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1. Variability of Primary Sjögren's Syndrome Is Driven by Interferon α and Interferon α Blood Levels Are Associated With the Class II HLA–DQ Locus

Author

Trutschel, Diana, Bost, Pierre, Mariette, Xavier, Bondet, Vincent, Llibre, Alba, Posseme, Celine, Charbit, Bruno, Thorball, Christian W., Jonsson, Roland, Lessard, Christopher J., Felten, Renaud, Ng, Wan Fai, Chatenoud, Lucienne, Dumortier, Hélène, Sibilia, Jean, Fellay, Jacques, Brokstad, Karl A., Appel, Silke, Tarn, Jessica R., Quintana‐Murci, Lluis, Mingueneau, Michael, Meyer, Nicolas, Duffy, Darragh, Schwikowski, Benno, Gottenberg, Jacques Eric, Dernis, Emmanuelle, Devauchelle‐Pensec, Valerie, Dieude, Philippe, Dubost, Jean‐Jacques, Fauchais, Anne‐Laure, Goeb, Vincent, Hachulla, Eric, Hatron, Pierre Yves, Larroche, Claire, Le Guern, Véronique, Morel, Jacques, Perdriger, Aleth, Salliot, Carinne, Rist, Stephanie, Saraux, Alain, Vittecoq, Olivier, Nocturne, Gaétane, Ravaud, Philippe, Seror, Raphaèle, Abel, Laurent, Alcover, Andres, Aschard, Hugues, Astrom, Kalla, Bousso, Philippe, Bruhns, Pierre, Cumano, Ana, Demangel, Caroline, Deriano, Ludovic, Di Santo, James, Dromer, Françoise, Eberl, Gérard, Enninga, Jost, Gelpi, Odile, GompertsBoneca, Ivo, Hasan, Milena, Hercberg, Serge, Lantz, Olivier, Leclerc, Claude, Mouquet, Hugo, Pellegrini, Sandra, Pol, Stanislas, Rausell, Antonio, Rogge, Lars, Sakuntabhai, Anavaj, Schwartz, Olivier, Shorte, Spencer, Soumelis, Vassili, Tangy, Frédéric, Tartour, Eric, Toubert, Antoine, Touvier, Mathilde, Ungeheuer, Marie‐Noëlle, Albert, Matthew L., Biomédecine computationelle des systèmes / Computational systems biomedicine, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Universität Zürich [Zürich] = University of Zurich (UZH), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Projet NECESSITY (PN), Hôpitaux Universitaires Paris Sud [AP-HP] (HUPS)-Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Immunologie Translationnelle - Translational Immunology lab, Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Ecole Polytechnique Fédérale de Lausanne (EPFL), Université de Lausanne = University of Lausanne (UNIL), Lausanne University Hospital, University of Bergen (UiB), Oklahoma Medical Research Foundation (OMRF), University of Oklahoma Health Sciences Center (OUHSC), Université de Strasbourg (UNISTRA), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Newcastle University [Newcastle], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Immunologie, Immunopathologie et Chimie Thérapeutique (I2CT), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Biogen Inc. [Cambridge, MA, USA], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Supported by the Innovative Medicines Initiative 2 Joint Undertaking (JU) (grant 806975). The JU receives support from the European Union’s Horizon 2020 research and innovation program and the European Unionand the European Federation of Pharmaceutical Industries and Associations. This work was also supported by the National Institutes of Health (National Institute of Arthritis and Musculoskeletal Skin Disease grant R01-AR-065953). The Assessment of Systemic Signs and Evolution in Sjögren’s Syndrome(ASSESS) national multicenter prospective cohort was formed in 2006 with aFrench Ministry of Health grant (Programme Hospitalier de Recherche Clinique 2005 P060228). The ASSESS cohort is promoted by the French Society of Rheumatology and receives research grants from the French Society of Rheumatology. Dr. Gottenberg’s work was supported by Bristol Myers Squibbfor transcriptomic analysis of the ASSESS and Norwegian cohorts and by Geneviève Garnier (Association Française du Syndrome de Gougerot-Sjögrenet des syndromes secs). Drs. Trutschel’s and Schwikowski’s work was supported by Geneviève Garnier (Association Française du Syndrome de Gougerot-Sjögren et des syndromes secs)., Milieu Intérieur Consortium, ASSESS study investigators, and NECESSITY Consortium: Emmanuelle Dernis, Valerie Devauchelle-Pensec, Philippe Dieude, Jean-Jacques Dubost, Anne-Laure Fauchais, Vincent Goeb, Eric Hachulla, Pierre Yves Hatron, Claire Larroche, Véronique Le Guern, Jacques Morel, Aleth Perdriger, Carinne Salliot, Stephanie Rist, Alain Saraux, Jean Sibilia, Olivier Vittecoq, Gaétane Nocturne, Philippe Ravaud, Raphaèle Seror, Laurent Abel, Andres Alcover, Hugues Aschard, Kalla Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Odile Gelpi, Ivo GompertsBoneca, Milena Hasan, Serge Hercberg, Olivier Lantz, Claude Leclerc, Hugo Mouquet, Sandra Pellegrini, Stanislas Pol, Antonio Rausell, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Vassili Soumelis, Frédéric Tangy, Eric Tartour, Antoine Toubert, Mathilde Touvier, Marie-Noëlle Ungeheuer, Matthew L Albert, Darragh Duffy, Lluis Quintana-Murci., European Project: 806975,NECESSITY, Clauss, Isabelle, and NEw Clinical Endpoints in primary Sjögren’s Syndrome: an Interventional Trial based on stratifYing patients - NECESSITY - 0000-00-00 - 0000-00-00 - 806975 - VALID

Subjects
Proteomics, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Sjogren's Syndrome, Rheumatology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, HLA-DQ Antigens, Immunology, Humans, Interferon-alpha, Immunology and Allergy, Prospective Studies
Abstract

Objective: Primary Sjögren's syndrome (SS) is the second most frequent systemic autoimmune disease, affecting 0.1% of the general population. To characterize the molecular and clinical variabilities among patients with primary SS, we integrated transcriptomic, proteomic, cellular, and genetic data with clinical phenotypes in a cohort of 351 patients with primary SS. Methods: We analyzed blood transcriptomes and genotypes of 351 patients with primary SS who were participants in a multicenter prospective clinical cohort. We replicated the transcriptome analysis in 3 independent cohorts (n = 462 patients). We determined circulating interferon-α (IFNα) and IFNγ protein concentrations using digital single molecular arrays (Simoa). Results: Transcriptome analysis of the prospective cohort showed a strong IFN gene signature in more than half of the patients; this finding was replicated in the 3 independent cohorts. Because gene expression analysis did not discriminate between type I IFN and type II IFN, we used Simoa to demonstrate that the IFN transcriptomic signature was driven by circulating IFNα and not by IFNγ protein levels. IFNα protein levels, detectable in 75% of patients, were significantly associated with clinical and immunologic features of primary SS disease activity at enrollment and with increased frequency of systemic complications over the 5-year follow-up. Genetic analysis revealed a significant association between IFNα protein levels, a major histocompatibility (MHC) class II haplotype, and anti-SSA antibody. Additional cellular analysis revealed that an MHC class II HLA–DQ locus acts through up-regulation of HLA class II molecules on conventional dendritic cells. Conclusion: We identified the predominance of IFNα as a driver of primary SS variability, with IFNα demonstrating an association with HLA gene polymorphisms., Arthritis & Rheumatology, 74 (12), ISSN:2326-5191, ISSN:2326-5205

Published
2022
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2. Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry

Author

Sparks, Jeffrey A, Wallace, Zachary S, Seet, Andrea M, Gianfrancesco, Milena A, Izadi, Zara, Hyrich, Kimme L, Strangfeld, Anja, Gossec, Laure, Carmona, Loreto, Mateus, Elsa F, Lawson-Tovey, Saskia, Trupin, Laura, Rush, Stephanie, Katz, Patricia, Schmajuk, Gabriela, Jacobsohn, Lindsay, Wise, Leanna, Gilbert, Emily L, Duarte-García, Ali, Valenzuela-Almada, Maria O, Pons-Estel, Guillermo J, Isnardi, Carolina A, Berbotto, Guillermo A, Hsu, Tiffany Y-T, D'Silva, Kristin M, Patel, Naomi J, Kearsley-Fleet, Lianne, Schäfer, Martin, Ribeiro, Sandra Lúcia Euzébio, Al Emadi, Samar, Tidblad, Liselotte, Scirè, Carlo Alberto, Raffeiner, Bernd, Thomas, Thierry, Flipo, René-Marc, Avouac, Jérôme, Seror, Raphaèle, Bernardes, Miguel, Cunha, Maria Margarida, Hasseli, Rebecca, Schulze-Koops, Hendrik, Müller-Ladner, Ulf, Specker, Christof, Souza, Viviane Angelina de, Mota, Licia Maria Henrique da, Gomides, Ana Paula Monteiro, Dieudé, Philippe, Nikiphorou, Elena, Kronzer, Vanessa L, Singh, Namrata, Ugarte-Gil, Manuel F, Wallace, Beth, Akpabio, Akpabio, Thomas, Ranjeny, Bhana, Suleman, Costello, Wendy, Grainger, Rebecca, Hausmann, Jonathan S, Liew, Jean W, Sirotich, Emily, Sufka, Paul, Robinson, Philip C, Machado, Pedro M, Yazdany, Jinoos, and COVID-19 Global Rheumatology Alliance

Subjects
Male, rheumatoid arthritis, abatacept, SARS-CoV-2, Arthritis, Inflammatory and immune system, Clinical Sciences, Immunology, tumour necrosis factor inhibitors, COVID-19, Middle Aged, Severity of Illness Index, Autoimmune Disease, Arthritis & Rheumatology, rituximab, Good Health and Well Being, COVID-19 Global Rheumatology Alliance, Rheumatoid, Antirheumatic Agents, Public Health and Health Services, Humans, Female, Registries, Aged
Abstract

ObjectiveTo investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA).MethodsWe analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders.ResultsOf 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity.ConclusionsPeople with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.

Published
2021

3. Additional file 1 of Response to COVID-19 mRNA vaccination in multiple myeloma is conserved but impaired compared to controls

Author

Bitoun, Samuel, Henry, Julien, Vauloup-Fellous, Christelle, Dib, Nicolas, Belkhir, Rakiba, Mouna, Lina, Joly, Candie, Desjardins, Delphine, Bitu, Marie, Le Grand, Roger, Seror, Raphaèle, Roque Afonso, Anne-Marie, and Mariette, Xavier

Abstract

Additional file 1. Supplementary figure 1. Correlation between anti-Spike IgG (Elecsys Anti-SARS-CoV-2 S, Cobas, Roche Diagnostics; cut off: 0.4 IU/ml) and neutralizing activity of anti-SARS-CoV-2 antibodies (iFlash-2019-nCoV Nab assay, Ylho; cut-off: 24 IU/ml) of Multiple myeloma and control patients. The threshold of 50 IU/mL with the anti-Spike IgG assay represents the limit established on a separate cohort, above which 98% of sample tested have detectable neutralizing activity of anti- SARS-CoV-2 antibodies as defined by the threshold of 24 IU/ml with the neutralization assay. r = 0.69 p ≤ 0,0001 Spearman test.

Published
2021
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4. SARS-CoV-2 infection in patients with primary Sjögren syndrome: characterization and outcomes of 51 patients

Author

Brito-Zerón, Pilar, Melchor, Sheila, Seror, Raphaèle, Priori, Roberta, Solans, Roser, Kostov, Belchin, Baldini, Chiara, Carubbi, Francesco, Callejas, Jose Luis, Guisado-Vasco, Pablo, Hernández-Molina, Gabriela, Pasoto, Sandra G, Valim, Valeria, Sisó-Almirall, Antoni, Mariette, Xavier, Carreira, Patricia, Ramos-Casals, Manuel, Brito-Zerón, P, Morcillo, C, Flores-Chávez, A, Ramos-Casals, M, Acar-Denizli, N, Horvath, I F, Szanto, A, Tarr, T, Seror, R, Mariette, X, Mandl, T, Olsson, P, Li, X, Xu, B, Baldini, C, Bombardieri, S, Gottenberg, J E, Gandolfo, S, De Vita, S, Priori, R, Giardina, F, Hernandez-Molina, G, Sánchez-Guerrero, J, Kruize, A A, Hinrichs, A, Valim, V, Isenberg, D, Solans, R, Rischmueller, M, Downie-Doyle, S, Kwok, S-K, Park, S-H, Nordmark, G, Suzuki, Y, Kawano, M, Giacomelli, R, Devauchelle-Pensec, V, Saraux, A, Hofauer, B, Knopf, A, Bootsma, H, Vissink, A, Morel, J, Vollenveider, C, Atzeni, F, Retamozo, S, Moça Trevisano, V, Armagan, B, Kilic, L, Kalyoncu, U, Pasoto, S G, Kostov, B, Sisó-Almirall, A, Consani-Fernández, S, Carubbi, F, Callejas, J L, López-Dupla, M, Pérez-Alvarez, R, Akasbi, M, Guisado-Vasco, P, Sánchez, I, Hospital Universitario 12 de Octubre [Madrid], EULAR standing committee of People with Arthritis/Rheumatism in Europe (PARE), H. CIMA-Sanitas, Barcelona, CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona, Instituto Mexicano del Seguro Social [Mexico City, Mexico] (IMSS), Universidad de Colima [Mexico], Hospital Clinic [Barcelona, Spain], İstanbul Üniversitesi, İstanbul, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary, MTA-Debreceni Egyetem, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, Skåne University Hospital [Malmö, Suède], Stockholm University, Wuhan University [China], Pisa University Hospital, Nuclear Medicine Unit, Humanitas Gavazzeni, Bergamo, Italy, University Hospitals, Strasbourg, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Federal University of Espírito Santo, University Hospital Vall d’Hebròn [Barcelona, Spain], Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigaciones Biomèdiques August Pi i Sunye (IDIBAPS), Università degli studi di Palermo - University of Palermo, Hospitales Universitarios de Granada/Universidad de Granada, Hospital Universitario Quironsalud, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Rheumatology Unit, Department of Internal Medicine, University of Palermo, Palermo, Italy, and Michel, Geneviève

Subjects
Male, medicine.medical_specialty, Multivariate analysis, [SDV.IMM] Life Sciences [q-bio]/Immunology, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Comorbidity, Laboratory abnormality, comorbidities, outcomes, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Risk Factors, Internal medicine, medicine, Humans, In patient, Pharmacology (medical), 030212 general & internal medicine, Registries, Risk factor, Primary Sjögren Syndrome, AcademicSubjects/MED00360, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, business.industry, SARS-CoV-2, COVID-19, Primary SS, SARS-Cov-2, Middle Aged, medicine.disease, 3. Good health, Hospitalization, Sjogren's Syndrome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Original Article, Female, business
Abstract

Objective To analyse the prognosis and outcomes of SARS-CoV-2 infection in patients with primary SS. Methods We searched for patients with primary SS presenting with SARS-CoV-2 infection (defined following and according to the European Centre for Disease Prevention and Control guidelines) among those included in the Big Data Sjögren Registry, an international, multicentre registry of patients diagnosed according to the 2002/2016 classification criteria. Results A total of 51 patients were included in the study (46 women, mean age at diagnosis of infection of 60 years). According to the number of patients with primary SS evaluated in the Registry (n = 8211), the estimated frequency of SARS-CoV-2 infection was 0.62% (95% CI 0.44, 0.80). All but two presented with symptoms suggestive of COVID-19, including fever (82%), cough (57%), dyspnoea (39%), fatigue/myalgias (27%) and diarrhoea (24%), and the most frequent abnormalities included raised lactate dehydrogenase (LDH) (88%), CRP (81%) and D-dimer (82%) values, and lymphopenia (70%). Infection was managed at home in 26 (51%) cases and 25 (49%) required hospitalization (five required admission to ICU, four died). Compared with patients managed at home, those requiring hospitalization had higher odds of having lymphopenia as laboratory abnormality (adjusted OR 21.22, 95% CI 2.39, 524.09). Patients with comorbidities had an older age (adjusted OR 1.05, 95% CI 1.00, 1.11) and showed a risk for hospital admission six times higher than those without (adjusted OR 6.01, 95% CI 1.72, 23.51) in the multivariate analysis. Conclusion Baseline comorbidities were a key risk factor for a more complicated COVID-19 in patients with primary SS, with higher rates of hospitalization and poor outcomes in comparison with patients without comorbidities.

Published
2020
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5. Influence of epidemiology and ethnicity on systemic expression of primary Sjögren syndrome in 9974 patients

Author

Retamozo, Soledad, Acar-Denizli, Nihan, Fai Ng, W, Zeher, M, Rasmussen, A, Seror, Raphaèle, Li, X, Baldini, C, Gottenberg, Jacques-Eric, Danda, D, Quartuccio, Luca, Priori, R, Hernandez-Molina, G, Armagan, B, Kruize, Aike A, Kwok, S-K, Wahren-Herlenius, Marie, Praprotnik, Sonja, Sene, Damien, Bartoloni, Elena, Solans, R., Rischmueller, Maureen, Mandl, T, Suzuki, Y, Isenberg, David, Valim, V, Wiland, Piotr, Nordmark, Gunnel, Fraile, G, Bootsma, Hendrika, Nakamura, T, Giacomelli, R., Devauchelle-Pensec, Valérie, Hofauer, Benedikt, Bombardieri, Michele, Fernandes Moça Trevisani, Virginia, Hammenfors, D, S.G., Pasoto, Gheita, Tamer A, Atzeni, Fabiola, Morel, Jacques, Vollenveider, Cristina, Brito-Zerón, Pilar, Ramos-Casals, Manel, Rheumatology Unit, Cordoba (Institute University of Biomedical Sciences University of Cordoba (IUCBC), Hospital Clinic (IDIBAPS), INICSA, UNC, CONICED, Cordoba, Mimar Sinan Üniversitesi, Newcastle University [Newcastle], University of Debrecen [Hungary], Oklahoma Medical Research Foundation, Oklahoma Medical Research Foundation (OMRF), Université Paris Sud (Paris 11), Anhui Provincial Hosp, University of Pisa - Università di Pisa, Les Hôpitaux Universitaires de Strasbourg (HUS), Christian Medical College & Hospital, Rheumatology Clinic, Udine (DSMB), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], INCMNSS, Mexico, Hacettepe University = Hacettepe Üniversitesi, University Medical Center [Utrecht], Catholic University of Korea, Unit of Experimental Rheumatology, Stockhom (Department of Medicine), Department of Rheumatology, University Medical Centre, Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Perugia (UNIPG), Vall d'Hebron University Hospital [Barcelona], The University of Western Australia (UWA), Lund University, Malmö University Hospital, Kanazawa Medical University, Centre for Rheumatology - London, Federal University of Espírito Santo, Wroclaw Medical University, Uppsala Universitet [Uppsala], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Department of Rheumatology and Clinical Immunology Groningen (Dep Rheum - GRONINGEN), University Medical Center Groningen [Groningen] (UMCG), Nagasaki University, University of L'Aquila [Italy] (UNIVAQ), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Hals-Nasen-Ohrenklinik und Poliklinik, Munchen, Queen Mary University London, Université Fédérale de São Paulo (Unifesp), Haukeland University Hospital, University of Bergen (UiB), Hospital das Clinicas, University of Sao Paulo School of Medicine, Cairo University - Faculty of Medicine, Messina and Milan Univ, Milan, Service de Rhumatologie [CHU de Montpellier], CHU Montpellier, German Hosp, Buenos Aires, H. CIMA-Sanitas, Barcelona, and Michel, Geneviève

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

6. Sjögren big data project, the first example of data sharing in autoimmune diseases: analysis of 10475 worldwide patients

Author

Retamozo, Soledad, Acar-Denizli, Nihan, Fai Ng, W, Zeher, M, Rasmussen, A, Mandl, T, Seror, Raphaèle, Li, X, Baldini, C, Gottenberg, Jacques-Eric, Danda, D, Quartuccio, Luca, A, Minniti, Hernandez-Molina, Gabriela, Kalyoncu, Umut, Kruize, Aike A, Kwok, S-K, Wahren-Herlenius, Marie, Praprotnik, Sonja, Sene, Damien, Bartolini, E, Solans, R., Rischmueller, Maureen, Suzuki, Y, Isenberg, David, Valim, V, Wiland, Piotr, Nordmark, Gunnel, Fraile, G, Bootsma, Hendrika, Nakamura, T, Giacomelli, R., Devauchelle-Pensec, Valérie, Hofauer, Benedikt, Bombardieri, Michèle, Fernandes Moça Trevisani, Virginia, Hammenfors, D, S.G., Pasoto, Gheita, Tamer A, Atzeni, Fabiola, Morel, Jacques, Vollenveider, Cristina, Brito-Zerón, Pilar, Ramos-Casals, Manuel, Hospital Clinic (IDIBAPS), Rheumatology Unit, Cordoba (Institute University of Biomedical Sciences University of Cordoba (IUCBC), INICSA, UNC, CONICED, Cordoba, Mimar Sinan Üniversitesi, Newcastle University [Newcastle], University of Debrecen [Hungary], Oklahoma Medical Research Foundation, Oklahoma Medical Research Foundation (OMRF), Lund University, Malmö University Hospital, Université Paris Sud (Paris 11), Anhui Provincial Hosp, University of Pisa - Università di Pisa, Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Christian Medical College & Hospital, Rheumatology Clinic, Udine (DSMB), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Hacettepe University = Hacettepe Üniversitesi, University Medical Center [Utrecht], Catholic University of Korea, Unit of Experimental Rheumatology, Stockhom (Department of Medicine), Department of Rheumatology, University Medical Centre, Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université dePerugia, Vall d'Hebron University Hospital [Barcelona], The University of Western Australia (UWA), Kanazawa University (KU), Centre for Rheumatology - London, Federal University of Espírito Santo, Wroclaw Medical University, Department of Medical Sciences, Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Department of Rheumatology and Clinical Immunology Groningen (Dep Rheum - GRONINGEN), University Medical Center Groningen [Groningen] (UMCG), Nagasaki University, University of L'Aquila [Italy] (UNIVAQ), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Hals-Nasen-Ohrenklinik und Poliklinik, Munchen, The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London (QMUL), Université Fédérale de São Paulo (Unifesp), Haukeland University Hospital, University of Bergen (UiB), Hospital das Clinicas, University of Sao Paulo School of Medicine, Cairo University - Faculty of Medicine, Messina and Milan Univ, Milan, Service de Rhumatologie [CHU de Montpellier], CHU Montpellier, German Hosp, Buenos Aires, H. CIMA-Sanitas, Barcelona, CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona, and Michel, Geneviève

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

7. Is there a seasonal effect on fatigue, pain and dryness in primary Sjögren's syndrome? Data from the prospective assess cohort and from 3 randomized controlled trials

Author

Duret, Pierre-Marie, Meyer, Nicolas, Saraux, Alain, Devauchelle-Pensec, Valérie, Sibilia, Jean, Seror, Raphaèle, Le Guern, Veronique, Larroche, Claire, Perdriger, Aleth, Mariette, Xavier, Gottenberg, Jacques-Eric, Hôpital de Hautepierre [Strasbourg], CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Internal Medicine, Paris, Centre Hospitalier Universitaire [Rennes], Univ. Paris-Sud, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2017

8. Outcome measures for primary Sjogren's syndrome

Author

Seror, Raphaèle, Theander, Elke, Bootsma, Hendrika, Bowman, Simon J, Tzioufas, Athanasios, Gottenberg, Jacques-Eric, Ramos-Casals, Manel, Dörner, Thomas, Ravaud, Philippe, Mariette, Xavier, Vitali, Claudio, Saraux, Alain, Centre d'épidémiologie Clinique [Hôtel-Dieu], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu, Service de rhumatologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Rheumatology (Dep Rheumato - Malmo - SUEDE), Skåne University Hospital, Department of Rheumatology and Clinical Immunology Groningen (Dep Rheum - GRONINGEN), University Medical Center Groningen [Groningen] (UMCG), University Hospital Birmingham, Department of Pathophysiology, Medical School, University of Athens, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Autoimmune Diseases Josep Font Barcelona, CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona, Charité Hospital, Humboldt Universität zu Berlin, Sections of Rheumatology (Rheumatol - LECCO), Instituto San Giuseppe, Centre d'Investigation Clinique INSERM 1412 (CIC 1412 - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Humboldt-Universität zu Berlin, Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM)

Subjects
medicine.medical_specialty, Systemic disease, SYMPTOMS, MESH: Clinical Trials as Topic, MESH: Self Report, [SDV]Life Sciences [q-bio], ESSPRI, Immunology, Placebo-controlled study, Arthritis, Disease, PLACEBO-CONTROLLED TRIAL, Severity of Illness Index, Outcome measure, DOUBLE-BLIND, EUROPEAN LEAGUE, Internal medicine, MESH: Severity of Illness Index, Outcome Assessment, Health Care, medicine, Humans, Immunology and Allergy, SYSTEMIC-LUPUS-ERYTHEMATOSUS, Pathological, MESH: Outcome Assessment (Health Care), DISEASE-ACTIVITY INDEX, DRY MOUTH, Clinical Trials as Topic, MESH: Humans, business.industry, PATIENT-REPORTED INDEX, Reproducibility of Results, RITUXIMAB TREATMENT, medicine.disease, OPEN-LABEL, Clinical trial, MESH: Reproducibility of Results, Peripheral neuropathy, MESH: Sjogren's Syndrome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Sjogren's syndrome, Cohort, Physical therapy, Self Report, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, ESSDAI
Abstract

Lymphocytic infiltration of different exocrine and non-exocrine epithelia is the pathological hallmark of primary Sjogren's syndrome, whereas involvement of salivary and lachrymal glands with the clinical counterpart of dry eye and dry mouth are the predominant features of the disease, together with fatigue and musculoskeletal pain. In addition, systemic manifestations, like arthritis, skin vasculitis, peripheral neuropathy, glomerulonephritis, may also be present in a consistent number of patients. As result, clinical features in SS can be divided into two facets: the benign subjective but disabling manifestations such as dryness, pain and fatigue, and the systemic manifestations. In the past decades, great efforts have been made to develop valid tools for the assessment of these both facets. Disease specific questionnaires such as Profile of Fatigue and Discomfort (PROFAD) and Sicca Symptom Inventory (SSI) have been proposed for evaluation of patients' symptoms, whereas different composite indexes have been suggested for the assessment of systemic disease activity. After that, an international project supported by EULAR, emerged to develop consensus disease activity indexes: the EULAR Sjogren's Syndrome Patients Reported Index (ESSPRI), and the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI), a systemic activity index to assess systemic manifestations. Both EUIAR indexes have been developed in an international collaboration to be consensual. Both indices have now been validated in a large independent international cohort. They both have been shown to be feasible, valid and reliable instruments. Also, we have found that these two scores did not correlate, suggesting that these two indexes assess two different disease components that poorly overlap, but were complementary. The sensitivity to change of both scores has been assessed, they are both able to detect change, however, ESSDAI score, like other systemic score, is more sensitive to change than ESSPRI and other patient scores. Current work is ongoing to define disease activity levels and clinically important changes for defining significant clinical improvement with the systemic score ESSDAI, and ESSPRI. We hope that this increased knowledge on the way to assess patients with primary SS, along with the emergence of new targeted therapy, will put a great input in the improvement of conduction of clinical trials in pSS.. (C) 2013 Elsevier Ltd. All rights reserved.

Published
2014

9. Validation of EULAR primary Sjogren's syndrome disease activity (ESSDAI) and patient indexes (ESSPRI)

Author

Seror, Raphaèle, Theander, Elke, Brun, Johan G, Ramos-Casals, Manel, Valim, Valeria, Dörner, Thomas, Bootsma, Hendrika, Tzioufas, Athanasios, Solans-Laqué, Roser, Mandl, Thomas, Gottenberg, Jacques-Eric, Hachulla, Eric, Sivils, Kathy L, Ng, Wan-Fai, Fauchais, Anne-Laure, Bombardieri, Stefano, Valesini, Guido, Bartoloni, Elena, Saraux, Alain, Tomsic, Matija, Sumida, Takayuki, Nishiyama, Susumu, Caporali, Roberto, Kruize, Aike A, Vollenweider, Cristina, Ravaud, Philippe, Vitali, Claudio, Mariette, Xavier, Bowman, Simon J, EULAR Sjögren's Task Force, Service de rhumatologie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Department of Rheumatology, Lund University [Lund], Klinik für Dermatologie, Venerologie und Allergologie, Department of Pathophysiology, Medical School, University of Athens, Immuno-Rhumatologie Moléculaire, Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Lille, Droit et Santé, University of Northumbria at Newcastle [United Kingdom], Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, Department of Internal Medicine, Lupus Clinic, Sapienza University [Rome], Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Centre d'Investigation Clinique ( CIC - Brest ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Faculty of Chemistry and Chemical Technology, University of Ljubjana, University of Tsukuba, Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques ( CRESS - U1153 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Internal Medicine and section of Rheumatology, Villamarina Hospital, Immunologie des Maladies Virales et Autoimmunes ( IMVA - U1184 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Sorbonne Paris Cité (USPC), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), University of Ljubljana, Université de Tsukuba = University of Tsukuba, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Translational Immunology Groningen (TRIGR)

Subjects
Male, [SDV]Life Sciences [q-bio], Sjögren's Syndrome, Severity of Illness Index, law.invention, RESPONSIVENESS, Randomized controlled trial, law, EUROPEAN LEAGUE, Immunology and Allergy, Prospective Studies, Disease Activity, Outcomes research, Non-U.S. Gov't, Prospective cohort study, Fatigue, primary Sjögren ’ s syndrome, Research Support, Non-U.S. Gov't, Middle Aged, 3. Good health, Europe, Sjogren's Syndrome, REPORTED INDEX, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Female, Adult, medicine.medical_specialty, Immunology, Pain, Research Support, CONTROLLED-TRIAL, Xerostomia, General Biochemistry, Genetics and Molecular Biology, [ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatology, Internal medicine, Severity of illness, Xerophthalmia, medicine, Journal Article, Humans, Validation Studies, RITUXIMAB, Aged, [ SDV ] Life Sciences [q-bio], business.industry, Gold standard, Construct validity, Reproducibility of Results, HEALTH-STATUS INSTRUMENTS, medicine.disease, Physical therapy, Self Report, business, Rheumatism
Abstract

Objectives To validate the two recently developed disease activity indexes for assessment of primary Sjogren's syndrome (SS): the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI) and the EULAR SS Disease Activity Index (ESSDAI).Methods A prospective international 6-month duration validation study was conducted in 15 countries. At each visit, physicians completed ESSDAI, SS disease activity index (SSDAI), Sjogren's Systemic Clinical Activity Index (SCAI) and physician global assessment (PhGA); and patients completed ESSPRI, Sicca Symptoms Inventory (SSI), Profile of Fatigue and Discomfort (PROFAD) and patient global assessment (PGA). Psychometric properties (construct validity, responsiveness and reliability) were evaluated and compared between scores.Results Of the 395 patients included, 145 (37%) and 251 (64%) had currently active or current or past systemic manifestations, respectively. EULAR scores had higher correlation with the gold standard than other scores (ESSDAI with PhGA: r= 0.59; ESSRPI with PGA: r= 0.70). Correlations between patient and systemic scores were very low (ranging from 0.07 to 0.29). All systemic scores had similar large responsiveness in improved patients. Responsiveness of patient scores was low but was significantly higher for ESSPRI compared with SSI and PROFAD. Reliability was very good for all scores.Conclusions ESSDAI and ESSPRI had good construct validity. All scores were reliable. Systemic scores had a large sensitivity to change in patients whose disease activity improves. Patient scores had a small sensitivity to change, however, significantly better for ESSPRI. Systemic and patient scores poorly correlated, suggesting that they are 2 complementary components that should be both evaluated, but separately.

Published
2014
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10. Development of the ClinESSDAI : a clinical score without biological domain. A tool for biological studies

Author

Seror, Raphaèle, Meiners, Petra, Baron, Gabriel, Bootsma, Hendrika, Bowman, Simon J, Vitali, Claudio, Gottenberg, Jacques-Eric, Theander, Elke, Tzioufas, Athanasios, De Vita, Salvatore, Ramos-Casals, Manel, Dörner, Thomas, Quartuccio, Luca, Ravaud, Philippe, Mariette, Xavier, and EULAR Sjögren Task Force

Subjects
Journal Article, Validation Studies
Abstract

OBJECTIVE: To develop and validate ClinESSDAI (Clinical European League Against Rheumatism Sjögren's Syndrome Disease Activity Index), ie, ESSDAI without the biological domain. PATIENTS AND METHODS: The 702 fictive vignettes derived from 96 real cases of primary Sjögren's syndrome of the ESSDAI development study were used. As for ESSDAI development, the physician assessment of disease activity (0-10 scale) was used as the 'gold standard' in a multivariate model for weighting domains, after removing the biological domain. The reliability, assessed by intraclass correlation coefficient (ICC) between ClinESSDAI and ESSDAI, explored if ClinESSDAI was equivalent to ESSDAI. Its psychometric (ie, measurement) properties were compared with that of ESSDAI in an independent cohort. Also, its use was evaluated on data of two clinical trials. RESULTS: In multivariate modelling, all 11 domains remained significantly associated with disease activity, with slight modifications of some domain weights. Reliability between clinESSDAI and ESSDAI was excellent (ICC=0.98 and 0.99). Psychometric properties of clinESSDAI, disease activity levels and minimal clinically important improvement thresholds and its ability to detect change over time in clinical trials were very close to that of ESSDAI. CONCLUSIONS: ClinESSDAI appears valid and very close to the original ESSDAI. This score provides an accurate evaluation of disease activity independent of B-cell biomarkers. It could be used in various circumstances: (i) in biological/clinical studies to avoid data collinearity, (ii) in clinical trials, as secondary endpoint, to detect change independent of biological effect of the drug, (iii) in clinical practice to assess disease activity for visits where immunological tests have not been done.

Published
2016

11. Development of the ClinESSDAI: a clinical score without biological domain. A tool for biological studies

Author

Seror, Raphaèle, Meiners, Petra, Baron, Gabriel, Bootsma, Hendrika, Bowman, Simon J, Vitali, Claudio, Gottenberg, Jacques-Eric, Theander, Elke, Tzioufas, Athanasios, De Vita, Salvatore, Ramos-Casals, Manel, Dörner, Thomas, Quartuccio, Luca, Ravaud, Philippe, Mariette, Xavier, Bartoloni, Elena, Gerli, Roberto, Bombardieri, Stefano, Kallenberg, Cees, Brun, Johan G, Caporali, Roberto, Devauchelle, Valerie, Saraux, Alain, Fauchais, Anne-Laure, Gottenberg, Jacques Eric, Hachulla, Eric, Kruize, Aike A, Mandl, Thomas, Demoulins, Frederic, Bicêtre, Le Kremlin, Montecucco, Carlomaurizio, Ng, Wan-Fai, Praprotnik, Sonja, Tomsic, Matija, Casals, Manel Ramos, Scofield, Hal, Sivils, Kathy L., Laqué, Roser Solans, Sumida, Takayuki, Nishiyama, Sumusu, Valesini, Guido, Valim, Valeria, Vollenweider, Cristina, CHU Cochin [AP-HP], Departement of Oral and Maxillofacial Surgery, Groningen, Univesity of Medical Center Groningen, Education Discours Apprentissages (EDA - EA 4071), Université Paris Descartes - Paris 5 (UPD5), Department of Rheumatology and Clinical Immunology Groningen, University Medical Center Groningen [Groningen] (UMCG), Department of Internal Medicine and section of Rheumatology, Villamarina Hospital, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Rheumatology, Lund University [Lund], Department of Pathophysiology, Medical School, University of Athens, University of Udine and University Hospital of Udine, Laboratory of Autoimmune Diseases Josep Font Barcelona, CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona, Klinik für Dermatologie, Venerologie und Allergologie, University of Udine and University Hospital- Udine, Università degli Studi di Udine - University of Udine [Italie], Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de médecine interne, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of biomedical sciences, Universita degli Studi di Padova, University of Northumbria at Newcastle [United Kingdom], University Medical Centre, Faculty of Chemistry and Chemical Technology, University of Ljubjana, University of Tsukuba, Department of Internal Medicine, Lupus Clinic, Sapienza University [Rome], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-CHU Limoges, Université de Tsukuba = University of Tsukuba, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Translational Immunology Groningen (TRIGR), Education Discours Apprentissages ( EDA - EA 4071 ), Université Paris Descartes - Paris 5 ( UPD5 ), University Medical Center Groningen, Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Homéostasie Cellulaire et Pathologies ( HCP ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -CHU Limoges, and Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille )

Subjects
Genetics and Molecular Biology (all), Male, Multivariate statistics, Psychometrics, Intraclass correlation, INDEXES ESSPRI, Biochemistry, Severity of Illness Index, B-LYMPHOCYTE STIMULATOR, RESPONSIVENESS, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Disease Activity, Outcomes research, Sjøgren's Syndrome, Rheumatology, Immunology, Biochemistry, Genetics and Molecular Biology (all), 030212 general & internal medicine, SYSTEMIC-LUPUS-ERYTHEMATOSUS, ComputingMilieux_MISCELLANEOUS, MINIMAL DISEASE-ACTIVITY, Sjogren's Syndrome, Cohort, Sjøgren's Syndrome, Female, Humans, Reproducibility of Results, Sensitivity and Specificity, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.medical_specialty, PRIMARY SJOGRENS-SYNDROME, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Internal medicine, Severity of illness, medicine, Journal Article, Validation Studies, 030203 arthritis & rheumatology, business.industry, HEALTH-STATUS INSTRUMENTS, Gold standard (test), RHEUMATOID-ARTHRITIS, Clinical trial, DEFINITION, Physical therapy, business, ESSDAI
Abstract

ObjectiveTo develop and validate ClinESSDAI (Clinical European League Against Rheumatism Sjögren's Syndrome Disease Activity Index), ie, ESSDAI without the biological domain.Patients and methodsThe 702 fictive vignettes derived from 96 real cases of primary Sjögren's syndrome of the ESSDAI development study were used. As for ESSDAI development, the physician assessment of disease activity (0–10 scale) was used as the ‘gold standard’ in a multivariate model for weighting domains, after removing the biological domain. The reliability, assessed by intraclass correlation coefficient (ICC) between ClinESSDAI and ESSDAI, explored if ClinESSDAI was equivalent to ESSDAI. Its psychometric (ie, measurement) properties were compared with that of ESSDAI in an independent cohort. Also, its use was evaluated on data of two clinical trials.ResultsIn multivariate modelling, all 11 domains remained significantly associated with disease activity, with slight modifications of some domain weights. Reliability between clinESSDAI and ESSDAI was excellent (ICC=0.98 and 0.99). Psychometric properties of clinESSDAI, disease activity levels and minimal clinically important improvement thresholds and its ability to detect change over time in clinical trials were very close to that of ESSDAI.ConclusionsClinESSDAI appears valid and very close to the original ESSDAI. This score provides an accurate evaluation of disease activity independent of B-cell biomarkers. It could be used in various circumstances: (i) in biological/clinical studies to avoid data collinearity, (ii) in clinical trials, as secondary endpoint, to detect change independent of biological effect of the drug, (iii) in clinical practice to assess disease activity for visits where immunological tests have not been done.

Published
2016
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12. Early diagnosis of primary Sjögren's syndrome : EULAR-SS task force clinical recommendations

Author

Brito-Zerón, Pilar, Theander, Elke, Baldini, Chiara, Seror, Raphaèle, Retamozo, Soledad, Quartuccio, Luca, Bootsma, Hendrika, Bowman, Simon J, Dörner, Thomas, Gottenberg, Jacques-Eric, Mariette, Xavier, Bombardieri, Stefano, de Vita, Salvatore, Mandl, Thomas, Ng, Wan-Fai, Kruize, Aike A, Tzioufas, Athanasios, Vitali, Claudio, Buyon, Jill, Izmirly, Peter, Fox, Robert, Ramos-Casals, Manuel, and Eular Sjögren Syndrome Task Force

Subjects
Research Support, Non-U.S. Gov't, Journal Article, Sjögren syndrome, anti-Ro/SS-A antibodies, systemic activity, ESSDAI, classification criteria, focal lymphocytic sialadenitis, early diagnosis, Review
Abstract

Sjögren's syndrome (SjS) is a systemic autoimmune disease that mainly affects the exocrine glands, leading to generalized mucosal dryness. However, primary SjS may initially present with non-sicca (systemic) manifestations. When these features appear before the onset of an overt sicca syndrome, we may talk of an underlying 'occult' SjS. The European League Against Rheumatism (EULAR) has promoted and supported an international collaborative study group (EULAR-SS Task Force) aimed at developing consensual recommendations to provide a homogeneous approach to the patient with primary SjS presenting with systemic involvement. This review summarizes the key factors that should be taken into account in the diagnostic approach in a patient with suspected SjS according to the main clinical patterns of presentation, and is especially focused on organ-specific systemic disease presentations, including a consensus set of recommendations in order to reach an early diagnosis. Close collaboration with the different specialties involved through a comprehensive multidisciplinary approach is essential in SjS patients presenting with systemic involvements.

Published
2016

13. Anti-Porphyromonas gingivalis antibodies titres are associated with non-smoking status in early rheumatoid arthritis: Results from the ESPOIR cohort

Author

Seror, Raphaèle, Le Gall-David, Sandrine, Bonnaure-Mallet, Martine, Schaeverbeke, Thierry, Cantagrel, Alain, Minet, Jacques, Gottenberg, Jacques-Eric, Chanson, Philippe, Ravaud, Philippe, Mariette, Xavier, Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Microbiologie : Risques Infectieux, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes]-Faculté de Chirurgie Dentaire de Rennes-Faculté d'Odontologie-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de rhumatologie, CHU Bordeaux [Bordeaux], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Immuno-Rhumatologie Moléculaire, Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques ( CRESS - U1153 ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Faculté de Chirurgie Dentaire de Rennes-Faculté d'Odontologie-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), INSERM, Pfizer, AbbVie, French Society of Rheumatology, ESPOIR, The ESPOIR biological database, Roche-Chugai, Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Faculté de Chirurgie Dentaire de Rennes-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Jonchère, Laurent, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Sorbonne Paris Cité (USPC), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes - UFR d'Odontologie (UR Odontologie), and Université de Rennes (UR)-Université de Rennes (UR)

Subjects
[ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Smoking, Periodontal disease, Rheumatoid arthritis, ACPA, Porphyromonas gingivalis
Abstract

International audience; Objective To investigate the possible link between Porphyromonas gingivalis infection and rheumatoid arthritis (RA), according to antibody profile, genetic and environmental factors, and RA severity. Methods For assessing P gingivalis infection, serum levels of antibodies directed against P gingivalis lipopolysaccharide were measured in 694 patients with early RA who were not exposed to steroids or disease-modifying antirheumatic drugs. Anti–P gingivalis antibody titers were compared between patients with early RA and various control groups, and according to various patient characteristics. Results Anti–P gingivalis antibody titers did not significantly differ between patients with RA and controls and did not significantly differ with anti–citrullinated protein antibody (ACPA), rheumatoid factor (RF), or HLA shared epitope status. Anti–P gingivalis antibody titers were significantly higher among patients who had never smoked compared to patients who had ever smoked (P = 0.0049). Among nonsmokers, high anti–P gingivalis antibody levels were associated with a higher prevalence of erosive change (47.5% versus 33.3% with modified Sharp/van der Heijde score erosion subscale ≥1; P = 0.0135). Conclusion In this large early RA cohort, we did not detect any association of anti–P gingivalis antibodies with RA or with ACPA status. These results suggest that the association of periodontitis and RA could be linked to bacterial species other than P gingivalis or to a mechanism other than citrullination. Nevertheless, we found higher anti–P gingivalis antibody titers in nonsmokers. In addition, in this population of nonsmokers, high anti–P gingivalis antibody titers were associated with more severe disease. We hypothesize that the role of tobacco in RA pathogenesis is so high that the effect of P gingivalis could be revealed only in a population not exposed to tobacco.

Published
2015
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14. Analysis of anti Porphyromonas gingivalis (P. gingivalis) antibodies in a large cohort of patients with an early arthritis (ESPOIR)

Author

Seror , Raphaèle, Le Gall , Sylvain, Bonnaure-Mallet , Martine, Schaeverbeke , Thierry, Cantagrel , Alain, Mariette , Xavier, Brébion, Alice, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbiologie : Risques Infectieux, Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Faculté de Chirurgie Dentaire de Rennes-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), 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), Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Faculté de Chirurgie Dentaire de Rennes-Faculté d'Odontologie-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes - UFR d'Odontologie (UR Odontologie), Université de Rennes (UR)-Université de Rennes (UR), 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), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes]-Faculté de Chirurgie Dentaire de Rennes-Faculté d'Odontologie-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Physiopathologie de Toulouse Purpan ( CPTP ), Université Toulouse III - Paul Sabatier ( UPS ), 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 ), and Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
Published
2013

15. Role of Fms-like tyrosine kinase 3 ligand as a potential biologic marker of lymphoma in primary Sjögren's syndrome

Author

Tobón, Gabriel J, Saraux, Alain, Gottenberg, Jacques-Eric, Quartuccio, Luca, Fabris, Martina, Seror, Raphaèle, Devauchelle-Pensec, Valérie, Morel, Jacques, Rist, Stéphanie, Mariette, Xavier, De Vita, Salvatore, Youinou, Pierre, Pers, Jacques-Olivier, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Udine and University Hospital- Udine, Università degli Studi di Udine - University of Udine [Italie], University of Udine and University Hospital of Udine, CHU Cochin [AP-HP], Hôpital Lapeyronie [Montpellier] (CHU), Service de Médecine Interne, Hôpital Lariboisière, Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Bretagne Occidentale (UBO) - IFR148, Université de Bretagne Occidentale (UBO) - Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg - Institut National de la Santé et de la Recherche Médicale (INSERM) - Faculté de Médecine, University of Udine [Italy], CHU Cochin [APHP], Hôpital Lapeyronie, Université Montpellier 1 (UM1) - Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier) - Hôpital Lapeyronie, and Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris-Sud - Paris 11 (UP11)

Subjects
Adult, Male, Lymphoma, [SDV.IMM] Life Sciences [q-bio]/Immunology, Middle Aged, Severity of Illness Index, Sjogren's Syndrome, fms-Like Tyrosine Kinase 3, hemic and lymphatic diseases, Biomarkers, Tumor, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Aged
Abstract

International audience; OBJECTIVE: Patients with primary Sjögren's syndrome (SS) are at greater risk of developing lymphoma. This study was undertaken to evaluate whether the Fms-like tyrosine kinase 3 ligand (Flt-3L) might be associated with lymphoma in primary SS. METHODS: Serum levels of Flt-3L were measured in 369 patients with primary SS from the French Assessment of Systemic Signs and Evolution of Sjögren's Syndrome study cohort and in 10 patients with primary SS at the time of lymphoma diagnosis in an Italian cohort. Associations between increased levels of Flt-3L and a history of lymphoma, history of previously diagnosed criteria related to a high risk of lymphoma, and greater extent of disease activity were evaluated. RESULTS: Among patients with primary SS, higher levels of Flt-3L were significantly associated with a history of lymphoma (P = 0.0001). Previous markers for risk of lymphoma development, such as presence of purpura, low levels of C4, presence of lymphocytopenia, low levels of IgM, high levels of β2 -microglobulin, and a higher primary SS disease activity score, were all associated with higher levels of Flt-3L. The levels of Flt-3L were also increased in serum obtained from patients with primary SS at the time of lymphoma diagnosis. Furthermore, the Flt-3L levels were elevated in the serum of 6 patients up to 94 months (mean 46 months) prior to the diagnosis of lymphoma. Receiver operating characteristic curve analysis showed that an Flt-3L level of 175 pg/ml was the ideal cutoff value for demonstrating an association with lymphoma (specificity 97.5%, sensitivity 44%, negative predictive value 97%). CONCLUSION: Flt-3L is associated with lymphoma in primary SS, and constitutes a good biologic marker. Higher levels of this cytokine are present several years before the diagnosis of lymphoma, and may be useful as a predictive marker of lymphoproliferative disorders in primary SS.

Published
2013
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16. The FMS-like tyrosine kinase3-ligand is an immunological marker of lymphoma in primary Sjögren's syndrome

Author

Tobon, Gabriel J., Gottenberg, Jacques-Eric, Seror, Raphaèle, Devauchelle-Pensec, Valérie, Morel, Jacques, Rist, Stéphanie, Mariette, Xavier, Saraux, Alain, Youinou, Pierre, Pers, Jacques-Olivier, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service de rhumatologie, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Lapeyronie [Montpellier] (CHU), Service de Médecine Interne, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Immunologie et Immunothérapie, Michel, Geneviève, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2012

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