disease, Surgery, Europe, Proteinuria, Erythrocyte sedimentation rate, Cohort, Prognostic model, Pulmonary Diffusing Capacity, Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2], Female, Epidemiologic Methods, business
Abstract: ObjectiveSystemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accurate in other patients, especially from other centres or countries. A study was undertaken to validate the prognostic model to predict 5-year survival in SSc in other centres throughout Europe.MethodsA European multicentre cohort of patients with SSc diagnosed before 2002 was established. Patients with SSc according to the preliminary American College of Rheumatology classification criteria were eligible for the study when they were followed for at least 5 years or shorter if they died. The primary outcome was 5-year survival after diagnosis of SSc. The predefined prognostic model uses the following baseline variables: age, gender, presence of urine protein, erythrocyte sedimentation rate (ESR) and carbon monoxide diffusing capacity (DLCO).ResultsData were available for 1049 patients, 119 (11%) of whom died within 5 years after diagnosis. Of the patients, 85% were female, the mean (SD) age at diagnosis was 50 (14) years and 30% were classified as having diffuse cutaneous SSc. The prognostic model with age (OR 1.03), male gender (OR 1.93), urine protein (OR 2.29), elevated ESR (1.89) and low DLCO (OR 1.94) had an area under the receiver operating characteristic curve of 0.78. Death occurred in 12 (2.2%) of 509 patients with no risk factors, 45 (13%) of 349 patients with one risk factor, 55 (33%) of 168 patients with two risk factors and 7 (30%) of 23 patients with three risk factors.ConclusionA simple prognostic model using three disease factors to predict 5-year survival at diagnosis in SSc showed reasonable performance upon validation in a European multicentre study.
Published: 2011

39. Association of a KCNA5 gene polymorphism with systemic sclerosis-associated pulmonary arterial hypertension in the European Caucasian population

Author: J.L. Cracowski, Julien Wipff, Eric Hachulla, Philippe Dieudé, Paolo Airò, Patrick H. Carpentier, Kiet Tiev, E. Diot, Yannick Allanore, Gabriele Valentini, Barbara Ruiz, Catherine Boileau, Paola Caramaschi, Barbara Girerd, Bruno Degano, Marc Humbert, Marco Matucci-Cerinic, Olivier Meyer, Jérôme Avouac, G. Riemekasten, Inga Melchers, Jean Sibilia, Zahir Amoura, J. H. W. Distler, Valeria Riccieri, Mickaël Guedj, André Kahan, Luc Mouthon, Nicolas Hunzelmann, Ingo H. Tarner, Wipff, J, Dieudé, P, Guedj, M, Ruiz, B, Riemekasten, G, Cracowski, Jl, MATUCCI CERINIC, M, Melchers, I, Humbert, M, Hachulla, E, Airo, P, Diot, E, Hunzelmann, N, Caramaschi, P, Sibilia, J, Valentini, Gabriele, Tiev, K, Girerd, B, Mouthon, L, Riccieri, V, Carpentier, Ph, Distler, J, Amoura, Z, Tarner, I, Degano, B, Avouac, J, Meyer, O, Kahan, A, Boileau, C, Allanore, Y., Association des Sclerodermiques de France, INSERM, Agence Nationale pour la Recherche [R07094KS], Societe Francaise de Rhumatologie, Groupe Francais de Recherche sur la Sclerodermie, and German Federal Ministry for Education and Research [01 GM 0310, 01 GM 0634]
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Candidate gene, STRATEGIES, SMOOTH-MUSCLE-CELLS, [SDV]Life Sciences [q-bio], Hypertension, Pulmonary, Immunology, Population, Single-nucleotide polymorphism, SUSCEPTIBILITY, Gastroenterology, Polymorphism, Single Nucleotide, CLASSIFICATION, White People, CAPACITY, Kv1.5 Potassium Channel, Rheumatology, RISK-FACTOR, IRF5, SCLERODERMA, Internal medicine, medicine, Odds Ratio, Immunology and Allergy, Humans, Pharmacology (medical), Genetic Predisposition to Disease, PREDICTORS, skin and connective tissue diseases, education, Allele frequency, Associated Pulmonary Arterial Hypertension, Aged, education.field_of_study, Scleroderma, Systemic, integumentary system, MUTATIONS, business.industry, Case-control study, Odds ratio, Middle Aged, Europe, Case-Control Studies, Female, Gene polymorphism, business
Abstract: Objective Pulmonary arterial hypertension (PAH) has emerged as a leading cause of death in systemic sclerosis (SSc). The genetic basis of PAH has been unraveled in recent years, with a major role played by transforming growth factor β receptors; however, some other candidate genes have also been advocated, including potassium voltage-gated channel, shaker-related subfamily, member 5 (KCNA5). We undertook this study to determine whether KCNA5 polymorphisms confer susceptibility to SSc and its vascular phenotype, including PAH. Methods Four KCNA5 single-nucleotide polymorphisms (SNPs), rs10744676, rs1860420, rs3741930, and rs2284136, were genotyped in a discovery set of 638 SSc patients and 469 controls. In addition, rs10744676 was genotyped in an independent replication sample (938 SSc patients and 564 controls) and in a cohort of 168 patients with different PAH subtypes. Results The KCNA5 rs10744676 variant was found to be associated with SSc in the discovery sample, with an odds ratio (OR) of 0.62 (95% confidence interval [95% CI] 0.48–0.79, adjusted P = 0.0003) in comparison with controls (C allele frequency 11.4% versus 17.2%). When subphenotypes were investigated, an association was found solely for PAH associated with SSc (OR 0.31 [95% CI 0.13–0.71], adjusted P = 0.04). The other KCNA5 SNPs tested were not associated with any SSc subset. The above association with PAH associated with SSc was replicated in the second set. In the combined population, rs10744676 was strongly associated with PAH associated with SSc in comparison with controls (OR 0.36 [95% CI 0.21–0.63], P = 0.0002). In the independent cohort of patients with PAH, after investigating PAH subtypes, only rs10744676 showed an association with PAH associated with SSc. Conclusion Our results provide the first evidence for an association between the KCNA5 rs10744676 variant and PAH associated with SSc.
Published: 2010

40. FRI0446 Severe Heart Disease in Systemic Sclerosis: Prevalence, Risk Factors and Current Treatment. A Eustar-Desscipher Study

Author: Ingo H. Tarner, Serena Vettori, Ulrich A. Walker, Ulf Mueller-Ladner, Suzana Jordan, L. Czirják, Marc Frerix, Veronika Lóránd, Elise Siegert, Marco Matucci-Cerinic, Yannick Allanore, Gabriele Valentini, F. Del Galdo, Christopher P. Denton, Giovanna Cuomo, G. Riemekasten, Oliver Distler, Veronika K. Jaeger, Vettori, Serena, Cuomo, Giovanna, Jaeger, V. K., Frerix, M., Siegert, E., Lorand, V., Jordan, S., Riemekasten, G., Allanore, Y., Czirjak, L., Tarner, I. H., Distler, O., Denton, C. P., Matucci Cerinic, M., Del Galdo, F., Walker, U. A., Mueller Ladner, U., and Valentini, G.
Subjects: medicine.medical_specialty, Univariate analysis, Myocarditis, Heart disease, business.industry, Immunology, Disease, medicine.disease, Sudden death, General Biochemistry, Genetics and Molecular Biology, Surgery, Rheumatology, Internal medicine, Heart failure, medicine, Immunology and Allergy, business, Rheumatism, Cause of death
Abstract: Background Heart disease in patients with systemic sclerosis (SSc) can cause manifestations such as cardiac blocks (CBs), ventricular arrhythmias (VA), and congestive heart failure (CHF) which may require a pacemaker/defibrillator implant, are the cause of death or sudden death (SD) in about 20% of patients and can be referred to as severe heart disease (SHD). The European League against Rheumatism – Scleroderma Trial and Research (EUSTAR) database provides an unique opportunity to address this topic. The results of such analysis are instrumental for the DeSScipher project, an EU funded project devoted to decipher the optimal management of SSc . Objectives To investigate the prevalence of each SHD manifestation and their associations with demographic, serological, clinical and therapeutic aspects in a large series of adult SSc patients. Methods Seven EUSTAR-DeSScipher centers provided clinical charts at study entry including all the items of SHD. The prevalence of any and each SHD manifestation was calculated. The associations with demographic, serological, clinical features and treatment with vasodilators, i.e. calcium channel blockers (CCBs) and /or ACE inhibitors (ACEi), were investigated by univariate analysis and confirmed by multivariate logistic regression analysis. Results At July 6th 2012, 1119 SSc patients from the 7 EUSTAR centers had no missing data (995 females, 164 males; median age 53.6 years, range 14-86). Out of them, 211 patients (19%) had at least 1 SHD manifestation, 152 patients had CBs (14%), 71 had VA (6%), 132 had CHF (12%), and 27 received a pacemaker/defibrillator implant (2%). CBs were the only SHD manifestation in 100 patients, VA in 31, and CHF in 80. No association was found between SHD and clinical (diffuse or limited) and serological (ACA or anti-Scl-70) subset. No association was found between either CHF or pacemaker/defibrillator implant and any other disease feature. In multiple logistic regression analysis, CBs were associated with bibasilar lung fibrosis at chest X-Ray (OR=2.6; 95%CI=1-6.4; p=0.04), while VA were associated with increased CPK levels (OR=11; 95%CI=1-117; p=0.02) and, unexpectedly, current CCB use (OR 10; 95%CI 1.4-76.1; p=0.02). Conclusions This is the first study devoted to investigate SHD in a large series of carefully assessed SSc patients. SHD was detected in about 19% of the cases, CBs in 14%, VA in 6%, CHF in 12%. Pacemaker/defibrillator implant was needed in 2.4%. These data highlight the importance of an accurate heart assessment in SSc patients. Moreover, the associations between VA and CPK elevation and current CCB use should stimulate the clinician to avoid these drugs in patients with myositis/myocarditis. Acknowledgements The DeSScipher project was funded by the European Community9s Framework Programme 7 (FP7-HEALTH-2012.2.4.4-2 - Observational trials in rare diseases) under grant agreement N° 305495 Disclosure of Interest S. Vettori Grant/research support from: Roche, Consultant for: Phadia Thermofisher, Pfizer, Abbvie, G. Cuomo: None declared, V. Jaeger: None declared, M. Frerix: None declared, E. Siegert: None declared, V. Lorand: None declared, S. Jordan: None declared, G. Riemekasten: None declared, Y. Allanore: None declared, L. Czirjak: None declared, I. Tarner: None declared, O. Distler Grant/research support from: 4D Science, Actelion, Active Biotec, Bayer-Schering, Biogen, Biovitrium, BMS, Boehringer Ingelheim Pharma, EpiPharm, Ergonex, GSK, Inventiva, Medac, Novartis, Pfizer, Pharmacyclics, Roche/Genentech, Sanofi/Genzyme, Serodapharm, Sinoxa and United BioSource Corporation, Consultant for: 4D Science, Actelion, Active Biotec, Bayer-Schering, Biogen, Biovitrium, BMS, Boehringer Ingelheim Pharma, EpiPharm, Ergonex, GSK, Inventiva, Medac, Novartis, Pfizer, Pharmacyclics, Roche/Genentech, Sanofi/Genzyme, Serodapharm, Sinoxa and United BioSource Corporation, C. Denton: None declared, M. Matucci-Cerinic: None declared, F. Del Galdo: None declared, U. Walker: None declared, U. Mueller-Ladner: None declared, G. Valentini: None declared
Published: 2015

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