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1. Coronavirus disease 2019 in patients with inborn errors of immunity: An international study

Author

Meyts, Isabelle, Bucciol, Giorgia, Quinti, Isabella, Neven, Bénédicte, Fischer, Alain, Seoane, Elena, Lopez-Granados, Eduardo, Gianelli, Carla, Robles-Marhuenda, Angel, Jeandel, Pierre-Yves, Paillard, Catherine, Sankaran, Vijay G, Demirdag, Yesim Yilmaz, Lougaris, Vassilios, Aiuti, Alessandro, Plebani, Alessandro, Milito, Cinzia, Dalm, Virgil ASH, Guevara-Hoyer, Kissy, Sánchez-Ramón, Silvia, Bezrodnik, Liliana, Barzaghi, Federica, Gonzalez-Granado, Luis Ignacio, Hayman, Grant R, Uzel, Gulbu, Mendonça, Leonardo Oliveira, Agostini, Carlo, Spadaro, Giuseppe, Badolato, Raffaele, Soresina, Annarosa, Vermeulen, François, Bosteels, Cedric, Lambrecht, Bart N, Keller, Michael, Mustillo, Peter J, Abraham, Roshini S, Gupta, Sudhir, Ozen, Ahmet, Karakoc-Aydiner, Elif, Baris, Safa, Freeman, Alexandra F, Yamazaki-Nakashimada, Marco, Scheffler-Mendoza, Selma, Espinosa-Padilla, Sara, Gennery, Andrew R, Jolles, Stephen, Espinosa, Yazmin, Poli, M Cecilia, Fieschi, Claire, Hauck, Fabian, Cunningham-Rundles, Charlotte, Mahlaoui, Nizar, Errors of Immunity, IUIS Committee of Inborn, Warnatz, Klaus, Sullivan, Kathleen E, and Tangye, Stuart G

Subjects
Vaccine Related, Clinical Research, Pneumonia & Influenza, Prevention, Pediatric, Emerging Infectious Diseases, Pneumonia, Infectious Diseases, Lung, Biodefense, Rare Diseases, Good Health and Well Being, Adolescent, Adult, Aged, COVID-19, Child, Child, Preschool, Female, Genetic Diseases, Inborn, Humans, Immunologic Deficiency Syndromes, Infant, Infant, Newborn, Male, Middle Aged, Retrospective Studies, Risk Factors, SARS-CoV-2, Severity of Illness Index, Young Adult, primary immunodeficiencies, inborn errors of immunity, hypogammaglobulinemia, immune dysregulation, IUIS Committee of Inborn Errors of Immunity, Immunology, Allergy
Abstract

BackgroundThere is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe coronavirus disease 2019. This is relevant not only for these patients but also for the general population, because studies of IEIs can unveil key requirements for host defense.ObjectiveWe sought to describe the presentation, manifestations, and outcome of SARS-CoV-2 infection in IEI to inform physicians and enhance understanding of host defense against SARS-CoV-2.MethodsAn invitation to participate in a retrospective study was distributed globally to scientific, medical, and patient societies involved in the care and advocacy for patients with IEI.ResultsWe gathered information on 94 patients with IEI with SARS-CoV-2 infection. Their median age was 25 to 34 years. Fifty-three patients (56%) suffered from primary antibody deficiency, 9 (9.6%) had immune dysregulation syndrome, 6 (6.4%) a phagocyte defect, 7 (7.4%) an autoinflammatory disorder, 14 (15%) a combined immunodeficiency, 3 (3%) an innate immune defect, and 2 (2%) bone marrow failure. Ten were asymptomatic, 25 were treated as outpatients, 28 required admission without intensive care or ventilation, 13 required noninvasive ventilation or oxygen administration, 18 were admitted to intensive care units, 12 required invasive ventilation, and 3 required extracorporeal membrane oxygenation. Nine patients (7 adults and 2 children) died.ConclusionsThis study demonstrates that (1) more than 30% of patients with IEI had mild coronavirus disease 2019 (COVID-19) and (2) risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients with IEI, including more younger patients. Further studies will identify pathways that are associated with increased risk of severe disease and are nonredundant or redundant for protection against SARS-CoV-2.

Published
2021

3. Activated phosphoinositide 3‐dinase delta syndrome (APDS): An update

Author

Vassilios Lougaris, Caterina Cancrini, Beatrice Rivalta, Riccardo Castagnoli, Giuliana Giardino, Stefano Volpi, Lucia Leonardi, Francesco La Torre, Silvia Federici, Stefania Corrente, Bianca Laura Cinicola, Annarosa Soresina, Gian Luigi Marseglia, Fabio Cardinale, Lougaris, V., Cancrini, C., Rivalta, B., Castagnoli, R., Giardino, G., Volpi, S., Leonardi, L., La Torre, F., Federici, S., Corrente, S., Cinicola, B. L., Soresina, A., Marseglia, G. L., and Cardinale, F.

Subjects
p85, activated phosphoinositide 3-kinase delta syndrome, lymphoproliferation, Class I Phosphatidylinositol 3-Kinases, p110δ, Primary Immunodeficiency Diseases, Immunology, Phosphatidylinositols, clinical research, immune dysregulation, primary combined immune deficiency, Phosphatidylinositol 3-Kinases, Settore MED/02, Humans, Mutation, Quality of Life, Pediatrics, Perinatology and Child Health, Immunology and Allergy
Abstract

Activated phosphoinositide 3-kinase delta syndrome (APDS) is a recently described form of inborn error of immunity (IEI) caused by heterozygous mutations in PIK3CD or PIK3R1 genes, respectively, encoding leukocyte-restricted catalytic p110δ subunit and the ubiquitously expressed regulatory p85 α subunit of the phosphoinositide 3-kinase δ (PI3Kδ). The first described patients with respiratory infections, hypogammaglobulinemia with normal to elevated IgM serum levels, lymphopenia, and lymphoproliferation. Since the original description, it is becoming evident that the onset of disease may be somewhat variable over time, both in terms of age at presentation and in terms of clinical and immunological complications. In many cases, patients are referred to various specialists such as hematologists, rheumatologists, gastroenterologists, and others, before an immunological evaluation is performed, leading to delay in diagnosis, which negatively affects their prognosis. The significant heterogeneity in the clinical and immunological features affecting APDS patients requires awareness among clinicians since good results with p110δ inhibitors have been reported, certainly ameliorating these patients’ quality of life and prognosis.

Published
2022

4. Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations

Author

Tim Niehues, Catherine Waruiru, Conleth Feighery, Uwe Schauer, Virginie Courteille, Kai Lehmberg, Ingo Müller, I. Esteves, Henner Morbach, Michael Borte, Patrick Hundsdoerfer, Klaus Schwarz, Ewelina Gowin, Alessandro Aiuti, Andreas Holbro, Federica Barzaghi, João Farela Neves, Dagmar Graf, Hannah Tamary, Veneta Milenova, Benedikt Boetticher, Eleonora Gambineri, Vera Goda, Alia Eldash, Jan-Christian Wasmuth, Fabio Candotti, Svetlana O. Sharapova, Markus Metzler, Juergen Brunner, Anna Hilfanova, Brindusa Ruxandra Capilna, Pere Soler-Palacín, Arnau Antolí, Horst von Bernuth, Vassilios Lougaris, Maria Carrabba, Bernd H. Belohradsky, Julian Thalhammer, Nathalie de Vergnes, Peter Olbrich, Peter Kopač, Leif G. Hanitsch, Alexandra Nieters, Filomeen Haerynck, Juliana Gabzdilova, Sezin Aydemir, Rabab El Hawary, Patrick F.K. Yong, Maria Giovanna Danieli, Alberto Tommasini, Sandra Steinmann, Ulrich Baumann, Figen Dogu, Elisabeth Förster-Waldl, Carolina Marasco, Donato Amodio, Lorenzo Lodi, Xavier Solanich, Caterina Cancrini, Brigita Sitkauskiene, Torsten Witte, Clementina Vanessa, Nima Rezaei, Jean-Christophe Goffard, Kirsten Wittke, Emmanouil Liatsis, Helen Baxendale, Susana L. Silva, Bodo Grimbacher, Henrike Ritterbusch, Evangelia Farmaki, Safa Meshaal, Sujal Ghosh, Larysa Kostyuchenko, David Edgar, Simone Cesaro, R Zeuner, Nerea Salmón Rodríguez, Isabella Quinti, Stephan Ehl, Pauline Brosselin, Joerg C. Henes, Pilar Llobet Agulló, Rosa Maria Dellepiane, Andrea Meinhardt, Marina Kojić, Georgios Sogkas, Stephan Borte, Catharina Schuetz, Suheyla Ocak, Karin Marschall, Lukas M. Gasteiger, Stefan Raffac, Sofia Tantou, Sadia Noorani, Matthaios Speletas, Philippe Randrianomenjanahary, Ursula Holzer, Ayca Kiykim, Johannes G. Liese, Angelo Vacca, Gisela Fecker, Ekrem Unal, Koen J. van Aerde, Alba Parra-Martínez, Kaan Boztug, Sophie Stiehler, Sybille Landwehr-Kenzel, Claudio Pignata, Jennifer Neubert, Janine Reichenbach, Shahnaz Parvin, Sarah Goddard, Andrea Schroll, Dirk Holzinger, Asghar Aghamohammadi, Hassan Abolhassani, Johannes Trück, Estela Paz-Artal, Shereen M. Reda, Anna Shcherbina, Maria Raptaki, Jaroslava Orosova, Beata Wolska-Kuśnierz, Tessa Kerre, Gerrit Ahrenstorf, Ben Zion Garty, Dirk Foell, Benjamin Becker, Ulrike F. Demel, Androniki Kapousouzi, Abraham Rutgers, Klaus Warnatz, Gemma Rocamora Blanch, Stephan Rusch, Luis M. Allende, Dalia Abd Elaziz, Safa Baris, Jorisvan Montfrans, Dominik T. Schneider, Raphael Scheible, Juana Gil-Herrera, Gerhard Kindle, Annarosa Soresina, Giovanna Fabio, Uwe Wintergerst, Emilia Faria, Maria Fasshauer, Silvia Ricci, Aisha Elmarsafy, Barbara Pietrucha, Carsten Speckmann, Nizar Mahlaoui, Ulrich Heininger, Isabelle Meyts, Matthew Buckland, Efimia Papadopoulou-Alataki, Robin Kobbe, A Herwadkar, Sebastian F. N. Bode, Ali Sobh, László Maródi, Baldassarre Martire, Chiara Azzari, Maximilian Heeg, Katja Masjosthusmann, Michael H. Albert, Matteo Chinello, Juan Luis Santos-Pérez, Aarnoud Huissoon, Tanya I. Coulter, Hendrik Schulze-Koops, Norbert Graf, Radwa Alkady, Jolanta Bernatoniene, Seraina Prader, Alenka Gagro, Joachim Roesler, Taco W. Kuijpers, Ewa Więsik-Szewczyk, Maria Elena Maccari, Conrad Ferdinand Lippert, Miriam González-Amores, Johannes Dirks, Daniel E Pleguezuelo, Christof M. Kramm, Anders Fasth, Volker Schuster, Olov Ekwall, Nikolaus Rieber, Javier Carbone, Petra Kaiser-Labusch, Diana Ernst, Lucia Augusta Baselli, Luis Ignacio Gonzalez-Granado, Maria Kanariou, Stefanie S. V. Henriet, Sigune Goldacker, Kerstin Felgentreff, Oana Joean, Fine Roosens, Fabian Hauck, Eva C. Schwaneck, Milos Jesenak, Manfred Hoenig, Lenka Kapustova, Christoph Boesecke, Alain Fischer, Sara Pereira da Silva, Julia Körholz, Ansgar Schulz, Carolynne Schwarze-Zander, Mikko Seppänen, Nermeen Galal, Nora Naumann-Bartsch, Tomaz Garcez, Peter Ciznar, Klara M. Posfay-Barbe, Zelimir Pavle Eric, Reinhold E. Schmidt, Hermann J. Girschick, Sabine Heine, Anika-Kerstin Biegner, Annick A. J. M. van de Ven, Stefan Schreiber, J. Merlijn van den Berg, Nurit Assia Batzir, Alexandra Jablonka, Kim Stol, Gregor Dückers, Antonios G.A. Kolios, Ioannis Kakkas, Christian Klemann, Marina N. Guseva, Sofia Grigoriadou, Elif Karakoc-Aydiner, Antonio Marzollo, Peter D. Arkwright, Urs C. Steiner, Sara Sebnem Kilic, Romina Dieli-Crimi, Gergely Kriván, Monika Sparber-Sauer, Marco Cazzaniga, Fulvio Porta, Paraskevi Maggina, Tomas Milota, Robbert G. M. Bredius, Martine Pergent, Klaus Tenbrock, Jana Pachlopnik Schmid, Florentia Dimitriou, Cathal Laurence Steele, Helen Bourne, Anna Bobcakova, Gerd Horneff, Judith Potjewijd, Marc Schmalzing, Tobias Ankermann, Paul Ryan, Oksana Boyarchuk, Necil Kutukculer, Carl Friedrich Classen, Zita Chovancová, Moira Thomas, Cinzia Milito, Michaela Bitzenhofer-Grüber, Faranaz Atschekzei, Eva Hlaváčková, Viviana Moschese, Julie Smet, Hans-Hartmut Peter, Carla Teixeira, Sabine M El-Helou, Suzanne de Kruijf Bazen, Helmut Wittkowski, Donate Jakoby, Marina Garcia-Prat, Esther de Vries, Richard Herriot, Sven Kracker, Alessandro Plebani, Lisa Göschl, Laura Hora Marques, Anna Sediva, Jiri Litzman, Mark M. Gompels, Renate Krüger, Şefika İlknur Kökçü Karadağ, Nadine Binder, Anna Szaflarska, Peter Jandus, Lisa Ibberson, Johann Greil, Ulf Schulze-Sturm, Mehtap Sirin, Aydan Ikinciogullari, Edyta Heropolitańska-Pliszka, Michael E. Weiss, Alla Skapenko, Lukas Wisgrill, Hana Alachkar, Uta Behrends, Silvia Sánchez-Ramón, Maria N. Hatzistilianou, Otilia Petrovicova, Darko Richter, Zoreh Nademi, Jürgen K. Rockstroh, Sohilla Lotfy, Markus G. Seidel, Timothy Ronan Leahy, Audra Blažienė, Translational Immunology Groningen (TRIGR), Paediatric Infectious Diseases / Rheumatology / Immunology, AII - Inflammatory diseases, ARD - Amsterdam Reproduction and Development, University of Zurich, Ehl, Stephan, Thalhammer, J., Kindle, G., Nieters, A., Rusch, S., Seppanen, M. R. J., Fischer, A., Grimbacher, B., Edgar, D., Buckland, M., Mahlaoui, N., Ehl, S., Boztug, K., Brunner, J., Demel, U. F., Forster-Waldl, E., Gasteiger, L. M., Goschl, L., Kojic, M., Schroll, A., Seidel, M. G., Wintergerst, U., Wisgrill, L., Sharapova, S. O., Goffard, J. -C., Kerre, T., Meyts, I., Roosens, F., Smet, J., Haerynck, F., Eric, Z. P., Milenova, V., Gagro, A., Richter, D., Chovancova, Z., Hlavackova, E., Litzman, J., Milota, T., Sediva, A., Elaziz, D. A., Alkady, R. S., El Sayed El Hawary, R., Eldash, A. S., Galal, N., Lotfy, S., Meshaal, S. S., Reda, S. M., Sobh, A., Elmarsafy, A., Brosselin, P., Courteille, V., De Vergnes, N., Kracker, S., Pergent, M., Randrianomenjanahary, P., Ahrenstorf, G., Albert, M. H., Ankermann, T., Atschekzei, F., Baumann, U., Becker, B. C., Behrends, U., Belohradsky, B. H., Biegner, A. -K., Binder, N., Bode, S. F. N., Boesecke, C., Boetticher, B., Borte, M., Borte, S., Classen, C. F., Dirks, J., Duckers, G., El-Helou, S., Ernst, D., Fasshauer, M., Fecker, G., Felgentreff, K., Foell, D., Ghosh, S., Girschick, H. J., Goldacker, S., Graf, N., Graf, D., Greil, J., Hanitsch, L. G., Hauck, F., Heeg, M., Heine, S. I., Henes, J. C., Hoenig, M., Holzer, U., Holzinger, D., Horneff, G., Hundsdoerfer, P., Jablonka, A., Jakoby, D., Joean, O., Kaiser-Labusch, P., Klemann, C., Kobbe, R., Korholz, J., Kramm, C. M., Kruger, R., Landwehr-Kenzel, S., Lehmberg, K., Liese, J. G., Lippert, C. F., Maccari, M. E., Masjosthusmann, K., Meinhardt, A., Metzler, M., Morbach, H., Muller, I., Naumann-Bartsch, N., Neubert, J., Niehues, T., Peter, H. -H., Rieber, N., Ritterbusch, H., Rockstroh, J. K., Roesler, J., Schauer, U., Scheible, R., Schmalzing, M., Schmidt, R. E., Schneider, D. T., Schreiber, S., Schuetz, C., Schulz, A., Schulze-Koops, H., Schulze-Sturm, U., Schuster, V., Schwaneck, E. C., Schwarz, K., Schwarze-Zander, C., Sirin, M., Skapenko, A., Sogkas, G., Sparber-Sauer, M., Speckmann, C., Steinmann, S., Stiehler, S., Tenbrock, K., von Bernuth, H., Warnatz, K., Wasmuth, J. -C., Weiss, M., Witte, T., Wittke, K., Wittkowski, H., Zeuner, R. A., Farmaki, E., Hatzistilianou, M. N., Kakkas, I., Kanariou, M. G., Kapousouzi, A., Liatsis, E., Maggina, P., Papadopoulou-Alataki, E., Raptaki, M., Speletas, M., Tantou, S., Goda, V., Krivan, G., Marodi, L., Abolhassani, H., Aghamohammadi, A., Rezaei, N., Feighery, C., Leahy, T. R., Ryan, P., Batzir, N. A., Garty, B. Z., Tamary, H., Aiuti, A., Amodio, D., Azzari, C., Barzaghi, F., Baselli, L. A., Cancrini, C., Carrabba, M., Cazzaniga, M., Cesaro, S., Chinello, M., Danieli, M. G., Dellepiane, R. M., Fabio, G., Gambineri, E., Lodi, L., Lougaris, V., Marasco, C., Martire, B., Marzollo, A., Milito, C., Moschese, V., Pignata, C., Plebani, A., Porta, F., Quinti, I., Ricci, S., Soresina, A., Tommasini, A., Vacca, A., Vanessa, C., Blaziene, A., Sitkauskiene, B., Gowin, E., Heropolitanska-Pliszka, E., Pietrucha, B., Szaflarska, A., Wiesik-Szewczyk, E., Wolska-Kusnierz, B., Esteves, I., Faria, E., Marques, L. H., Neves, J. F., Silva, S. L., Teixeira, C., Pereira da Silva, S., Capilna, B. R., Guseva, M. N., Shcherbina, A., Bobcakova, A., Ciznar, P., Gabzdilova, J., Jesenak, M., Kapustova, L., Orosova, J., Petrovicova, O., Raffac, S., Kopac, P., Allende, L. M., Antoli, A., Blanch, G. R., Carbone, J., Dieli-Crimi, R., Garcia-Prat, M., Gil-Herrera, J., Gonzalez-Granado, L. I., Agullo, P. L., Olbrich, P., Parra-Martinez, A., Paz-Artal, E., Pleguezuelo, D. E., Rodriguez, N. S., Sanchez-Ramon, S., Santos-Perez, J. L., Solanich, X., Soler-Palacin, P., Gonzalez-Amores, M., Ekwall, O., Fasth, A., Bitzenhofer-Gruber, M., Candotti, F., Dimitriou, F., Heininger, U., Holbro, A., Jandus, P., Kolios, A. G. A., Marschall, K., Schmid, J. P., Posfay-Barbe, K. M., Prader, S., Reichenbach, J., Steiner, U. C., Truck, J., Bredius, R. G., de Kruijf- Bazen, S., de Vries, E., Henriet, S. S. V., Kuijpers, T. W., Potjewijd, J., Rutgers, A., Stol, K., van Aerde, K. J., Van den Berg, J. M., van de Ven, A. A. J. M., Montfrans, J., Aydemir, S., Baris, S., Dogu, F., Ikinciogullari, A., Karakoc-Aydiner, E., Kilic, S. S., Kiykim, A., Kokcu Karadag, S. I., Kutukculer, N., Ocak, S., Unal, E., Boyarchuk, O., Hilfanova, A., Kostyuchenko, L. V., Alachkar, H., Arkwright, P. D., Baxendale, H. E., Bernatoniene, J., Coulter, T. I., Garcez, T., Goddard, S., Gompels, M. M., Grigoriadou, S., Herriot, R., Herwadkar, A., Huissoon, A., Ibberson, L., Nademi, Z., Noorani, S., Parvin, S., Steele, C. L., Thomas, M., Waruiru, C., Yong, P. F. K., and Bourne, H.

Subjects
0301 basic medicine, Male, Pediatrics, syndromic, Sex Factor, Disease, registry, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Primary Immunodeficiency Disease, inborn error of immunity, Immunology and Allergy, warning signs, Age Factor, Registries, Family history, presenting symptom, Child, Primary immunodeficiency, Granuloma, autoimmune, immune dysregulation, inflammatory, Adult, Autoimmune Diseases, Female, Humans, Infections, Lymphoproliferative Disorders, Middle Aged, Primary Immunodeficiency Diseases, Sex Factors, Age Factors, 10177 Dermatology Clinic, Infections/epidemiology, 3. Good health, Settore MED/02, Warning signs, Lymphoproliferative Disorder, 2723 Immunology and Allergy, Infection, Human, medicine.medical_specialty, Immunology, 610 Medicine & health, Malignancy, primary immunodeficiency, Autoimmune Disease, 03 medical and health sciences, Immunity, Autoimmune Diseases/epidemiology, medicine, 2403 Immunology, business.industry, warning sign, Common variable immunodeficiency, Granuloma/epidemiology, Immune dysregulation, medicine.disease, Primary Immunodeficiency Diseases/epidemiology, 030104 developmental biology, Lymphoproliferative Disorders/epidemiology, Cohort Studie, business, 030215 immunology
Abstract

BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

Published
2021

5. Progressive Depletion of B and T Lymphocytes in Patients with Ataxia Telangiectasia: Results of the Italian Primary Immunodeficiency Network

Author

Emilia Cirillo, Agata Polizzi, Annarosa Soresina, Rosaria Prencipe, Giuliana Giardino, Caterina Cancrini, Andrea Finocchi, Beatrice Rivalta, Rosa M. Dellepiane, Lucia A. Baselli, Davide Montin, Antonino Trizzino, Rita Consolini, Chiara Azzari, Silvia Ricci, Lorenzo Lodi, Isabella Quinti, Cinzia Milito, Lucia Leonardi, Marzia Duse, Maria Carrabba, Giovanna Fabio, Patrizia Bertolini, Paola Coccia, Irene D’Alba, Andrea Pession, Francesca Conti, Marco Zecca, Claudio Lunardi, Manuela Lo Bianco, Santiago Presti, Laura Sciuto, Roberto Micheli, Dario Bruzzese, Vassilios Lougaris, Raffaele Badolato, Alessandro Plebani, Luciana Chessa, Claudio Pignata, Cirillo, E., Polizzi, A., Soresina, A., Prencipe, R., Giardino, G., Cancrini, C., Finocchi, A., Rivalta, B., Dellepiane, R. M., Baselli, L. A., Montin, D., Trizzino, A., Consolini, R., Azzari, C., Ricci, S., Lodi, L., Quinti, I., Milito, C., Leonardi, L., Duse, M., Carrabba, M., Fabio, G., Bertolini, P., Coccia, P., D'Alba, I., Pession, A., Conti, F., Zecca, M., Lunardi, C., Bianco, M. L., Presti, S., Sciuto, L., Micheli, R., Bruzzese, D., Lougaris, V., Badolato, R., Plebani, A., Chessa, L., and Pignata, C.

Subjects
B lymphocyte, T-Lymphocytes, genotype, Immunology, T lymphocytes, Ataxia Telangiectasia Mutated Proteins, lymphopenia, primary immunodeficiency, Settore MED/02, Mutation, Humans, Ataxia telangiectasia, B lymphocytes, Immunology and Allergy, Retrospective Studies
Abstract

Ataxia telangiectasia (AT) is a rare neurodegenerative genetic disorder due to bi-allelic mutations in the Ataxia Telangiectasia Mutated (ATM) gene. The aim of this paper is to better define the immunological profile over time, the clinical immune-related manifestations at diagnosis and during follow-up, and to attempt a genotype–phenotype correlation of an Italian cohort of AT patients. Retrospective data of 69 AT patients diagnosed between December 1984 and November 2019 were collected from the database of the Italian Primary Immunodeficiency Network. Patients were classified at diagnosis as lymphopenic (Group A) or non-lymphopenic (Group B). Fifty eight out of 69 AT patients (84%) were genetically characterized and distinguished according to the type of mutations in truncating/truncating (TT; 27 patients), non-truncating (NT)/T (28 patients), and NT/NT (5 patients). In 3 patients, only one mutation was detected. Data on age at onset and at diagnosis, cellular and humoral compartment at diagnosis and follow-up, infectious diseases, signs of immune dysregulation, cancer, and survival were analyzed and compared to the genotype. Lymphopenia at diagnosis was related per se to earlier age at onset. Progressive reduction of cellular compartment occurred during the follow-up with a gradual reduction of T and B cell number. Most patients of Group A carried bi-allelic truncating mutations, had a more severe B cell lymphopenia, and a reduced life expectancy. A trend to higher frequency of interstitial lung disease, immune dysregulation, and malignancy was noted in Group B patients. Lymphopenia at the onset and the T/T genotype are associated with a worst clinical course. Several mechanisms may underlie the premature and progressive immune decline in AT subjects.

Published
2022

6. The Impact of SARS-CoV-2 Infection in Patients with Inborn Errors of Immunity: the Experience of the Italian Primary Immunodeficiencies Network (IPINet)

Author

Giuliana Giardino, Cinzia Milito, Vassilios Lougaris, Alessandra Punziano, Maria Carrabba, Francesco Cinetto, Riccardo Scarpa, Rosa Maria Dellepiane, Silvia Ricci, Beatrice Rivalta, Francesca Conti, Antonio Marzollo, Davide Firinu, Emilia Cirillo, Gianluca Lagnese, Caterina Cancrini, Baldassare Martire, Maria Giovanna Danieli, Andrea Pession, Angelo Vacca, Chiara Azzari, Giovanna Fabio, Annarosa Soresina, Carlo Agostini, Giuseppe Spadaro, Raffaele Badolato, Maria Pia Cicalese, Alessandro Aiuti, Alessandro Plebani, Isabella Quinti, Claudio Pignata, Giardino, Giuliana, Milito, Cinzia, Lougaris, Vassilio, Punziano, Alessandra, Carrabba, Maria, Cinetto, Francesco, Scarpa, Riccardo, Dellepiane, Rosa Maria, Ricci, Silvia, Rivalta, Beatrice, Conti, Francesca, Marzollo, Antonio, Firinu, Davide, Cirillo, Emilia, Lagnese, Gianluca, Cancrini, Caterina, Martire, Baldassare, Danieli, Maria Giovanna, Pession, Andrea, Vacca, Angelo, Azzari, Chiara, Fabio, Giovanna, Soresina, Annarosa, Agostini, Carlo, Spadaro, Giuseppe, Badolato, Raffaele, Cicalese, Maria Pia, Aiuti, Alessandro, Plebani, Alessandro, Quinti, Isabella, and Pignata, Claudio

Subjects
Adult, Male, SARS-CoV-2, COVID-19, Inborn errors of immunity, Outcome, Seroconversion, Viral shedding, Immunology, Hospitalization, Common Variable Immunodeficiency, Post-Acute COVID-19 Syndrome, Settore MED/02, Immunology and Allergy, Humans, Female, Child, Retrospective Studies
Abstract

COVID-19 manifestations range from asymptomatic to life-threatening infections. The outcome in different inborn errors of immunity (IEI) is still a matter of debate. In this retrospective study, we describe the experience of the of the Italian Primary Immunodeficiencies Network (IPINet). Sixteen reference centers for adult or pediatric IEI were involved. One hundred fourteen patients were enrolled including 35 pediatric and 79 adult patients. Median age was 32 years, and male-to-female ratio was 1.5:1. The most common IEI were 22q11.2 deletion syndrome in children (26%) and common variable immunodeficiency (CVID) in adults (65%). Ninety-one patients did not require hospital admission, and among these, 33 were asymptomatic. Hospitalization rate was 20.17%. Older age (p 0.004) and chronic lung disease (p 0.0008) represented risk factors for hospitalization. Hospitalized patients mainly included adults suffering from humoral immunodeficiencies requiring immunoglobulin replacement therapy and as expected had lower B cell counts compared to non-hospitalized patients. Infection fatality rate in the whole cohort was 3.5%. Seroconversion was observed is 86.6% of the patients evaluated and in 83.3% of CVID patients. 16.85% of the patients reported long-lasting COVID symptoms. All but one patient with prolonged symptoms were under IgRT. The fatality rate observed in IEI was slightly similar to the general population. The age of the patients who did not survive was lower compared to the general population, and the age stratified mortality in the 50–60 age range considerable exceeded the mortality from 50 to 60 age group of the Italian population (14.3 vs 0.6%; p

Published
2022

7. Coronavirus disease 2019 in patients with inborn errors of immunity: An international study

Author

Liliana Bezrodnik, Vijay G. Sankaran, Silvia Sánchez-Ramón, Peter Mustillo, Michael A. Keller, Isabelle Meyts, Giorgia Bucciol, Yesim Yilmaz Demirdag, Luis Ignacio Gonzalez-Granado, Andrew R. Gennery, Alexandra F. Freeman, Raffaele Badolato, Alain Fischer, Safa Baris, Federica Barzaghi, Sudhir Gupta, Carlo Agostini, Gulbu Uzel, Kissy Guevara-Hoyer, Isabella Quinti, M. Cecilia Poli, Charlotte Cunningham-Rundles, Stephen Jolles, Elif Karakoc-Aydiner, Alessandro Aiuti, Cinzia Milito, Fabian Hauck, Angel Robles-Marhuenda, Stuart G. Tangye, Marco Yamazaki-Nakashimada, Elena Seoane, Sara Elva Espinosa-Padilla, Pierre Yves Jeandel, Kathleen E. Sullivan, Klaus Warnatz, Claire Fieschi, Cedric Bosteels, Alessandro Plebani, Leonardo Oliveira Mendonça, Carla Gianelli, François Vermeulen, Bart N. Lambrecht, Annarosa Soresina, Virgil A. S. H. Dalm, Selma Scheffler-Mendoza, Catherine Paillard, Eduardo López-Granados, Vassilios Lougaris, Ahmet Ozen, Grant Hayman, Nizar Mahlaoui, Yazmin Espinosa, Bénédicte Neven, Giuseppe Spadaro, Roshini S. Abraham, Meyts, Isabelle, Bucciol, Giorgia, Quinti, Isabella, Neven, Bénédicte, Fischer, Alain, Seoane, Elena, Lopez-Granados, Eduardo, Gianelli, Carla, Robles-Marhuenda, Angel, Jeandel, Pierre-Yve, Paillard, Catherine, Sankaran, Vijay G, Demirdag, Yesim Yilmaz, Lougaris, Vassilio, Aiuti, Alessandro, Plebani, Alessandro, Milito, Cinzia, Dalm, Virgil Ash, Guevara-Hoyer, Kissy, Sánchez-Ramón, Silvia, Bezrodnik, Liliana, Barzaghi, Federica, Gonzalez-Granado, Luis Ignacio, Hayman, Grant R, Uzel, Gulbu, Mendonça, Leonardo Oliveira, Agostini, Carlo, Spadaro, Giuseppe, Badolato, Raffaele, Soresina, Annarosa, Vermeulen, Françoi, Bosteels, Cedric, Lambrecht, Bart N, Keller, Michael, Mustillo, Peter J, Abraham, Roshini S, Gupta, Sudhir, Ozen, Ahmet, Karakoc-Aydiner, Elif, Baris, Safa, Freeman, Alexandra F, Yamazaki-Nakashimada, Marco, Scheffler-Mendoza, Selma, Espinosa-Padilla, Sara, Gennery, Andrew R, Jolles, Stephen, Espinosa, Yazmin, Poli, M Cecilia, Fieschi, Claire, Hauck, Fabian, Cunningham-Rundles, Charlotte, Mahlaoui, Nizar, Warnatz, Klau, Sullivan, Kathleen E, Tangye, Stuart G, Meyts, I., Bucciol, G., Quinti, I., Neven, B., Fischer, A., Seoane, E., Lopez-Granados, E., Gianelli, C., Robles-Marhuenda, A., Jeandel, P. -Y., Paillard, C., Sankaran, V. G., Demirdag, Y. Y., Lougaris, V., Aiuti, A., Plebani, A., Milito, C., Dalm, V. A., Guevara-Hoyer, K., Sanchez-Ramon, S., Bezrodnik, L., Barzaghi, F., Gonzalez-Granado, L. I., Hayman, G. R., Uzel, G., Mendonca, L. O., Agostini, C., Spadaro, G., Badolato, R., Soresina, A., Vermeulen, F., Bosteels, C., Lambrecht, B. N., Keller, M., Mustillo, P. J., Abraham, R. S., Gupta, S., Ozen, A., Karakoc-Aydiner, E., Baris, S., Freeman, A. F., Yamazaki-Nakashimada, M., Scheffler-Mendoza, S., Espinosa-Padilla, S., Gennery, A. R., Jolles, S., Espinosa, Y., Poli, M. C., Fieschi, C., Hauck, F., Cunningham-Rundles, C., Mahlaoui, N., Warnatz, K., Sullivan, K. E., Tangye, S. G., Internal Medicine, Neven, Benedicte, Lopez-Grandos, Eduardo, Jeandel, Pierre-Yves, Sankaran, Vijay G., Lougaris, Vassilios, Dalm, Virgil A. S. H., Sanchez-Ramon, Silvia, Ignacio Gonzalez-Granado, Luis, Hayman, Grant R., Mendonca, Leonardo Oliveira, Vermeulen, Francois, Lambrecht, Bart N., Mustillo, Peter J., Abraham, Roshini S., Freeman, Alexandra F., Gennery, Andrew R., Poli, M. Cecilia, Warnatz, Klaus, Sullivan, Kathleen E., and Tangye, Stuart G.

Subjects
0301 basic medicine, Male, inborn errors of immunity, X-CGD, X-linked chronic granulomatous disease, CGD, Chronic granulomatous disease, X-SCID, X-linked severe combined immunodeficiency, medicine.disease_cause, Severity of Illness Index, law.invention, HSCT, Hematopoietic stem cell transplantation, 0302 clinical medicine, law, Risk Factors, PID, Primary immunodeficiency, AIHA, Autoimmune hemolytic anemia, Medicine and Health Sciences, Immunology and Allergy, Child, Immunodeficiency, education.field_of_study, COVID-19, Coronavirus disease 2019, Middle Aged, Intensive care unit, ICU, Intensive care unit, Child, Preschool, ALPS, Autoimmune lymphoproliferative syndrome, Female, CVID, Common variable immune deficiency, primary immunodeficiencies, Adult, medicine.medical_specialty, IEI, Inborn errors of immunity, Adolescent, hypogammaglobulinemia, Population, Immunology, P, Patient, 03 medical and health sciences, Young Adult, immune dysregulation, Internal medicine, Intensive care, Severity of illness, medicine, Humans, education, Aged, Retrospective Studies, AR, Autosomal-recessive, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, business.industry, SARS-CoV-2, AGS, Aicardi-Goutieres syndrome, Genetic Diseases, Inborn, Immunologic Deficiency Syndromes, Infant, Newborn, Infant, COVID-19, Retrospective cohort study, Immune dysregulation, medicine.disease, HLH, Hemophagocytic lymphohistiocytosis, 030104 developmental biology, Primary immunodeficiency, CID, Combined immunodeficiency, business, 030215 immunology
Abstract

BACKGROUND: There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe coronavirus disease 2019. This is relevant not only for these patients but also for the general population, because studies of IEIs can unveil key requirements for host defense. OBJECTIVE: We sought to describe the presentation, manifestations, and outcome of SARS-CoV-2 infection in IEI to inform physicians and enhance understanding of host defense against SARS-CoV-2. METHODS: An invitation to participate in a retrospective study was distributed globally to scientific, medical, and patient societies involved in the care and advocacy for patients with IEI. RESULTS: We gathered information on 94 patients with IEI with SARS-CoV-2 infection. Their median age was 25 to 34 years. Fifty-three patients (56%) suffered from primary antibody deficiency, 9 (9.6%) had immune dysregulation syndrome, 6 (6.4%) a phagocyte defect, 7 (7.4%) an autoinflammatory disorder, 14 (15%) a combined immunodeficiency, 3 (3%) an innate immune defect, and 2 (2%) bone marrow failure. Ten were asymptomatic, 25 were treated as outpatients, 28 required admission without intensive care or ventilation, 13 required noninvasive ventilation or oxygen administration, 18 were admitted to intensive care units, 12 required invasive ventilation, and 3 required extracorporeal membrane oxygenation. Nine patients (7 adults and 2 children) died. CONCLUSIONS: This study demonstrates that (1) more than 30% of patients with IEI had mild coronavirus disease 2019 (COVID-19) and (2) risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients with IEI, including more younger patients. Further studies will identify pathways that are associated with increased risk of severe disease and are nonredundant or redundant for protection against SARS-CoV-2. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:147 issue:2 pages:520-531 ispartof: location:United States status: published

Published
2021

8. Consensus of the Italian Primary Immunodeficiency Network on transition management from pediatric to adult care in patients affected with childhood-onset inborn errors of immunity

Author

Baldassarre Martire, Luciana Chessa, Alessandro Plebani, Francesca Conti, Andrea Finocchi, Francesca Ferrua, Laura Dotta, Clementina Canessa, Vassilios Lougaris, Donato Amodio, Emilia Cirillo, Davide Montin, Federica Barzaghi, Franco Locatelli, Alberto Tommasini, Viviana Moschese, Maria Pia Cicalese, Rosa Maria Dellepiane, Andrea Pession, Chiara Azzari, Lucia Augusta Baselli, Caterina Cancrini, Maria Caterina Putti, Raffaele Badolato, Alessandro Aiuti, Claudio Pignata, Annarosa Soresina, Roberta Romano, Silvia Ricci, Agata Polizzi, Antonio Marzollo, Giuliana Giardino, Cirillo, E., Giardino, G., Ricci, S., Moschese, V., Lougaris, V., Conti, F., Azzari, C., Barzaghi, F., Canessa, C., Martire, B., Badolato, R., Dotta, L., Soresina, A., Cancrini, C., Finocchi, A., Montin, D., Romano, R., Amodio, D., Ferrua, F., Tommasini, A., Baselli, L. A., Dellepiane, R. M., Polizzi, A., Chessa, L., Marzollo, A., Cicalese, M. P., Putti, M. C., Pession, A., Aiuti, A., Locatelli, F., Plebani, A., Pignata, C., Cirillo, Emilia, Giardino, Giuliana, Ricci, Silvia, Moschese, Viviana, Lougaris, Vassilio, Conti, Francesca, Azzari, Chiara, Barzaghi, Federica, Canessa, Clementina, Martire, Baldassarre, Badolato, Raffaele, Dotta, Laura, Soresina, Annarosa, Cancrini, Caterina, Finocchi, Andrea, Montin, Davide, Romano, Roberta, Amodio, Antonio, Ferrua, Francesca, Tommasini, Alberto, Baselli, Lucia Augusta, Dellepiane, Rosa Maria, Polizzi, Agata, Chessa, Luciana, Marzollo, Antonio, Cicalese, Mariapia, Putti, Maria Caterina, Pession, Andrea, Aiuti, Alessandro, Locatelli, Franco, Plebani, Alessandro, and Pignata, Claudio

Subjects
0301 basic medicine, Stress management, DiGeorge syndrome, Italian Network of Primary Immunodeficiencies, Transitional care, combined immunodeficiency, dna-repai syndromes, humoral immune defects, inborn errors of immunity, innate immune defects, primary immunodeficiency, DNA repair syndromes, 0302 clinical medicine, Italian Network of Primary Immunodeficiencie, Intellectual disability, Immunology and Allergy, Medicine, dna-repai syndrome, Age of Onset, Child, Settore MED/38, Italy, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Practice Guidelines as Topic, Adult, medicine.medical_specialty, Transition to Adult Care, Consensus, Genetic counseling, Primary Immunodeficiency Diseases, Immunology, humoral immune defect, 03 medical and health sciences, Quality of life (healthcare), Humans, Information Services, business.industry, Common variable immunodeficiency, medicine.disease, DNA repair syndrome, 030104 developmental biology, Family medicine, Primary immunodeficiency, Age of onset, business, innate immune defect, 030217 neurology & neurosurgery
Abstract

Medical advances have dramatically improved the long-term prognosis of children and adolescents with inborn errors of immunity (IEIs). Transfer of the medical care of individuals with pediatric IEIs to adult facilities is also a complex task because of the large number of distinct disorders, which requires involvement of patients and both pediatric and adult care providers. To date, there is no consensus on the optimal pathway of the transitional care process and no specific data are available in the literature regarding patients with IEIs. We aimed to develop a consensus statement on the transition process to adult health care services for patients with IEIs. Physicians from major Italian Primary Immunodeficiency Network centers formulated and answered questions after examining the currently published literature on the transition from childhood to adulthood. The authors voted on each recommendation. The most frequent IEIs sharing common main clinical problems requiring full attention during the transitional phase were categorized into different groups of clinically related disorders. For each group of clinically related disorders, physicians from major Italian Primary Immunodeficiency Network institutions focused on selected clinical issues representing the clinical hallmark during early adulthood.

Published
2020

9. The Italian Registry for Primary Immunodeficiencies (Italian Primary Immunodeficiency Network; IPINet): Twenty Years of Experience (1999–2019)

Author

A G Ugazio, Giovanna Russo, Maria Giovanna Danieli, Alberto Tommasini, Maria Cristina Pietrogrande, Raffaele Badolato, Andrea Pession, Carlo Agostini, Fabio Cardinale, Eleonora Gambineri, Baldassare Martire, Adele Civino, Manuela Baronio, Marco Gattorno, Marco Zecca, Viviana Moschese, Chiara Azzari, Alessio Benvenuto, Marzia Duse, Antonino Trizzino, Luisa Gazzurelli, Isabella Quinti, Vassilios Lougaris, Andrea Matucci, Giuseppe Spadaro, Claudio Lunardi, Angelo Vacca, Roberto Rondelli, Maria Caterina Putti, Luciana Chessa, Giovanna Fabio, Andrea Biondi, Fausto Cossu, Roberto Paganelli, Paolo Rossi, Rita Consolini, Alessandro Aiuti, Gian Luigi Marseglia, Luigi Carpino, Caterina Cancrini, Maddalena Marinoni, Silvana Martino, Claudio Pignata, Annarosa Soresina, Patrizia Bertolini, Alessandro Plebani, Lougaris, V., Pession, A., Baronio, M., Soresina, A., Rondelli, R., Gazzurelli, L., Benvenuto, A., Martino, S., Gattorno, M., Biondi, A., Zecca, M., Marinoni, M., Fabio, G., Aiuti, A., Marseglia, G., Putti, M. C., Agostini, C., Lunardi, C., Tommasini, A., Bertolini, P., Gambineri, E., Consolini, R., Matucci, A., Azzari, C., Danieli, M. G., Paganelli, R., Duse, M., Cancrini, C., Moschese, V., Chessa, L., Spadaro, G., Civino, A., Vacca, A., Cardinale, F., Martire, B., Carpino, L., Trizzino, A., Russo, G., Cossu, F., Badolato, R., Pietrogrande, M. C., Quinti, I., Rossi, P., Ugazio, A., Pignata, C., Plebani, A., Lougaris, V, Pession, A, Baronio, M, Soresina, A, Rondelli, R, Gazzurelli, L, Benvenuto, A, Martino, S, Gattorno, M, Biondi, A, Zecca, M, Marinoni, M, Fabio, G, Aiuti, A, Marseglia, G, Putti, M, Agostini, C, Lunardi, C, Tommasini, A, Bertolini, P, Gambineri, E, Consolini, R, Matucci, A, Azzari, C, Danieli, M, Paganelli, R, Duse, M, Cancrini, C, Moschese, V, Chessa, L, Spadaro, G, Civino, A, Vacca, A, Cardinale, F, Martire, B, Carpino, L, Trizzino, A, Russo, G, Cossu, F, Badolato, R, Pietrogrande, M, Quinti, I, Rossi, P, Ugazio, A, Pignata, C, and Plebani, A

Subjects
Adult, Male, medicine.medical_specialty, Pediatrics, Primary immunodeficiencies, Adolescent, Databases, Factual, Primary Immunodeficiency Diseases, Immunology, Age at diagnosis, History, 21st Century, Combined immunodeficiencies, Young Adult, Medical microbiology, patient registry, Epidemiology, medicine, Prevalence, Immunology and Allergy, Humans, Registries, Geography, Medical, Child, Adult patients, business.industry, Infant, Newborn, Infant, History, 20th Century, medicine.disease, Prognosis, Settore MED/38, Natural history, Italy, Child, Preschool, Population Surveillance, Cohort, Primary immunodeficiency, Original Article, Female, business
Abstract

Primary immunodeficiencies (PIDs) are heterogeneous disorders, characterized by variable clinical and immunological features. National PID registries offer useful insights on the epidemiology, diagnosis, and natural history of these disorders. In 1999, the Italian network for primary immunodeficiencies (IPINet) was established. We report on data collected from the IPINet registry after 20 years of activity. A total of 3352 pediatric and adult patients affected with PIDs are registered in the database. In Italy, a regional distribution trend of PID diagnosis was observed. Based on the updated IUIS classification of 2019, PID distribution in Italy showed that predominantly antibody deficiencies account for the majority of cases (63%), followed by combined immunodeficiencies with associated or syndromic features (22.5%). The overall age at diagnosis was younger for male patients. The minimal prevalence of PIDs in Italy resulted in 5.1 per 100.000 habitants. Mortality was similar to other European registries (4.2%). Immunoglobulin replacement treatment was prescribed to less than one third of the patient cohort. Collectively, this is the first comprehensive description of the PID epidemiology in Italy.

Published
2020

10. Consensus statement of the Italian society of pediatric allergy and immunology for the pragmatic management of children and adolescents with allergic or immunological diseases during the COVID-19 pandemic

Author

Fabio Cardinale, Giorgio Ciprandi, Salvatore Barberi, Roberto Bernardini, Carlo Caffarelli, Mauro Calvani, Giovanni Cavagni, Elena Galli, Domenico Minasi, Michele Miraglia Del Giudice, Viviana Moschese, Elio Novembre, Francesco Paravati, Diego G Peroni, Maria Angela Tosca, Giovanni Traina, Salvatore Tripodi, Gian Luigi Marseglia, Doriana Amato, Caterina Anania, Elisa Anastasio, Rachele Antignani, Stefania Arasi, Martire Baldassarre, Ermanno Baldo, Andrea Barbalace, Simona Barni, Federica Betti, Annamaria Bianchi, Ezio Bolzacchini, Maira Bonini, Paolo Bottau, Sara Bozzetto, Maria Antonia Brighetti, Davide Caimmi, Silvia Caimmi, Luigi Calzone, Caterina Cancrini, Lucia Caminiti, Giulia Capata, Lucetta Capra, Carlo Capristo, Elena Carboni, Francesco Carella, Riccardo Castagnoli, Elena Chiappini, Fernanda Chiera, Iolanda Chinellato, Loredana Chini, Francesca Cipriani, Flavio Civitelli, Pasquale Comberiati, Daniele Contini, Stefania Corrente, Claudio Cravidi, Giuseppe Crisafulli, Barbara Cuomo, Enza D'Auria, Sofia D'Elios, Fabio Decimo, Auro Della Giustina, Rosa Maria Delle Piane, Maria De Filippo, Valentina De Vittori, Lucia Diaferio, Maria Elisa Di Cicco, Dora Di Mauro, Marzia Duse, Silvia Federici, Giuseppe Felice, Maria Grazia Fenu, Giuliana Ferrante, Tiziana Foti, Fabrizio Franceschini, Daniele Ghiglioni, Giuliana Giardino, Mattia Giovannini, Giovanni Cosimo Indirli, Cristiana Indolfi, Massimo Landi, Francesco La Torre, Lucia Maddalena Leone, Amelia Licari, Lucia Liotti, Vassilios Lougaris, Nunzia Maiello, Paride Mantecca, Sara Manti, Marco Maria Mariani, Alberto Martelli, Carla Mastrorilli, Violetta Mastrorilli, Davide Montin, Francesca Mori, Roberta Olcese, Giorgio Ottaviano, Claudia Paglialunga, Giovanni Pajno, Giuseppe Parisi, Stefano Pattini, Luca Pecoraro, Umberto Pelosi, Claudio Pignata, Giampaolo Ricci, Silvia Ricci, Stefano Rizzi, Caterina Rizzo, Sara Rosati, Paolo Rosso, Maria Sangerardi, Angelica Santoro, Francesca Saretta, Lucrezia Sarti, Marco Sartorio, Majla Sgruletti, Annarosa Soresina, Ifigenia Sfika, Mayla Sgrulletti, Nuccia Tesse, Valentina Tranchino, Alessandro Travaglini, Malizia Velia, Elvira Verduci, Mario Vernich, Elisabetta Veronelli, Stefano Volpi, Martina Votto, Anna Maria Zicari, Cardinale, F., Ciprandi, G., Barberi, S., Bernardini, R., Caffarelli, C., Calvani, M., Cavagni, G., Galli, E., Minasi, D., Del Giudice, M. M., Moschese, V., Novembre, E., Paravati, F., Peroni, D. G., Tosca, M. A., Traina, G., Tripodi, S., Marseglia, G. L., Amato, D., Anania, C., Anastasio, E., Antignani, R., Arasi, S., Baldassarre, M., Baldo, E., Barbalace, A., Barni, S., Betti, F., Bianchi, A., Bolzacchini, E., Bonini, M., Bottau, P., Bozzetto, S., Brighetti, M. A., Caimmi, D., Caimmi, S., Calzone, L., Cancrini, C., Caminiti, L., Capata, G., Capra, L., Capristo, C., Carboni, E., Carella, F., Castagnoli, R., Chiappini, E., Chiera, F., Chinellato, I., Chini, L., Cipriani, F., Civitelli, F., Comberiati, P., Contini, D., Corrente, S., Cravidi, C., Crisafulli, G., Cuomo, B., D'Auria, E., D'Elios, S., Decimo, F., Giustina, A. D., Piane, R. M. D., De Filippo, M., De Vittori, V., Diaferio, L., Di Mauro, M. E., Duse, M., Federici, S., Felice, G., Fenu, G., Ferrante, G., Foti, T., Franceschini, F., Ghiglioni, D., Giardino, G., Giovannini, M., Indirli, G. C., Indolfi, C., Landi, M., La Torre, F., Leone, L. M., Licari, A., Liotti, L., Lougaris, V., Maiello, N., Mantecca, P., Manti, S., Mariani, M. M., Martelli, A., Mastrorilli, C., Mastrorilli, V., Montin, D., Mori, F., Olcese, R., Ottaviano, G., Paglialunga, C., Pajno, G., Parisi, G., Pattini, S., Pecoraro, L., Pelosi, U., Pignata, C., Ricci, G., Ricci, S., Rizzi, S., Rizzo, C., Rosati, S., Rosso, P., Sangerardi, M., Santoro, A., Saretta, F., Sarti, L., Sartorio, M., Sgruletti, M., Soresina, A., Sfika, I., Sgrulletti, M., Tesse, N., Tranchino, V., Travaglini, A., Velia, M., Verduci, E., Vernich, M., Veronelli, E., Volpi, S., Votto, M., Zicari, A. M., Cardinale, Fabio, Ciprandi, Giorgio, Barberi, Salvatore, Bernardini, Roberto, Caffarelli, Carlo, Calvani, Mauro, Cavagni, Giovanni, Galli, Elena, Minasi, Domenico, Del Giudice, Michele Miraglia, Moschese, Viviana, Novembre, Elio, Paravati, Francesco, Peroni, Diego G, Tosca, Maria Angela, Traina, Giovanni, Tripodi, Salvatore, Marseglia, Gian Luigi, SIAIP task force Pignata, Claudio, Cardinale, F, Ciprandi, G, Barberi, S, Bernardini, R, Caffarelli, C, Calvani, M, Cavagni, G, Galli, E, Minasi, D, Del Giudice, M, Moschese, V, Novembre, E, Paravati, F, Peroni, D, Tosca, M, Traina, G, Tripodi, S, Marseglia, G, Amato, D, Anania, C, Anastasio, E, Antignani, R, Arasi, S, Baldassarre, M, Baldo, E, Barbalace, A, Barni, S, Betti, F, Bianchi, A, Bolzacchini, E, Bonini, M, Bottau, P, Bozzetto, S, Brighetti, M, Caimmi, D, Caimmi, S, Calzone, L, Cancrini, C, Caminiti, L, Capata, G, Capra, L, Capristo, C, Carboni, E, Carella, F, Castagnoli, R, Chiappini, E, Chiera, F, Chinellato, I, Chini, L, Cipriani, F, Civitelli, F, Comberiati, P, Contini, D, Corrente, S, Cravidi, C, Crisafulli, G, Cuomo, B, D'Auria, E, D'Elios, S, Decimo, F, Giustina, A, Piane, R, De Filippo, M, De Vittori, V, Diaferio, L, Di Mauro, M, Duse, M, Federici, S, Felice, G, Fenu, G, Ferrante, G, Foti, T, Franceschini, F, Ghiglioni, D, Giardino, G, Giovannini, M, Indirli, G, Indolfi, C, Landi, M, La Torre, F, Leone, L, Licari, A, Liotti, L, Lougaris, V, Maiello, N, Mantecca, P, Manti, S, Mariani, M, Martelli, A, Mastrorilli, C, Mastrorilli, V, Montin, D, Mori, F, Olcese, R, Ottaviano, G, Paglialunga, C, Pajno, G, Parisi, G, Pattini, S, Pecoraro, L, Pelosi, U, Pignata, C, Ricci, G, Ricci, S, Rizzi, S, Rizzo, C, Rosati, S, Rosso, P, Sangerardi, M, Santoro, A, Saretta, F, Sarti, L, Sartorio, M, Sgruletti, M, Soresina, A, Sfika, I, Sgrulletti, M, Tesse, N, Tranchino, V, Travaglini, A, Velia, M, Verduci, E, Vernich, M, Veronelli, E, Volpi, S, Votto, M, Zicari, A, and Fabio Cardinale, Giorgio Ciprandi, Salvatore Barberi, Roberto Bernardini, Carlo Caffarelli, Mauro Calvani, Giovanni Cavagni, Elena Galli, Domenico Minasi, Michele Miraglia Del Giudice, Viviana Moschese, Elio Novembre, Francesco Paravati, Diego G Peroni, Maria Angela Tosca, Giovanni Traina, Salvatore Tripodi, Gian Luigi Marseglia, Doriana Amato, Caterina Anania, Elisa Anastasio, Rachele Antignani, Stefania Arasi, Martire Baldassarre, Ermanno Baldo, Andrea Barbalace, Simona Barni, Federica Betti, Annamaria Bianchi, Ezio Bolzacchini, Maira Bonini, Paolo Bottau, Sara Bozzetto, Maria Antonia Brighetti, Davide Caimmi, Silvia Caimmi, Luigi Calzone, Caterina Cancrini, Lucia Caminiti, Giulia Capata, Lucetta Capra, Carlo Capristo, Elena Carboni, Francesco Carella, Riccardo Castagnoli, Elena Chiappini, Fernanda Chiera, Iolanda Chinellato, Loredana Chini, Francesca Cipriani, Flavio Civitelli, Pasquale Comberiati, Daniele Contini, Stefania Corrente, Claudio Cravidi, Giuseppe Crisafulli, Barbara Cuomo, Enza D'Auria, Sofia D'Elios, Fabio Decimo, Auro Della Giustina, Rosa Maria Delle Piane, Maria De Filippo, Valentina De Vittori, Lucia Diaferio, Maria Elisa Di Cicco, Dora Di Mauro, Marzia Duse, Silvia Federici, Giuseppe Felice, Maria Grazia Fenu, Giuliana Ferrante, Tiziana Foti, Fabrizio Franceschini, Daniele Ghiglioni, Giuliana Giardino, Mattia Giovannini, Giovanni Cosimo Indirli, Cristiana Indolfi, Massimo Landi, Francesco La Torre, Lucia Maddalena Leone, Amelia Licari, Lucia Liotti, Vassilios Lougaris, Nunzia Maiello, Paride Mantecca, Sara Manti, Marco Maria Mariani, Alberto Martelli, Carla Mastrorilli, Violetta Mastrorilli, Davide Montin, Francesca Mori, Roberta Olcese, Giorgio Ottaviano, Claudia Paglialunga, Giovanni Pajno, Giuseppe Parisi, Stefano Pattini, Luca Pecoraro, Umberto Pelosi, Claudio Pignata, Giampaolo Ricci, Silvia Ricci, Stefano Rizzi, Caterina Rizzo, Sara Rosati, Paolo Rosso, Maria Sangerardi, Angelica Santoro, Francesca Saretta, Lucrezia Sarti, Marco Sartorio, Majla Sgruletti, Annarosa Soresina, Ifigenia Sfika, Mayla Sgrulletti, Nuccia Tesse, Valentina Tranchino, Alessandro Travaglini, Malizia Velia, Elvira Verduci, Mario Vernich, Elisabetta Veronelli, Stefano Volpi, Martina Votto, Anna Maria Zicari

Subjects
Allergy, Review, 030207 dermatology & venereal diseases, Settore MED/38 - Pediatria Generale E Specialistica, 0302 clinical medicine, COVID-19, Child, Pandemic, Immunologic disease, Asthma, Adolescent, Viral, 030212 general & internal medicine, Disease management (health), Societies, Medical, pandemic, child, adolescent, allergy, asthma, immunologic disease, Incidence (epidemiology), lcsh:RJ1-570, Disease Management, General Medicine, Atopic dermatitis, Settore MED/38, Coronavirus Infections, Decision Making, Humans, Italy, Pneumonia, Viral, Pragmatic Clinical Trials as Topic, SARS-CoV-2, Allergy and Immunology, Betacoronavirus, Consensus, Pandemics, Latex allergy, Human, Telemedicine, Consensu, 03 medical and health sciences, Medical, medicine, Risk factor, Betacoronaviru, business.industry, Coronavirus Infection, lcsh:Pediatrics, Pneumonia, medicine.disease, Immunology, Societies, business, Rare disease
Abstract

The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic.Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases.

Published
2020

11. Imaging of bronchial pathology in antibody deficiency

Author

Cinzia Milito, Maria Pia Bondioni, Scott Hackett, Esther de Vries, Alessandro Plebani, Vassilios Lougaris, Nicholas Screaton, Isabelle Meyts, Goffredo Serra, Nermeen Galal, Jamanda Haddock, M Lucas, Arpan K. Banerjee, Michael R. Loebinger, Vojtech Thon, Katharina Schütz, Peter M. van Hagen, Alison M. Condliffe, Robert G Stirling, Bodo Grimbacher, Annarosa Soresina, Luis Ignacio Gonzalez-Granado, John R. Hurst, Gertjan J. Driessen, Klaus Warnatz, Vera Postranecka, Peter Kelleher, Jiri Litzman, Dinakantha S. Kumararatne, Andrew Exley, Isabella Quinti, Judith Babar, Cesare Sirignano, Smita Y. Patel, Ieneke Hartmann, Ulrich Baumann, Giuseppe Spadaro, Francesco Fraioli, Sabine Dettmer, Alison Jones, Annemarie Bruining, Helen Chapel, Milica Mitrevski, Claire-Michèle Farber, Benjamin Gathmann, Diana Alecsandru, Schütz, Katharina, Alecsandru, Diana, Grimbacher, Bodo, Haddock, Jamanda, Bruining, Annemarie, Driessen, Gertjan, de Vries, Esther, van Hagen, Peter M., Hartmann, Ieneke, Fraioli, Francesco, Milito, Cinzia, Mitrevski, Milica, Quinti, Isabella, Serra, Goffredo, Kelleher, Peter, Loebinger, Michael, Litzman, Jiri, Postranecka, Vera, Thon, Vojtech, Babar, Judith, Condliffe, Alison M., Exley, Andrew, Kumararatne, Dinakantha, Screaton, Nick, Jones, Alison, Bondioni, Maria P., Lougaris, Vassilio, Plebani, Alessandro, Soresina, Annarosa, Sirignano, Cesare, Spadaro, Giuseppe, Galal, Nermeen, Gonzalez-Granado, Luis I., Dettmer, Sabine, Stirling, Robert, Chapel, Helen, Lucas, Mary, Patel, Smita, Farber, Claire-Michele, Meyts, Isabelle, Banerjee, Arpan K., Hackett, Scott, Hurst, John R., Warnatz, Klau, Gathmann, Benjamin, Baumann, Ulrich, Pediatrics, Public Health, Immunology, Internal Medicine, Radiology & Nuclear Medicine, Tranzo, Scientific center for care and wellbeing, and Geestelijke Gezondheidszorg

Subjects
Male, 0301 basic medicine, Pathology, bronchiectasis, X-linked agammaglobulinemia, LARGE COHORT, Disease, Pulmonary function testing, bronchiectasi, 0302 clinical medicine, Medical microbiology, Immunology and Allergy, Child, Immunodeficiency, medicine.diagnostic_test, CVID, X-LINKED AGAMMAGLOBULINEMIA, 3. Good health, LUNG-FUNCTION, 1107 Immunology, Child, Preschool, DISEASES, Female, Life Sciences & Biomedicine, Adult, Spirometry, medicine.medical_specialty, Adolescent, Immunology, CYSTIC FIBROSIS BRONCHIECTASIS, Bronchi, COMMON VARIABLE IMMUNODEFICIENCY, Chest CT in Antibody Deficiency Group, Young Adult, 03 medical and health sciences, Chest CT, bronchial pathology, primary antibody deficiency, medicine, MANAGEMENT, Humans, COMPUTED-TOMOGRAPHY, Thoracic Wall, Aged, Science & Technology, Bronchiectasis, business.industry, Common variable immunodeficiency, Immunologic Deficiency Syndromes, Infant, PULMONARY-FUNCTION, medicine.disease, 030104 developmental biology, Tomography, X-Ray Computed, business, SCAN, 030215 immunology
Abstract

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease.

Published
2019

12. Pathogenesis of Autoimmune Cytopenias in Inborn Errors of Immunity Revealing Novel Therapeutic Targets

Author

Manuela Cortesi, Annarosa Soresina, Laura Dotta, Chiara Gorio, Marco Cattalini, Vassilios Lougaris, Fulvio Porta, and Raffaele Badolato

Subjects
inborn errors of immunity (IEI), Purpura, Thrombocytopenic, Idiopathic, target therapy, Immunology, Autoimmunity, Anemia, Idiopathic, gene therapy, Thrombocytopenia, autoimmune cytopenias, genetic disorders, Child, Humans, Anemia, Hemolytic, Autoimmune, Thrombocytopenic, hemic and lymphatic diseases, Immunology and Allergy, Hemolytic, Purpura, Autoimmune
Abstract

Autoimmune diseases are usually associated with environmental triggers and genetic predisposition. However, a few number of autoimmune diseases has a monogenic cause, mostly in children. These diseases may be the expression, isolated or associated with other symptoms, of an underlying inborn error of immunity (IEI). Autoimmune cytopenias (AICs), including immune thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), autoimmune neutropenia (AN), and Evans’ syndrome (ES) are common presentations of immunological diseases in the pediatric age, with at least 65% of cases of ES genetically determined. Autoimmune cytopenias in IEI have often a more severe, chronic, and relapsing course. Treatment refractoriness also characterizes autoimmune cytopenia with a monogenic cause, such as IEI. The mechanisms underlying autoimmune cytopenias in IEI include cellular or humoral autoimmunity, immune dysregulation in cases of hemophagocytosis or lymphoproliferation with or without splenic sequestration, bone marrow failure, myelodysplasia, or secondary myelosuppression. Genetic characterization of autoimmune cytopenias is of fundamental importance as an early diagnosis improves the outcome and allows the setting up of a targeted therapy, such as CTLA-4 IgG fusion protein (Abatacept), small molecule inhibitors (JAK-inhibitors), or gene therapy. Currently, gene therapy represents one of the most attractive targeted therapeutic approaches to treat selected inborn errors of immunity. Even in the absence of specific targeted therapies, however, whole exome genetic testing (WES) for children with chronic multilineage cytopenias should be considered as an early diagnostic tool for disease diagnosis and genetic counseling.

Published
2022

13. Inherited defects in the complement system

Author

Leonardi, L, La Torre, F, Soresina, A, Federici, S, Cancrini, C, Castagnoli, R, Cinicola, B, Corrente, S, Giardino, G, Lougaris, V, Volpi, S, Marseglia, G, Cardinale, F, and Immunology Task Force of the Italian Society of Pediatric Allergy and Immunology (SIAIP)

Subjects
Immunology, pathways, alternative, classical, complement, deficiency, inherited, lectin, system, Complement System Proteins, Settore MED/02, Pediatrics, Perinatology and Child Health, Humans, Immunology and Allergy
Abstract

The complement system plays an essential role in both innate and adaptive immune responses. Any dysregulation in this system can disturb normal host defense and alter inflammatory response leading to both infections and autoimmune diseases. The complement system can be activated through three different pathways. Inherited complement deficiencies have been described for all complement components and their regulators. Despite being rare diseases, complement deficiencies are often severe, with a frequent onset during childhood. We provide an overview of clinical disorders related to these disorders and describe current diagnostic strategies required for their comprehensive characterization and management.

Published
2022

14. Health-Related Quality of Life and Emotional Difficulties in Chronic Granulomatous Disease: Data on Adult and Pediatric Patients from Italian Network for Primary Immunodeficiency (IPINet)

Author

Maria Carrabba, Baldassarre Martire, Andrea Finocchi, Samuele Naviglio, Marco De Carli, Antonino Trizzino, Isabella Quinti, Emilia Cirillo, Annarosa Soresina, Marco Gattorno, Maria Sangerardi, Alessandro Plebani, Franco Locatelli, Alessandro Aiuti, Federica Pulvirenti, Alice Bertaina, Maria Grazia Foschino Barbaro, Claudio Pignata, Maddalena Migliavacca, Pulvirenti, F., Sangerardi, M., Plebani, A., Soresina, A., Finocchi, A., Pignata, C., Cirillo, E., Trizzino, A., Aiuti, A., Migliavacca, M., Locatelli, F., Bertaina, A., Naviglio, S., Carrabba, M., De Carli, M., Barbaro, M. G. F., Gattorno, M., Quinti, I., and Martire, B.

Subjects
Male, Pediatrics, medicine.medical_treatment, burden of disease, chronic granulomatous disease, emotional difficulties, health-related quality of life, hematopoietic stem cell transplantation, PEDsQL, SDQ, SF-12, Hematopoietic stem cell transplantation, Chronic granulomatous disease, Granulomatous Disease, Chronic, Psychological Distress, Severity of Illness Index, Medical microbiology, Quality of life, hemic and lymphatic diseases, Immunology and Allergy, Registries, emotional difficultie, Child, Middle Aged, Settore MED/38, Caregivers, Italy, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Child, Preschool, Female, Psychosocial, Adult, medicine.medical_specialty, Adolescent, Immunology, Cholestyramine Resin, Young Adult, Internal medicine, Diabetes mellitus, medicine, Humans, business.industry, Immunologic Deficiency Syndromes, medicine.disease, Rheumatology, Primary immunodeficiency, Quality of Life, business
Abstract

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by life-threatening infections, inflammation, and autoimmunity with an impact on health-related quality of life (HRQoL). Few data are available for children, whereas no study has been conducted in adults. Here, we investigated HRQoL and emotional functioning of 19 children and 28 adults enrolled in Italian registry for CGD. PEDsQL and SDQ were used for children and their caregivers, and adults completed the SF-12 questionnaire. Mean scores were compared with norms and with patients affected by chronic diseases. Comparisons were made for CGD patients who underwent or not hematopoietic stem cell transplantation (HSCT). When compared with norms, CGD children exhibited higher difficulties in social/school areas, peer relationship, and conduct/emotional problems (

Published
2020

15. Immunological basis of virus-host interaction in COVID-19

Author

La Torre, F, Leonardi, L, Giardino, G, Volpi, S, Federici, S, Soresina, A, Cancrini, C, Lougaris, V, Castagnoli, R, Corrente, S, Cardinale, F, Immunology Commission of the Italian Society of Pediatric Allergy, I, La Torre, F., Leonardi, L., Giardino, G., Volpi, S., Federici, S., Soresina, A., Cancrini, C., Lougaris, V., Castagnoli, R., Corrente, S., and Cardinale, F.

Subjects
Coronavirus disease 2019 (COVID-19), Immunology, Inflammation, Virus-host interaction, Covid‐19 in Children and Adolescents, 03 medical and health sciences, 2020 Update from The Italian Society of Pediatric Allergy and Immunology, 0302 clinical medicine, Immune system, Host Microbial Interaction, children, COVID‐19, Medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Pediatrics, Perinatology, and Child Health, Host Microbial Interactions, Kawasaki disease, business.industry, SARS-CoV-2, COVID-19, cytokine storm, immunopathogenesis, Cytokine Release Syndrome, Pneumonia, medicine.disease, Cytokine release syndrome, Settore MED/02, 030228 respiratory system, immunopathogenesi, Pediatrics, Perinatology and Child Health, Etiology, Supplement Article, Viral disease, medicine.symptom, business, Cytokine storm, Human
Abstract

COVID‐19 is a complex new viral disease, in which a strict balance between anti‐viral immune response and the ensuing organ inflammation has a critical role in determining the clinical course. In adults, compelling evidence exists indicating that an uncontrolled inflammatory response ("cytokine storm") is pivotal in determining disease progression and mortality. Children may rarely present with severe disease. Modulating factors related to the host's genetic factors, age‐related susceptibility, and the capability to mount appropriate immune responses might play a role in control virus load at an early stage and regulating the inflammatory reaction. Elucidating these mechanisms seems crucial in developing target therapies according to patient's age, immunologic status, and disease evolution in COVID‐19.

Published
2020

16. Long-term follow-up of 168 patients with X-linked agammaglobulinemia reveals increased morbidity and mortality

Author

Ludovica Crescenzi, Emilia Cirillo, Alessio Benvenuto, Fabio Cardinale, Andrea Pession, Federica Pulvirenti, Simona Ferrari, Maria Caterina Putti, Giovanna Fabio, Rita Consolini, Fausto Cossu, Andrea Finocchi, Stefano Volpi, Angelo Vacca, Carolina Marasco, Marco Zecca, Claudio Pignata, Viviana Moschese, Gigliola Di Matteo, Lucia Leonardi, Raffaele Badolato, Marzia Duse, A G Ugazio, Manuela Baronio, Maddalena Marinoni, Chiara Azzari, Sara Signa, Silvana Martino, Maria Licciardello, Rosa Maria Dellepiane, Lucia Augusta Baselli, Luisa Gazzurelli, Giuseppe Spadaro, Claudio Lunardi, Cinzia Milito, Baldassare Martire, Alessandro Plebani, Francesca Conti, Caterina Cancrini, Maria Carrabba, Patrizia Bertolini, Francesco Cinetto, Davide Montin, Antonino Trizzino, Isabella Quinti, Vassilios Lougaris, Annarosa Soresina, Silvia Ricci, Silvia Giliani, Lougaris, V., Soresina, A., Baronio, M., Montin, D., Martino, S., Signa, S., Volpi, S., Zecca, M., Marinoni, M., Baselli, L. A., Dellepiane, R. M., Carrabba, M., Fabio, G., Putti, M. C., Cinetto, F., Lunardi, C., Gazzurelli, L., Benvenuto, A., Bertolini, P., Conti, F., Consolini, R., Ricci, S., Azzari, C., Leonardi, L., Duse, M., Pulvirenti, F., Milito, C., Quinti, I., Cancrini, C., Finocchi, A., Moschese, V., Cirillo, E., Crescenzi, L., Spadaro, G., Marasco, C., Vacca, A., Cardinale, F., Martire, B., Trizzino, A., Licciardello, M., Cossu, F., Di Matteo, G., Badolato, R., Ferrari, S., Giliani, S., Pession, A., Ugazio, A., Pignata, C., and Plebani, A.

Subjects
Lung Diseases, Male, 0301 basic medicine, Pediatrics, X-linked agammaglobulinemia, Bruton tyrosine kinase, 0302 clinical medicine, Bruton’s tyrosin kinase, Agammaglobulinemia, Immunology and Allergy, Medicine, Child, biology, Incidence (epidemiology), Chronic sinusitis, Genetic Diseases, X-Linked, Middle Aged, Settore MED/38, Natural history, Italy, chronic lung disease, Genetic Diseases, Child, Preschool, Adolescent, Adult, Follow-Up Studies, Humans, Infant, Infant, Newborn, Infections, Sinusitis, Survival Analysis, Young Adult, Antibody, medicine.medical_specialty, Long term follow up, Immunology, 03 medical and health sciences, Preschool, business.industry, X-Linked, Newborn, medicine.disease, 030104 developmental biology, Lung disease, Primary immunodeficiency, biology.protein, business, 030215 immunology
Abstract

Background X-linked agammaglobulinemia (XLA) is the prototype of primary humoral immunodeficiencies. Long-term follow-up studies regarding disease-related complications and outcome are scarce. Objective Our aim was to describe the natural history of XLA. Methods A nationwide multicenter study based on the Italian Primary Immunodeficiency Network registry was established in 2000 in Italy. Affected patients were enrolled by documenting centers, and the patients' laboratory, clinical, and imaging data were recorded on an annual base. Results Data on the patients (N = 168) were derived from a cumulative follow-up of 1370 patient-years, with a mean follow-up of 8.35 years per patient. The mean age at diagnosis decreased after establishment of the Italian Primary Immunodeficiency Network registry (84 months before vs 23 months after). Respiratory, skin, and gastrointestinal manifestations were the most frequent clinical symptoms at diagnosis and during long-term follow-up. Regular immunoglobulin replacement treatment reduced the incidence of invasive infections. Affected patients developed chronic lung disease over time (47% after 40 years of follow-up) in the presence of chronic sinusitis (84%). Malignancies were documented in a minority of cases (3.7%). Overall survival for affected patients was significantly reduced when compared with that for the healthy male Italian population, and it further deteriorated in the presence of chronic lung disease. Conclusions This is the first detailed long-term follow-up study for patients with XLA, revealing that although immunoglobulin replacement treatment reduces the incidence of invasive infections, it does not appear to influence the development of chronic lung disease. The overall survival of affected patients is reduced. Further studies are warranted to improve patients' clinical management and increase awareness among physicians.

Published
2020

17. Primary atopic disorders and chronic skin disease

Author

Cinicola, B, Corrente, S, Castagnoli, R, Lougaris, V, Giardino, G, Leonardi, L, Volpi, S, La Torre, F, Federici, S, Soresina, A, Cancrini, C, Marseglia, G, Cardinale, F, and Immunology Task Force of the Italian Society of Pediatric Allergy, I

Subjects
IgE, allergy, inborn errors of immunity, primary atopic disorders, skin, Hypersensitivity, Immediate, Immediate, Urticaria, Immunology, Eczema, Skin Diseases, Settore MED/02, Humans, Job Syndrome, Pediatrics, Perinatology and Child Health, Hypersensitivity, Immunology and Allergy
Abstract

Primary atopic disorders (PADs) are monogenic diseases characterized by allergy or atopy-related symptoms as fundamental features. In patients with PADs, primary immune deficiency and immune dysregulation symptoms are usually coexist. Chronic skin disease, manifesting with erythroderma, severe atopic dermatitis or eczema, and urticaria, is one of the main features observed in PADs, such as hyper-IgE syndromes, Omenn syndrome, Wiskott-Aldrich syndrome, IPEX-linked syndrome, skin barrier disorders, as well as some autoinflammatory diseases. The recognition of PADs in the context of an allergic phenotype is crucial to ensure prompt diagnosis and appropriate treatment. This article provides an overview of the main PADs with skin involvement.

Published
2021

18. Thymic epithelial cell alterations and defective thymopoiesis lead to central and peripheral tolerance perturbation in MHCII deficiency

Author

Francesca Ferrua, Ileana Bortolomai, Elena Fontana, Dario Di Silvestre, Rosita Rigoni, Genni Enza Marcovecchio, Elena Draghici, Francesca Brambilla, Maria Carmina Castiello, Gloria Delfanti, Despina Moshous, Capucine Picard, Tom Taghon, Victoria Bordon, Ansgar S. Schulz, Catharina Schuetz, Silvia Giliani, Annarosa Soresina, Andrew R. Gennery, Sara Signa, Blachy J. Dávila Saldaña, Ottavia M. Delmonte, Luigi D. Notarangelo, Chaim M. Roifman, Pietro Luigi Poliani, Paolo Uva, Pier Luigi Mauri, Anna Villa, and Marita Bosticardo

Subjects
Male, POSITIVE SELECTION, Proteome, T-Lymphocytes, Major histocompatibility complex, Epithelial cells, Inbred C57BL, T-Lymphocytes, Regulatory, DISEASE, Mice, thymus, Medicine and Health Sciences, Immunology and Allergy, Child, Immunodeficiency, Original Research, Mice, Knockout, central tolerance, MHCII, primary immunodeficiency, thymic epithelial cells, Adolescent, Animals, B-Lymphocytes, Case-Control Studies, Child, Preschool, Disease Models, Animal, Epithelial Cells, Europe, Female, Hematopoietic Stem Cell Transplantation, Histocompatibility Antigens Class II, Homeodomain Proteins, Humans, Infant, Mice, Inbred C57BL, North America, Severe Combined Immunodeficiency, Thymocytes, Thymus Gland, Transcriptome, Young Adult, Immune Tolerance, BARE LYMPHOCYTE SYNDROME, Bare lymphocyte syndrome, Peripheral tolerance, respiratory system, Regulatory, Thymus gland, medicine.anatomical_structure, DIFFERENTIATION, Severe combined immunodeficiency, B-CELLS, Central tolerance, CLASS-II DEFICIENCY, EXPRESSION, Knockout, ANTIGEN, Immunology, chemical and pharmacologic phenomena, Biology, Immune system, Immundefekt, medicine, REGULATORY T-CELLS, ddc:610, Preschool, B cell, Animal, RC581-607, medicine.disease, MICE, Disease Models, biology.protein, Primary immunodeficiency, Immunologic diseases. Allergy, MHC, DDC 610 / Medicine & health
Abstract

Major Histocompatibility Complex (MHC) class II (MHCII) deficiency (MHCII-D), also known as Bare Lymphocyte Syndrome (BLS), is a rare combined immunodeficiency due to mutations in genes regulating expression of MHCII molecules. MHCII deficiency results in impaired cellular and humoral immune responses, leading to severe infections and autoimmunity. Abnormal cross-talk with developing T cells due to the absence of MHCII expression likely leads to defects in thymic epithelial cells (TEC). However, the contribution of TEC alterations to the pathogenesis of this primary immunodeficiency has not been well characterized to date, in particular in regard to immune dysregulation. To this aim, we have performed an in-depth cellular and molecular characterization of TEC in this disease. We observed an overall perturbation of thymic structure and function in both MHCII−/− mice and patients. Transcriptomic and proteomic profiling of murine TEC revealed several alterations. In particular, we demonstrated that impairment of lymphostromal cross-talk in the thymus of MHCII−/− mice affects mTEC maturation and promiscuous gene expression and causes defects of central tolerance. Furthermore, we observed peripheral tolerance impairment, likely due to defective Treg cell generation and/or function and B cell tolerance breakdown. Overall, our findings reveal disease-specific TEC defects resulting in perturbation of central tolerance and limiting the potential benefits of hematopoietic stem cell transplantation in MHCII deficiency., publishedVersion

Published
2021

19. Clinical and Laboratory Features of 184 Italian Pediatric Patients Affected with Selective IgA Deficiency (SIgAD): a Longitudinal Single-Center Study

Author

Alba Pilotta, Vincenzo Villanacci, Giulio Gualdi, Elena Prandi, Giulia Ingrasciotta, Chiara Monfredini, Andrea Caravaggio, Laura Ruggeri, Annarosa Soresina, Vassilios Lougaris, Antonella Meini, Alessandro Plebani, Raffaele Badolato, Alberto Ravelli, Tiziana Lorenzini, Maurizio Fuoti, Barbara Felappi, Marco Cattalini, Antonella Fabiano, Livia Grazzani, A. Salpietro, Manuela Baronio, and Annamaria Sorlini

Subjects
Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Adolescent, Immunology, Population, Selective IgA deficiency, Cohort Studies, Atopy, 03 medical and health sciences, 0302 clinical medicine, Hypersensitivity, Humans, Immunology and Allergy, Medicine, Longitudinal Studies, Family history, Child, education, Respiratory Tract Infections, education.field_of_study, business.industry, Common variable immunodeficiency, Incidence (epidemiology), IgA Deficiency, common variable immunodeficiency, allergic manifestations, medicine.disease, celiac disease, pediatric, 030104 developmental biology, Italy, Child, Preschool, Cohort, Primary immunodeficiency, Female, business, 030215 immunology
Abstract

Selective IgA deficiency (SIgAD) is the most common humoral primary immunodeficiency. Long-term follow-up data in large cohort of pediatric patients are scarce. We report on a single-center cohort of 184 pediatric patients affected with selective IgA deficiency and describe the characteristics at diagnosis and during follow-up. Respiratory infections were the most common clinical finding leading to the initial diagnosis (62%). Positive family history for antibody deficiencies (selective IgA deficiency, common variable immunodeficiency) led to SIgAD diagnosis in 16% of cases. During follow-up, while the incidence of respiratory infections was not particularly high, gastrointestinal symptoms were reported in 27% of patients. Allergic manifestations were found in 23% at diagnosis and an additional 16% of patients during follow-up, leading to a prevalence of atopy of 39% among SIgAD patients. Autoimmune manifestations, excluding celiac disease, were found in 9% of affected patients during follow-up. Celiac disease was found in a high prevalence (14%). Increase of serum IgA levels to partial deficiency (9%) and normal serum levels for age (4%) was observed during follow-up. A small percentage of patients (2%) progressed to common variable immunodeficiency (CVID). In conclusion, this is the first study to describe a large single-center pediatric cohort of patients affected with SIgAD, revealing that overall most patients do well with regard to infections. Many develop CD, at a rate much higher than the general population. A few normalize their IgA levels. A few progress to CVID. Thus, careful follow-up is suggested to diagnose and treat potential complications earlier for avoiding potential morbidities.

Published
2019

20. Correction to: Imaging of Bronchial Pathology in Antibody Deficiency: Data from the European Chest CT Group

Author

Ieneke Hartmann, Goffredo Serra, Jamanda Haddock, Isabella Quinti, Scott Hackett, Diana Alecsandru, Annemarie Bruining, Katharina Schütz, Judith Babar, Alison Jones, Daniel Berthold, M Lucas, Giuseppe Spadaro, Ulrich Baumann, Vassilios Lougaris, Smita Y. Patel, Robert G Stirling, Annarosa Soresina, Nicholas Screaton, Helen Chapel, Claire Michele Farber, Nermeen Galal, Benjamin Gathmann, Arpan K. Banerjee, Dinakantha S. Kumararatne, Klaus Warnatz, Isabelle Meyts, Alison M. Condliffe, Milica Mitrevski, Peter Kelleher, Bodo Grimbacher, Cinzia Milito, Jiri Litzman, Esther de Vries, Vera Postranecka, Alessandro Plebani, Peter M. van Hagen, Vojtech Thon, John R. Hurst, Gertjan J. Driessen, Andrew Exley, Francesco Fraioli, Cesare Sirignano, Sabine Dettmer, Maria Pia Bondioni, Michael R. Loebinger, Jürgen Weidemann, Luis Ignacio Gonzalez-Granado, Schütz, Katharina, Alecsandru, Diana, Grimbacher, Bodo, Haddock, Jamanda, Bruining, Annemarie, Driessen, Gertjan, de Vries, Esther, M van Hagen, Peter, Hartmann, Ieneke, Fraioli, Francesco, Milito, Cinzia, Mitrevski, Milica, Quinti, Isabella, Serra, Goffredo, Kelleher, Peter, Loebinger, Michael, Litzman, Jiri, Postranecka, Vera, Thon, Vojtech, Babar, Judith, M Condliffe, Alison, Exley, Andrew, Kumararatne, Dinakantha, Screaton, Nick, Jones, Alison, P Bondioni, Maria, Lougaris, Vassilio, Plebani, Alessandro, Soresina, Annarosa, Sirignano, Cesare, Spadaro, Giuseppe, Galal, Nermeen, I Gonzalez-Granado, Lui, Dettmer, Sabine, Stirling, Robert, Chapel, Helen, Lucas, Mary, Patel, Smita, Farber, Claire-Michele, Meyts, Isabelle, K Banerjee, Arpan, Hackett, Scott, R Hurst, John, Warnatz, Klau, Gathmann, Benjamin, Weidemann, Jürgen, Berthold, Daniel, and Baumann, Ulrich

Subjects
Antibody deficiency, medicine.medical_specialty, business.industry, Immunology, medicine, MEDLINE, Chest ct, Immunology and Allergy, Radiology, business
Abstract

In the original version of this article unfortunately two authors were missing: Dr. Jurgen Weidemann and Dr. Daniel Berthold. The correct list of authors is presented above.

Published
2019

21. Autosomal-dominant hyper-IgE syndrome is associated with appearance of infections early in life and/or neonatal rash: Evidence from the Italian cohort of 61 patients with elevated IgE

Author

Lorenzini, T, Giacomelli, M, Scomodon, O, Cortesi, M, Rivellini, V, Dotta, L, Soresina, A, Dellepiane, R, Carrabba, M, Cossu, F, Cancrini, C, Specchia, F, Giardino, G, Pignata, C, Plebani, A, Pietrogrande, M, Badolato, R, IPINET (Italian Network for Primary Immunodeficiencies), Lorenzini, T., Giacomelli, M., Scomodon, O., Cortesi, M., Rivellini, V., Dotta, L., Soresina, A., Dellepiane, R. M., Carrabba, M., Cossu, F., Cancrini, C., Specchia, F., Giardino, G., Pignata, C., Plebani, A., Pietrogrande, M. C., and Badolato, R.

Subjects
STAT3, Settore MED/02, Elevated IgE, MUTATIONS, business.industry, Autosomal dominant hyper-IgE syndrome, Immunology, Cohort, Immunology and Allergy, Medicine, medicine.symptom, business, Rash
Published
2019

22. Double-blind, placebo-controlled, randomized trial on low-dose azithromycin prophylaxis in patients with primary antibody deficiencies

Author

Alessandra Vultaggio, Maria Carrabba, Baldassarre Martire, Cinzia Milito, Francesco Cinetto, Federica Pulvirenti, Alessandro Plebani, Antonio Pecoraro, Isabella Quinti, Giovanna Fabio, Andrea Matucci, Vassilios Lougaris, Annarosa Soresina, Giuseppe Spadaro, Giuseppe Lassandro, Damiano Abeni, Stefano Tabolli, Carlo Agostini, Rosa Maria Dellepiane, Milito, Cinzia, Pulvirenti, Federica, Cinetto, Francesco, Lougaris, Vassilio, Soresina, Annarosa, Pecoraro, Antonio, Vultaggio, Alessandra, Carrabba, Maria Cristina, Lassandro, Giuseppe, Plebani, Alessandro, Spadaro, Giuseppe, Matucci, Andrea, Fabio, Giovanna, Dellepiane, Rosa Maria, Martire, Baldassarre, Agostini, Carlo, Abeni, Damiano, Tabolli, Stefano, and Quinti, Isabella

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Haemophilus Infections, Exacerbation, Primary Immunodeficiency Diseases, Immunology, antibiotic prophylaxis, azithromycin, chronic obstructive pulmonary disease, Primary antibody defects, respiratory exacerbation, Placebo, Azithromycin, law.invention, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Internal medicine, antibiotic prophylaxi, Humans, Medicine, Immunology and Allergy, Antibiotic prophylaxis, Adverse effect, COPD, Primary antibody defect, Dose-Response Relationship, Drug, Respiratory tract infections, business.industry, Middle Aged, Pneumonia, Pneumococcal, medicine.disease, Haemophilus influenzae, Streptococcus pneumoniae, 030104 developmental biology, 030228 respiratory system, Female, business, medicine.drug
Abstract

Background Lacking protective antibodies, patients with primary antibody deficiencies (PADs) experience frequent respiratory tract infections, leading to chronic pulmonary damage. Macrolide prophylaxis has proved effective in patients with chronic respiratory diseases. Objective We aimed to test the efficacy and safety of orally administered low-dose azithromycin prophylaxis in patients with PADs. Methods We designed a 3-year, double-blind, placebo-controlled, randomized clinical trial to test whether oral azithromycin (250 mg administered once daily 3 times a week for 2 years) would reduce respiratory exacerbations in patients with PADs and chronic infection–related pulmonary diseases. The primary end point was the number of annual respiratory exacerbations. Secondary end points included time to first exacerbation, additional antibiotic courses, number of hospitalizations, and safety. Results Eighty-nine patients received azithromycin (n = 44) or placebo (n = 45). The number of exacerbations was 3.6 (95% CI, 2.5-4.7) per patient-year in the azithromycin arm and 5.2 (95% CI, 4.1-6.4) per patient-year in the placebo arm (P = .02). In the azithromycin group the hazard risk for having an acute exacerbation was 0.5 (95% CI, 0.3-0.9; P = .03), and the hazard risk for hospitalization was 0.5 (95% CI, 0.2-1.1; P = .04). The rate of additional antibiotic treatment per patient-year was 2.3 (95% CI, 2.1-3.4) in the intervention group and 3.6 (95% CI, 2.9-4.3) in the placebo group (P = .004). Haemophilus influenzae and Streptococcus pneumoniae were the prevalent isolates, and they were not susceptible to macrolides in 25% of patients of both arms. Azithromycin's safety profile was comparable with that of placebo. Conclusion The study reached the main outcome centered on the reduction of exacerbation episodes per patient-year, with a consequent reduction in additional courses of antibiotics and risk of hospitalization.

Published
2019

24. A possible role for B cells in COVID-19? Lesson from patients with agammaglobulinemia

Author

Vassilios Lougaris, Maria Pia Bondioni, Ivano Mezzaroma, Rita Carsetti, Francesco Cinetto, Ombretta Turriziani, Antonio Pecoraro, Cinzia Milito, Alessandro Plebani, Isabella Quinti, Giuseppe Spadaro, Carlo Agostini, Annarosa Soresina, Claudio Maria Mastroianni, Matteo Filippini, Quinti, Isabella, Lougaris, Vassilio, Milito, Cinzia, Cinetto, Francesco, Pecoraro, Antonio, Mezzaroma, Ivano, Maria Mastroianni, Claudio, Turriziani, Ombretta, Pia Bondioni, Maria, Filippini, Matteo, Soresina, Annarosa, Spadaro, Giuseppe, Agostini, Carlo, Carsetti, Rita, and Plebani, Alessandro

Subjects
0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, B iymphocytes, agammaglobulinemia, common variable Immune deficiency, COVID-19, BTK, 03 medical and health sciences, 0302 clinical medicine, Agammaglobulinemia, medicine, Immunology and Allergy, In patient, Viral immunology, business.industry, Common variable immunodeficiency, Clinical course, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, B lymphocytes, Common Variable Immune Deficiency, business, Coronavirus Infections
Abstract

Summary COVID-19 had a mild clinical course in patients with Agammaglobulinemia lacking B lymphocytes, whereas it developed aggressively in Common Variable Immune Deficiency. Our data offer mechanisms for possible therapeutic targets.

Published
2020

25. Circulating follicular helper and follicular regulatory T cells are severely compromised in human CD40 deficiency: A case report

Author

Maria Pia Cicalese, Jolanda Gerosa, Manuela Baronio, Davide Montin, Francesco Licciardi, Annarosa Soresina, Rosa Maria Dellepiane, Maurizio Miano, Lucia Augusta Baselli, Stefano Volpi, Carlo Dufour, Alessandro Plebani, Alessandro Aiuti, Vassilios Lougaris, Georgia Fousteri, Cicalese, Maria Pia, Gerosa, Jolanda, Baronio, Manuela, Montin, Davide, Licciardi, Francesco, Soresina, Annarosa, Dellepiane, Rosa Maria, Miano, Maurizio, Baselli, Lucia Augusta, Volpi, Stefano, Dufour, Carlo, Plebani, Alessandro, Aiuti, Alessandro, Lougaris, Vassilio, and Fousteri, Georgia

Subjects
Male, 0301 basic medicine, Helper-Inducer, T-Lymphocytes, Case Report, AICDA, Hyper-IgM Immunodeficiency Syndrome, Lymphocyte Activation, T-Lymphocytes, Regulatory, 0302 clinical medicine, Activation-induced (cytidine) deaminase, CD40, Immunology and Allergy, Child, CD40LG, class switch recombination, follicular helper T cells, follicular regulatory T cells, hyper-IgM syndrome, somatic hypermutation, Adolescent, Adult, CD40 Antigens, CD40 Ligand, Child, Preschool, Cytidine Deaminase, Female, Humans, Immunophenotyping, Mutation, T-Lymphocytes, Helper-Inducer, Young Adult, biology, Follicular regulatory T cells, Cytidine deaminase, Regulatory, Class switch recombination, Follicular helper T cells, Hyper-IgM syndrome, Somatic hypermutation, Immunology, lcsh:Immunologic diseases. Allergy, Hyper IgM syndrome, 03 medical and health sciences, Immune system, medicine, Preschool, Follicular helper T cell, AICDA, CD40, CD40LG, Class switch recombination, Follicular helper T cells, Follicular regulatory T cells, Hyper-IgM syndrome, Somatic hypermutation, Immunology and Allergy, Immunology, Follicular regulatory T cell, Germinal center, medicine.disease, 030104 developmental biology, Immunoglobulin class switching, biology.protein, lcsh:RC581-607, 030215 immunology
Abstract

Mutations in genes that control class switch recombination and somatic hypermutation during the germinal center (GC) response can cause diverse immune dysfunctions. In particular, mutations in CD40LG, CD40, AICDA, or UNG cause hyper-IgM (HIGM) syndrome, a heterogeneous group of primary immunodeficiencies. Follicular helper (Tfh) and follicular regulatory (Tfr) T cells play a key role in the formation and regulation of GCs, but their role in HIGM pathogenesis is still limited. Here, we found that compared to CD40 ligand (CD40L)- and activation-induced cytidine deaminase (AICDA)-deficient patients, circulating Tfh and Tfr cells were severely compromised in terms of frequency and activation phenotype in a child with CD40 deficiency. These findings offer useful insight for human Tfh biology, with potential implications for understanding the molecular basis of HIGM syndrome caused by mutations in CD40.

Published
2018

26. Ataxia-telangiectasia: Immunodeficiency and survival

Author

Marcel van Deuren, Ásgeir Haraldsson, Corry M.R. Weemaes, Amit Rawat, Anne F.M. Jansen, Nienke J H van Os, Nel Roeleveld, Tomohiro Morio, M.H.D. Schoenaker, Michèl A.A.P. Willemsen, Michiel van der Flier, Nieke T.M. van Driel, Bart P.C. van de Warrenburg, Alex M. Taylor, Charlotte A. Haaxma, Annarosa Soresina, and Amos Etzioni

Subjects
Male, 0301 basic medicine, Oncology, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Ataxia Telangiectasia Mutated Proteins, Hyper-IgM Immunodeficiency Syndrome, Cohort Studies, Hypogammaglobulinemia, 0302 clinical medicine, Agammaglobulinemia, Cause of Death, Neoplasms, Odds Ratio, Immunology and Allergy, Child, Immunodeficiency, IgA Deficiency, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Survival Rate, Phenotype, Female, medicine.symptom, Adult, medicine.medical_specialty, Ataxia, Adolescent, Immunology, Malignancy, Ataxia Telangiectasia, Young Adult, 03 medical and health sciences, Life Expectancy, Internal medicine, medicine, Humans, Survival rate, Proportional Hazards Models, Retrospective Studies, business.industry, Immunologic Deficiency Syndromes, Retrospective cohort study, medicine.disease, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], 030104 developmental biology, Immunoglobulin G, Mutation, Ataxia-telangiectasia, Primary immunodeficiency, business, 030217 neurology & neurosurgery
Abstract

Contains fulltext : 174098.pdf (Publisher’s version ) (Open Access) Ataxia-telangiectasia (AT) is a neurodegenerative disorder characterized by ataxia, telangiectasia, and immunodeficiency. An increased risk of malignancies and respiratory diseases dramatically reduce life expectancy. To better counsel families, develop individual follow-up programs, and select patients for therapeutic trials, more knowledge is needed on factors influencing survival. This retrospective cohort study of 61 AT patients shows that classical AT patients had a shorter survival than variant patients (HR 5.9, 95%CI 2.0-17.7), especially once a malignancy was diagnosed (HR 2.5, 95%CI 1.1-5.5, compared to classical AT patients without malignancy). Patients with the hyper IgM phenotype with hypogammaglobulinemia (AT-HIGM) and patients with an IgG2 deficiency showed decreased survival compared to patients with normal IgG (HR 9.2, 95%CI 3.2-26.5) and patients with normal IgG2 levels (HR 7.8, 95%CI 1.7-36.2), respectively. If high risk treatment trials will become available for AT, those patients with factors indicating the poorest prognosis might be considered for inclusion first.

Published
2017

27. Low Dose Azithromycin Prophylaxis in Primary Antibody Deficiencies

Author

Vassilios Lougaris, Isabella Quinti, Andrea Matucci, Baldassarre Martire, Giuseppe Spadaro, Carlo Agostini, Antonio Pecoraro, Cinzia Milito, Francesco Cinetto, Maria Carrabba, Maria Cristina Pietrogrande, Giovanna Fabio, Alessandro Plebani, Alessandra Vultaggio, Federica Pulvirenti, Stefano Tabolli, Rosamaria Delle Piane, and Anna Rosa Soresina

Subjects
Quality of life, COPD, medicine.medical_specialty, Lung, Bronchiectasis, Exacerbation, business.industry, medicine.drug_class, Immunology, Antibiotics, Azithromycin, medicine.disease, Placebo, Cystic fibrosis, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030228 respiratory system, Internal medicine, medicine, 030212 general & internal medicine, business, medicine.drug
Abstract

Background: Primary Antibody Deficiencies (PAD) patients suffer from frequent respiratory infections leading to chronic pulmonary damage. Macrolides prophylaxis is effective to successfully manage chronic lung diseases as cystic fibrosis, bronchiectasis, COPD. Aim: We conducted a trial to find out if low-dose azithromycin prophylaxis added to the usual care is effective and safe. Methods. A 3-year, phase II, prospective, multicenter, randomized, double-blind, placebo-controlled trial on adult PAD patients with chronic pulmonary disease. Patients received azithromycin 250 mg or placebo once daily three-times a week for 24 months. The primary outcome was the decrease of annual episodes of respiratory exacerbations. Secondary endpoints included: time to the first exacerbation, number of hospitalizations, additional doses of antibiotics, safety. Results: Forty-four patients received azithromycin and 45 placebo. The mean number of exacerbations was 3·6 per patient-year in the azithromycin arm, and 5·2 in the placebo arm (p=0·02). In the azithromycin group the HR for having an acute exacerbation was 0·5 (p=0,03) and the HR for hospitalization was 0.5 (p=0·04). The rate of additional antibiotic treatment per patient-year was 2·3 in the intervention and 3·6 in placebo groups (p=0·004). Improvement in HRQofL was observed in intervention group. Azithromycin’s safety was comparable with placebo. Conclusions: In PAD with respiratory exacerbation, azithromycin prophylaxis reduced exacerbation episodes, additional courses of antibiotics, and risk of hospitalization. It should be considered as a valuable option to add azithromycin to usual treatment.

Published
2019

28. Inborn errors of immunity with atopic phenotypes: A practical guide for allergists

Author

Giuliana Giardino, Bianca Cinicola, Fabio Cardinale, Caterina Cancrini, Stefano Volpi, Annarosa Soresina, Vassilios Lougaris, Francesco La Torre, Gian Luigi Marseglia, Riccardo Castagnoli, Lucia Leonardi, S Corrente, and Silvia Federici

Subjects
lcsh:Immunologic diseases. Allergy, Pulmonary and Respiratory Medicine, Allergy, Atopic phenotypes, Atopy, Inborn errors of immunity, Primary immunodeficiency, Immunology, Immunoglobulin E, medicine.disease_cause, Article, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Immunology and Allergy, 030223 otorhinolaryngology, Immunodeficiency, biology, business.industry, Immune dysregulation, medicine.disease, Settore MED/02, 030228 respiratory system, biology.protein, Allergists, lcsh:RC581-607, business
Abstract

Inborn errors of immunity (IEI) are a heterogeneous group of disorders, mainly resulting from mutations in genes associated with immunoregulation and immune host defense. These disorders are characterized by different combinations of recurrent infections, autoimmunity, inflammatory manifestations, lymphoproliferation, and malignancy. Interestingly, it has been increasingly observed that common allergic symptoms also can represent the expression of an underlying immunodeficiency and/or immune dysregulation. Very high IgE levels, peripheral or organ-specific hypereosinophilia, usually combined with a variety of atopic symptoms, may sometimes be the epiphenomenon of a monogenic disease. Therefore, allergists should be aware that severe and/or therapy-resistant atopic disorders might be the main clinical phenotype of some IEI. This could pave the way to target therapies, leading to better quality of life and improved survival in affected patients.

Published
2021

29. Novel biallelic TRNT1 mutations resulting in sideroblastic anemia, combined B and T cell defects, hypogammaglobulinemia, recurrent infections, hypertrophic cardiomyopathy and developmental delay

Author

Raffaele Badolato, Janet Chou, Vassilios Lougaris, Massimo Bellettato, Michael Seleman, Raif S. Geha, Manuela Baronio, Luisa Gazzurelli, Annarosa Soresina, Alessandro Plebani, Tiziana Lorenzini, and Daniele Moratto

Subjects
0301 basic medicine, Recurrent infections, B cells, business.industry, T cell, Hypogammaglobulinemia, Immunology, Hypertrophic cardiomyopathy, T cells, medicine.disease, TRNT1, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Sideroblastic anemia, 030220 oncology & carcinogenesis, Immunology and Allergy, Medicine, business
Published
2018

30. Clinical heterogeneity of dominant chronic mucocutaneous candidiasis disease: presenting as treatment-resistant candidiasis and chronic lung disease

Author

Raffaele Badolato, Angela Nicoletti, Vassilios Lougaris, Daniela Concolino, Rita Padoan, Donatella Vairo, Silviana Timpano, Fabio Facchetti, Nicola Tamassia, Laura Dotta, Alessandro Plebani, Claudio Pignata, Amelia Licari, Giuliana Giardino, Omar Scomodon, Gian Luigi Marseglia, Annarosa Soresina, Dotta, Laura, Scomodon, Omar, Padoan, Rita, Timpano, Silviana, Plebani, Alessandro, Soresina, Annarosa, Lougaris, Vassilio, Concolino, Daniela, Nicoletti, Angela, Giardino, Giuliana, Licari, Amelia, Marseglia, Gianluigi, Pignata, Claudio, Tamassia, Nicola, Facchetti, Fabio, Vairo, Donatella, and Badolato, Raffaele

Subjects
0301 basic medicine, Azoles, Lung Diseases, Male, Antifungal Agents, Drug Resistance, Autoimmunity, Disease, Drug resistance, medicine.disease_cause, Lung Disease, Chronic mucocutaneous candidiasis, Antifungal Agent, Immunology and Allergy, Medicine, Young adult, Phosphorylation, Child, Leishmaniasis, Immunodeficiency, Candidiasis, Chronic Mucocutaneou, Visceral, Candidiasis, Chronic Mucocutaneous, Candidiasis, Bacterial Infections, Cryptococcosis, Middle Aged, Bronchiectasis, Gain of function STAT1, autoimmunity, bronchiectasis, chronic lung disease, chronic mucocutaneous candidiasis, lymphopenia, STAT1 Transcription Factor, Virus Disease, Chronic lung disease, Virus Diseases, Leishmaniasis, Visceral, Female, Human, Adult, Adolescent, Immunology, Chronic Mucocutaneous, Bacterial Infection, Bronchiectasi, 03 medical and health sciences, Young Adult, Lymphopenia, Cryptococcosi, Humans, Chronic Disease, Cryptococcus neoformans, Mutation, Chronic mucocutaneous candidiasi, business.industry, medicine.disease, 030104 developmental biology, Cryptococcus neoforman, business, Azole
Abstract

In gain-of-function STAT1 mutations, chronic mucocutaneous candidiasis disease (CMCD) represents the phenotypic manifestation of a complex immunodeficiency characterized by clinical and immunological heterogeneity. We aimed to study clinical manifestations, long-term complications, molecular basis, and immune profile of patients with dominant CMCD. We identified nine patients with heterozygous mutations in STAT1, including novel amino acid substitutions (L283M, L351F, L400V). High risk of azole-resistance was observed, particularly when intermittent regimens of antifungal treatment or use of suboptimal dosage occurs. We report a case of Cryptococcosis and various bacterial and viral infections. Risk of developing bronchiectasis in early childhood or gradually evolving to chronic lung disease in adolescent or adult ages emerges. Lymphopenia is variable, likely progressing by adulthood. We conclude that continuous antifungal prophylaxis associated to drug monitoring might prevent resistance to treatment; prompt diagnosis and therapy of lung disease might control long-term progression; careful monitoring of lymphopenia-related infections might improve prognosis.

Published
2016

31. Impaired natural killer cell functions in patients with signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations

Author

Sara Gasperini, Laura Dotta, Ornella Patrizi, Giovanna Tabellini, Marco A. Cassatella, Claudio Pignata, Silvia Parolini, Giuliana Giardino, Annarosa Soresina, Alessandro Plebani, Raffaele Badolato, Donatella Vairo, Nicola Tamassia, Omar Scomodon, Vassilios Lougaris, Rosalba Monica Ferraro, Tabellini, Giovanna, Vairo, Donatella, Scomodon, Omar, Tamassia, Nicola, Ferraro, Rosalba Monica, Patrizi, Ornella, Gasperini, Sara, Soresina, Annarosa, Giardino, Giuliana, Pignata, Claudio, Lougaris, Vassilio, Plebani, Alessandro, Dotta, Laura, Cassatella, Marco A, Parolini, Silvia, and Badolato, Raffaele

Subjects
0301 basic medicine, Adult, Male, Adolescent, medicine.medical_treatment, candidiasi, Immunology, Natural killer cell, Gene Expression, Candidiasis, Cytotoxic activity, IL-15, Natural killer cells, Signal transducer and activator of transcription 1, Signal transducer and activator of transcription 5, Immunology and Allergy, 03 medical and health sciences, medicine, STAT5 Transcription Factor, Humans, STAT1, Chronic mucocutaneous candidiasis, Phosphorylation, Child, STAT5, cytotoxic activity, biology, Candidiasis, Chronic Mucocutaneous, Degranulation, Middle Aged, medicine.disease, candidiasis, Killer Cells, Natural, signal transducer and activator of transcription 5, 030104 developmental biology, medicine.anatomical_structure, Cytokine, STAT1 Transcription Factor, Interleukin 15, signal transducer and activator of transcription 1, Mutation, STAT protein, Cancer research, biology.protein, Cytokines, Female
Abstract

Background Gain-of-function (GOF) mutations affecting the coiled-coil domain or the DNA-binding domain of signal transducer and activator of transcription 1 (STAT1) cause chronic mucocutaneous candidiasis disease. This condition is characterized by fungal and bacterial infections caused by impaired generation of T H 17 cells; meanwhile, some patients with chronic mucocutaneous candidiasis disease might also have viral or intracellular pathogen infections. Objective We sought to investigate the effect of STAT1 GOF mutations on the functioning of natural killer (NK) cells. Methods Because STAT1 is involved in the signaling response to several cytokines, we studied NK cell functional activities and STAT1 signaling in 8 patients with STAT1 GOF mutations. Results Functional analysis of NK cells shows a significant impairment of cytolytic and degranulation activities in patients with STAT1 GOF mutations. Moreover, NK cells from these patients display lower production of IFN-γ in response to IL-15 and reduced proliferation after stimulation with IL-2 or IL-15, suggesting that STAT5 signaling is affected. In addition, signaling studies demonstrate that the increased phosphorylation of STAT1 in response to IFN-α is associated with detectable activation of STAT1 and increased STAT1 binding to the interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) promoter in response to IL-15, whereas STAT5 phosphorylation and DNA binding to IL-2 receptor α (IL2RA) are reduced or not affected in response to the same cytokine. Conclusion These observations suggest that persistent activation of STAT1 might affect NK cell proliferation and functional activities.

Published
2015

32. Chronic Granulomatous Disease in children: a single center experience

Author

Arnalda Lanfranchi, Luisa Imberti, Annarosa Soresina, Michela Zucchi, Alessandra Beghin, Marta Comini, Alessandro Plebani, Fulvio Porta, and Alessandro Montanelli

Subjects
0301 basic medicine, Male, Pediatrics, medicine.medical_specialty, Adolescent, Genetic counseling, Immunology, Inheritance Patterns, Prenatal diagnosis, Kaplan-Meier Estimate, Single Center, Granulomatous Disease, Chronic, 03 medical and health sciences, Chronic granulomatous disease, CGD, Lymphadenitis, medicine, Overall survival, Immunology and Allergy, Humans, CYBB, Retrospective Studies, Primary immunodeficiency, business.industry, Infant, NADPH Oxidases, Bacterial Infections, Pneumonia, medicine.disease, 030104 developmental biology, Child, Preschool, HSCT, Mutation, NADPH Oxidase 2, Female, Molecular diagnosis, Autosomal recessive form, business
Abstract

Chronic Granulomatous Disease (CGD) is caused by the failure of the phagocytes to kill pathogens. We carried out a retrospective analysis of cellular, molecular and clinical features of 14 young patients (mean age at the onset of symptoms and diagnosis: 10 and 25 months, respectively), 7 with autosomal recessive and 7 X-linked form, referred to the Children's Hospital of Brescia between 1999 and 2016. Two new mutations were found, one localized in the CYBB and one in the NCF1 genes. Twelve patients were followed in our institution; the average length of their follow-up after diagnosis was 66 months in X-linked patients and 126 months in autosomal recessive inheritance. The overall survival was 67%, 40% in X-linked and 86% in autosomal recessive form. Eight patients were treated with HSCT. We did not find a clear correlation between the clinical symptoms and the type of mutation, but the fine characterization of the patients was mandatory for therapeutic option, genetic counseling and prenatal diagnosis.

Published
2017

33. Efficacy and Tolerability of a New Pharmaceutical Form of Betamethasone Valerate in the Prevention of Hypertrophic Scars following Anterior Trunk Plastic Surgery: A Preliminary Exploratory Study

Author

M. Bonavita, M. Soresina, D. Boccanera, and F. Bianchi

Subjects
medicine.medical_specialty, integumentary system, business.industry, lcsh:R, Immunology, lcsh:Medicine, Trunk, Betamethasone valerate, Dermatology, Surgery, Plastic surgery, chemistry.chemical_compound, Tolerability, chemistry, Immunology and Allergy, Medicine, Hypertrophic scars, business
Abstract

Hypertrophic scars are fibroproliferative diseases of the skin. Many treatment options are now available, but none is completely effective. The primary objective of this study was to compare the efficacy of a betamethasone valerate (BMV) 2.25 mg plaster versus no treatment in the prevention of hypertrophic scars after anterior trunk plastic surgery. An exploratory, open, prospective, controlled study was carried out on 16 consecutive patients with postoperative wounds. A 12-week daily treatment was initiated after wounds cicatrisation. The effect of a daily application of the plaster was compared to no treatment by dividing the wound into 2–4 parts. The wound evaluation was performed during the treatment period at 2, 4, 8 and 12 weeks, and 6 months after the end of the treatment. A total of 60 wounds was evaluated. Pain and itching improved in both groups after 12 weeks. However, only the wounds treated with BMV plaster showed a significantly greater and more rapid improvement as compared with the non-treated wounds after 4 and 8 weeks of treatment in all the evaluated parameters (p

Published
2014

34. Prospective Study on CVID Patients with Adverse Reactions to Intravenous or Subcutaneous IgG Administration

Author

Federica Borghese, Helene Martini, Massimo Fiorilli, Annarosa Soresina, Vultaggio Alessandra, Isabella Quinti, Andrea Matucci, Carlo Agostini, Andrea Guerra, Alessandro Plebani, Ifigenia Sfika, Giuseppe Spadaro, Marcella Visentini, Quinti, I., Soresina, A., Agostini, C., Spadaro, Giuseppe, Matucci, A., Sfika, I., Martini, H., Borghese, F., Guerra, A., Alessandra, V., Visentini, M., Plebani, A., and Fiorilli, M.

Subjects
Adult, medicine.medical_specialty, Adolescent, Intravenous treatment, Injections, Subcutaneous, Immunology, adverse reaction, Pilot Projects, Subcutaneous immunoglobulin, immunoglobulin therapy, adverse reactions, common variable immunodeficiency, intravenous immunoglobulins, subcutaneous immunoglobulins, Medical microbiology, medicine, Humans, Immunology and Allergy, In patient, Prospective Studies, Infusions, Intravenous, Prospective cohort study, Aged, biology, business.industry, Common variable immunodeficiency, Immunoglobulins, Intravenous, Middle Aged, medicine.disease, Surgery, Common Variable Immunodeficiency, Immunoglobulin G, Anesthesia, Cohort, biology.protein, Antibody, business
Abstract

INTRODUCTION: The multicenter prospective study provides information on adverse reactions to intravenous and subcutaneous immunoglobulin treatment in a cohort of 262 patients with common variable immunodeficiency. Severe adverse reactions are a rare but unpredictable event that might occur also in patients who tolerate substitutive intravenous or subcutaneous immunoglobulin therapy for months or years. RESULTS: Subcutaneous therapy has been proved to be a safe option in the 13 patients who had to stop intravenous treatment and who remained out of immunoglobulin replacement for long periods of time. However, severe reactions to subcutaneous therapy occurred at the first or after several subcutaneous immunoglobulin administrations in 2 out of 13 patients. CONCLUSION: Therefore, patients with previous severe reactions to intravenous immunoglobulin should be considered at particularly high risk for reaction to subcutaneous administration. In these cases, switching from in-hospital administration to home self-administration should be done with extreme care.

Published
2008

35. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study

Author

Quinti I, Soresina A, Guerra A, Rondelli R, Spadaro G, Agostini C, Milito C, Trombetta AC, Visentini M, Martini H, Plebani A, Fiorilli M, IPINet Investigators, De Mattia D, Martire B, Cardinale F, Ranieri G, Silvestri F, Masi M, Cossu F, Anastasio E, Schillirò G, Matucci A, Vultaggio A, Aricò M, Pietrogrande MC, Delle Piane RM, Panisi C, Cambiaghi G, Pignata C, Putti MC, Trizzino A, Bertolini P, Consolini R, Ugazio AG, Duse M, Iacobini M, Moschese V, Cancrini C, Finocchi A, Pesce AM, Cagliuso M, Conti V, Granata G, Mitrevski M, Cecere F, Tovo PA, Martino S, Montin D, Nespoli L, Marinoni M, Pellegrini FP, Cazzola G.A., PESSION, ANDREA, Quinti., I, Soresina, A., Guerra, A., Rondelli, R., Spadaro, Giuseppe, Agostini, C., Milito, C., Trombetta, A. C., Visentini, M., Martini, H., Plebani, A., Fiorilli, M., De Mattia, D., Martire, B., Cardinale, F., Ranieri, G., Silvestri, F., Masi, M., Pession, A., Cossu, F., Anastasio, E., Schillirò, G., Matucci, A., Vultaggio, A., Aricò, M., Pietrogrande, M. C., Delle Piane, R. M., Panisi, C., Cambiaghi, G., Pignata, Claudio, Putti, M. C., Trizzino, A., Bertolini, P., Consolini, R., Ugazio, A. G., Duse, M., Iacobini, M., Moschese, V., Cancrini, C., Finocchi, A., Pesce, A. M., Cagliuso, M., Conti, V., Granata, G., Mitrevski, M., Cecere, F., Tovo, P. A., Martino, S., Montin, D., Nespoli, L., Marinoni, M., Pellegrini, F. P., Cazzola, G. A., Quinti I, Soresina A, Guerra A, Rondelli R, Spadaro G, Agostini C, Milito C, Trombetta AC, Visentini M, Martini H, Plebani A, Fiorilli M, IPINet Investigator, De Mattia D, Martire B, Cardinale F, Ranieri G, Silvestri F, Masi M, Pession A, Cossu F, Anastasio E, Schillirò G, Matucci A, Vultaggio A, Aricò M, Pietrogrande MC, Delle Piane RM, Panisi C, Cambiaghi G, Pignata C, Putti MC, Trizzino A, Bertolini P, Consolini R, Ugazio AG, Duse M, Iacobini M, Moschese V, Cancrini C, Finocchi A, Pesce AM, Cagliuso M, Conti V, Granata G, Mitrevski M, Cecere F, Tovo PA, Martino S, Montin D, Nespoli L, Marinoni M, Pellegrini FP, and Cazzola GA.

Subjects
Male, bronchiectasis, X-linked agammaglobulinemia, Comorbidity, Gastroenterology, Immunoglobulin G, 0302 clinical medicine, Agammaglobulinemia, Risk Factors, Immunology and Allergy, Prospective Studies, Child, Prospective cohort study, 0303 health sciences, biology, Incidence, common variable immunodeficiency, Middle Aged, 3. Good health, Treatment Outcome, Italy, Female, Intravenous, Adult, x-linked agammaglobulinemia, medicine.medical_specialty, immunoglobulin replacement, Adolescent, effectiveness, iga, Immunology, Disease-Free Survival, Injections, Databases, 03 medical and health sciences, Immunoglobulin replacement, common variable immunodeficiency, X-linked agammaglobulinemia, bronchiectasis, IgA, effectiveness, Internal medicine, medicine, Humans, Risk factor, Preschool, Factual, Aged, 030304 developmental biology, Settore MED/38 - Pediatria Generale e Specialistica, Bronchiectasis, business.industry, Common variable immunodeficiency, Infant, Pneumonia, X-Linked, medicine.disease, Databases, Factual, Injections, Intravenous, Child, Preschool, Immunoglobulin A, Follow-Up Studies, Common Variable Immunodeficiency, Genes, X-Linked, Genes, biology.protein, Trough level, business, 030215 immunology
Abstract

A 5-years multicenter prospective study on 201 patients with common variable immunodeficiencies and 101 patients with X-linked agammaglobulinemia over a cumulative follow-up period of 1,365 patient-years was conducted to identify prognostic markers and risk factors for associated clinical co-morbidities, the effects of long-term immunoglobulin treatment and the IgG trough level to be maintained over time required to minimise infection risk. Overall, 21% of the patients with common variable immunodeficiencies and 24% of patients with X-linked agammaglobulinemia remained infection free during the study. A reduction of pneumonia episodes has been observed after initiation of Ig replacement. During the observation time, pneumonia incidence remained low and constant over time. Patients with pneumonia did not have significant lower IgG trough levels than patients without pneumonia, with the exception of patients whose IgG trough levels were persistently < 400 mg/dL. In X-linked agammaglobulinemia, the only co-morbidity risk factor identified for pneumonia by the final multivariable model was the presence of bronchiectasis. In common variable immunodeficiencies, our data allowed us to identify a clinical phenotype characterised by a high pneumonia risk: patients with low IgG and IgA levels at diagnosis; patients who had IgA level < 7 mg/dL and who had bronchiectasis. The effect of therapy with immunoglobulins at replacement dosage for non-infectious co-morbidities (autoimmunity, lymphocytic hyperplasia and enteropathy) remains to be established. A unique general protective trough IgG level in antibody deficiency patients will remain undefined because of the major role played by the progression of lung disease in X-linked agammaglobulinemia and in a subset of patients with common variable immunodeficiencies.

Published
2011

36. Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome

Author

Alberto Vitali, Federica Ortolani, Roberto Rusconi, Srdjan Pasic, Rosa Bacchetta, Fabio Buzi, Donatella Capalbo, Annarosa Soresina, Andrea Taddio, Vassilios Lougaris, Claudio Pignata, Lucia Dora Notarangelo, Mariacarolina Salerno, Małgorzata Pac, Giorgio Radetti, Monique de Vroede, Giuseppe Maggiore, Silvana Martino, Sanal Ozden, Raffaele Badolato, Nella Augusta Greggio, Giovanna Weber, Cinzia Mazza, Alessandro Plebani, Sara Sebnem Kilic, Luigi D. Notarangelo, Mazza, C., Buzi, Paola, Ortolani, F., Karabchuk, Vitali, Notarangelo, L. D., Weber, G., Bacchetta, R., Soresina, A., Lougaris, V., Greggio, N., Taddio, A., Pasic, S., de Vroede, M., Pac, M., Kilic, S. S., Ozden, S., Rusconi, R., Martino, S., Capalbo, D., Salerno, M., Pignata, C., Radetti, G., Maggiore, G., Plebani, A., Notarangelo, Ld., Badolato, R., Çocuk Sağlığı ve Hastalıkları, Buzi, F., Vitali, A., Greggio, N. A., Taddio, Andrea, Uludağ Üniversitesi/Tıp Fakültesi/Pediatri Anabilim Dalı., Kılıç, Sara Şebnem, AAH-1658-2021, Mazza, C, Buzi, F, Ortolani, F, Vitali, A, Notarangelo, Ld, Weber, Giovanna, Bacchetta, R, Soresina, A, Lougaris, V, Greggio, Na, Taddio, A, Pasic, S, de Vroede, M, Pac, M, Kilic, S, Ozden, S, Rusconi, R, Martino, S, Capalbo, D, Salerno, M, Pignata, C, Radetti, G, Maggiore, G, and Plebani, A

Subjects
Time Factors, Autoimmunity, Endocrinopathy, Disease, Type-1, medicine.disease_cause, Mucocutaneous Candidiasis, Homozygosity, Genetic heterogeneity, 0302 clinical medicine, Immunology and Allergy, Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy, Chronic mucocutaneous candidiasis, Child, Polyendocrinopathies, Autoimmune, Priority journal, 0303 health sciences, Heterozygosity, Candidiasis, Genetic analysis, Homozygote, Autoimmune polyendocrinopathy, Middle Aged, Autoimmune regulator, Common, 3. Good health, Child, Preschool, APECED, diagnostic tool, children, Mutations, diagnostic tool, Human, Adult, Heterozygote, animal structures, Adolescent, Clinical article, Immunology, Socio-culturale, 030209 endocrinology & metabolism, APECED, DIAGNOSIS, DIAGNOSIS, Article, 03 medical and health sciences, Young Adult, children, medicine, Humans, Gene mutation, Preschool, Autoantibodies, 030304 developmental biology, Gene amplification, Hepatitis, business.industry, Protein, Dystrophy, Disease type-ı, medicine.disease, Polyendocrinopathies, Autoimmune regulator protein, Preschool child, Regulator aire gene, Type 1 Autoimmune Polyendocrinopathy Syndrome, Regulator, Central Tolerance, Mutation, Genetic association, School child, business, Autoimmune, APECED
Abstract

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive organ-specific autoimmune disorder that is characterized by a variable combination of (i) chronic mucocutaneous candidiasis, (ii) polyendocrinopathy and/or hepatitis and (iii) dystrophy of the dental enamel and nails. We analyzed the AIRE (autoimmune regulator) gene in subjects who presented any symptom that has been associated with APECED, including candidiasis and autoimmune endocrinopathy. We observed that 83.3% of patients presented at least two of the three typical manifestations of APECED, while the remaining 16.7% of patients showed other signs of the disease. Analysis of the genetic diagnosis of these subjects revealed that a considerable delay occurs in the majority of patients between the appearance of symptoms and the diagnosis. Overall, the mean diagnostic delay in our patients was 10.2 years. These results suggest that molecular analysis of AIRE should be performed in patients with relapsing mucocutaneous candidiasis for early identification of APECED. Fondazione Cariplo Fondazione Telethon European Commission (FP7 HLH-cure) (201461) Ministry of Education, Universities and Research (MIUR) Research Projects of National Relevance (PRIN) (2007ACZMMZ_005) Seventh Framework Programme (201461)

Published
2011

37. Reduction of CRKL expression in patients with partial DiGeorge syndrome is associated with impairment of T-cell functions

Author

Daniele Moratto, Sara Gasperini, Marco A. Cassatella, Tiziana Lorenzini, Raffaele Badolato, Rajesh Kumar, Annarosa Soresina, Nicola Tamassia, Alessandro Plebani, Mauro Giacomelli, and Vassilios Lougaris

Subjects
0301 basic medicine, T-Lymphocytes, Lymphocyte Activation, Jurkat cells, Adapter molecule crk, Interferon, DiGeorge syndrome, STAT5 Transcription Factor, Immunology and Allergy, Phosphorylation, Child, STAT5, Regulation of gene expression, c-Fos, biology, Nuclear Proteins, Middle Aged, Immunoglobulin Isotypes, signal transducer and activator of transcription 5, medicine.anatomical_structure, Phenotype, Child, Preschool, CRKL, IL-2, T-cell receptor activation, proliferation, Cytokines, RNA Interference, medicine.drug, Adult, Adolescent, T cell, Immunology, Cell Line, 03 medical and health sciences, Young Adult, medicine, Humans, Gene Silencing, Adaptor Proteins, Signal Transducing, Infant, medicine.disease, Lymphocyte Subsets, 030104 developmental biology, Gene Expression Regulation, Case-Control Studies, biology.protein, Cancer research, Biomarkers
Abstract

Background Partial DiGeorge syndrome (pDGS) is caused by deletion of the 22q11.2 region. Within this region lies CrK-like (CRKL) , a gene encoding an adapter protein belonging to the Crk family that is involved in the signaling cascade of IL-2, stromal cell–derived factor 1α, and type I interferon. Although recurrent infections can be observed in patients with deletion of chromosome 22 syndrome, the immune pathogenesis of this condition is yet not fully understood. Objective We aimed to investigate the role of CRKL in T-cell functional responses in patients affected with pDGS. Methods Protein expression levels and phosphorylation of CRKL were evaluated in patients with pDGS. T-cell functional assays in vitro and gene-silencing experiments were also performed. Results CRKL protein expression, as well as its phosphorylation, were reduced in all patients with pDGS, especially on IL-2 stimulation. Moreover, T cells presented impaired proliferation and reduced IL-2 production on anti-CD3/CD28 stimulation and decreased c-Fos expression. Finally, CRKL silencing in Jurkat T cells resulted in impaired T-cell proliferation and reduced c-Fos expression. Conclusions The impaired T-cell proliferation and reduction of CRKL, phosphorylated CRKL, and c-Fos levels suggest a possible role of CRKL in functional deficiencies of T cells in patients with pDGS.

Published
2016

38. Early Identification of Lung Fungal Infections in Chronic Granulomatous Disease (CGD) Using Multidetector Computer Tomography

Author

Alessandro Plebani, Maria Pia Bondioni, Giuseppe Di Gaetano, Annarosa Soresina, Francesco Laffranchi, Vassilios Lougaris, Tiziana Lorenzini, and Diego Gatta

Subjects
Male, medicine.medical_specialty, Pathology, Immunology, Granulomatous Disease, Chronic, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Medical microbiology, Radiologic sign, Chronic granulomatous disease, Biopsy, Medicine, Humans, Immunology and Allergy, Halo sign, Retrospective Studies, Solitary pulmonary nodule, Lung, medicine.diagnostic_test, Lung Diseases, Fungal, business.industry, Infant, Newborn, Infant, Solitary Pulmonary Nodule, Retrospective cohort study, medicine.disease, Chronic granulomatous disease (CGD), fungal infections, lung CT scan, medicine.anatomical_structure, Early Diagnosis, 030220 oncology & carcinogenesis, Child, Preschool, Female, Radiology, medicine.symptom, business, Tomography, X-Ray Computed, Biomarkers
Abstract

The purpose of this study is to evaluate the possibility of early detection of pulmonary fungal infections by lung CT scan in chronic granulomatous disease (CGD). A retrospective study on 14 patients affected with CGD for a total of 18 infectious episodes was performed. Revision of clinical data and CT scan analysis before and after treatment was performed. The presence of lung nodules

Published
2016

39. Duration of ruptured membranes and vertical transmission of HIV-1: a meta-analysis from 15 prospective cohort studies

Author

Bulterys, M. B., Fowler, M. G., Hanson, I. C., Lemay, M., Mayaux, M. J., Mofenson, L., Newell, M. -L., Peavy, H., Peckham, C., Read, J. S., Rother, C., Simpson, B. J., Van Dyke, R. B., Harris, D. R., Peavy, H. H., Easley, K., Khammy, A., Nugent, R. P., Mitchell, R., Owen, W., Van Dyke, R., Widmayer, S., Bardeguez, A., Hanson, C., Wiznia, A., Luzuriaga, K., Viscarello, R., Ho, D., Koup, R., Chen, I., Krogstad, P., Mullins, J., Wolinsky, S., Korber, B., Walker, B., Ammann, A., Clapp, S., Mcdonald, D., Lapointe, N., Boucher, M., Fauvel, M., Hankins, C., Samson, J., Newell, M. L., Peckham, C. S., Thorne, C. N., Giaquinto, C., Ruga, E., De Rossi, A., Truscia, D., Grosch-Worner, I., Schafer, A., Mok, J., Johnstone, F., Jiminez, J., de Alba, C., Garcia Rodriguez, M. C., Bates, I., de Josee, I., Hawkins, F., Martinez Zapico, R., Pena, J. M., Gonzalez Garcia, J., Arribas Lopez, J. R., Asensi-Botet, F., Otero, M. C., Peerez-Tamarit, D., Moya, A., Galbis, M. J., Scherpbier, H., Boer, K., Bohlin, A. B., Lindgren, S., Anzen, B., Belfrage, E., Lidin-Jansson, G., Levy, J., Barlow, P., Hainaut, M., Peltier, A., Ferrazin, A., De Maria, A., Gotta, C., Mur, A., Vinolas, M., Paya, A., Loepez-Vilchez, M. A., Coll, O., Fortuny, C., Boguna, J., Casellas Caro, M., Canet, Y., Pardi, G., Ravizza, M., Semprini, E., Castagna, C., Fiore, S., Guerra, B., Lanari, M., Bianchi, S., Bovicelli, L., Prati, E., Zanelli, S., Duse, M., Soresina, A., Scaravelli, G., Stegagno, M., De Santis, M., Muggiasca, M. L., Vigano, A., Spinillo, A., Ravagni Probizer, F., Bucceri, A., Rancilio, L., Taylor, G. P., Lyall, H., Penn, Z., Blott, M., Valerius, N. H., Martinelli, P., Buffolano, W., Tibaldi, C., Ziarati, N., Semprini, A., Della Torre, M., Parazzini, F., Dallacasa, P., Bianchi, U., Pachi, A., Mancuso, S., Villa, P., Conti, M., Principi, N., Muggiasca, M., Marchisio, P., Zara, C., Ravagni, F., Vignali, M., Rossi, G., Selvaggi, L., Greco, P., Vimercati, A., Massi, G., Innocenti, T., Fiscella, A., Sansone, M., Benedetto, C., Tadrist, B., Thevenieau, D., Gondry, J., Paulard, B., Alisy, C., Brault, D., Tordjeman, N., Mamou, J., Rozan, M., Colombani, D., Pincemaille, O., Salvetti, A., Chabanier, C., Hernandorena, X., Leroy, J., Schaal, J., Balde, P., Faucher, P., Lachassinne, E., Benoit, S., Douard, D., Hocke, C., Barjot, P., Brouard, J., Delattre, P., Stien, L., Audibert, F., Labrune, P., Vial, M., Mazy, F., Sitbon, D., Crenn-Hebert, C., Floch-Tudal, C., Akakpo, R., Daveau, C., Leblanc, A., Cesbron, P., Duval-Arnould, M., Huraux-Rendu, C., Lemerle, S., Touboul, C., Guerin, M., Maingueneau, C., Reynaud, I., Rousseau, T., Ercoil, V., Lanza, M., Denavit, M., Garnier, J., Lahsinat, K., Pia, P., Allouche, C., Nardou, M., Grall, F., May, A., Dallot, M., Lhuillier, P., Cecile, W., Mezin, R., Bech, A., Lobut, J., Algava, G., Chalvon Dermesay, A., Busuttil, R., Jacquemot, M., Bader-Meunier, B., Fridman, S., Codaccioni, X., Maxingue, F., Thomas, D., Alain, J., De Lumley, L., Tabaste, J., Bailly Salin, P., Seaume, H., Guichard, A., Kebaill, K., Roussouly, C., Botto, C., De Lanete, A., Wipff, P., Cravello, L., De Boisse, P., Leclaire, M., Michel, G., Crumiere, C., Lefevre, V., Le Lorier, B., Pauly, I., Robichez, B., Seguy, D., Delhinger, M., Rideau, F., Talon, P., Benos, P., Huret, C., Nicolas, J., Heller-Roussin, B., Saint-Leger, S., Delaporte, M., Hubert, C., De Sarcus, B., Karoubi, P., Mechinaud, F., Bertcrottiere, D., Bongain, A., Monpoux, F., De Gennes, C., Devianne, F., Nisand, I., Rousset, M., Mouchnino, G., Muray, J., Munzer, M., Quereux, C., Brossard, V., Clavier, B., Allemon, M., Rotten, D., Stephan, J., Varlet, M., Guyot, B., Narcy, P., Bardinet, F., De Caunes, F., Jeny, R., Robin, M., Raison Boulley, A., Savey, L., Berrebi, A., Tricoire, J., Borderon, J., Fignon, A., Guillot, F., Maria, B., Broyard, A., Chitrit, Y., Firtion, G., Mandelbrot, L., Lafay Pillet, M., Parat, S., Boissinot, C., Garec, N., Levine, M., Ottenwalter, A., Schaller, F., Vilmer, E., Courpotin, C., Brunner, C., Ciraru-Vigneron, N., Hatem-Gantzer, G., Fritel, X., Wallet, A., Bouille, J., Milliez, J., Bensaid Mrejen, D., Dermer, E., Noseda, G., Bardou, D., Cressaty, J., Francoual, C., Carlus Moncomble, C., Cohen, H., Blanche, S., Bastion, H., Benifla, J., Benkhatar, F., Berkane, N., Hervee, F., Ronzier, M., Mayaux, Mj., de Martino, M., Tovo, P. -A., Galli, L., Gabiano, C., Ferraris, G., Garetto, S., Palomba, E., Riva, C., Vierucci, A., de Luca, M., Farina, S., Fundaro, C., Genovese, O., Mereu, G., Forni, G. L., Casadei, A., Zuccotti, G. V., Riva, E., Cellini, M., Baraldi, C., Consolini, R., Palla, G., Ruggeri, M., Ciccimarra, F., Guarino, A., Osimani, P., Benaglia, G., Romano, A., De Mattia, D., Caselli, D., Boni, S., Dell'Erba, G., Bassanetti, F., Sticca, M., Timpano, C., Magnani, C., Salvatore, C., Lipreri, R., Tornaghi, R., Pinzani, R., Cecchi, M. T., Bezzi, T., Battisti, L., Bresciani, E., Castelli Gattinara, G., Nasi, C., Pellegatta, A., Mazza, A., Baldi, F., Altobelli, R., Deiana, M., Colnaghi, C., Tarallo, L., Tondo, U., Anastasio, E., Chiriaco, P. G., Ruggeri, C., Scott, G., Hutto, C., O'Sullivan, M., Malmsberry, A., Willoughby, A., Burns, D., Goedert, J., Landesman, S., Minkoff, H., Mendez, H., Holman, S., Rubinstein, A., Durako, S., Muenz, L., Goodwin, S., Bryson, Y., Dillon, M., Nielsen, K., Boyer, P., Liao, D., Keller, M., Deveikis, A., Nesheim, S., Lindsay, M., Lee, F., Nahmias, A., Sawyer, M., Vink, P., Farley, J., Alger, L., Abrams, E., Bamji, M., Lambert, G., Schoenbaum, E., Thomas, P., Weedon, J., Palumbo, P., Denny, T., Oleske, J., Bulterys, M., Simonds, R., Ethier-Ives, J., Rogers, M., Schluchter, M., Kutner, M., Kaplan, S., Kattan, M., Lipshultz, S., Mellins, R., Shearer, W., Sopko, G., Sloand, E., Wu, M., Kind, C., Nadal, D., Rudin, C., Siegrist, C. -A., Wyler, C. -A., Cheseaux, J. -J., Aebi, C., Gnehm, H., Schubiger, G., Klingler, J., Hunziker, U., Kuchler, H., Gianinazzi, M., Buhlmann, U., Biedermann, K., Lauper, U., Irion, O., Brunelli, A., Spoletini, G., Schreyer, A., Hosli, I., Saurenmann, E., Drack, G., Isenschmid, M., Poorbeik, M., Schupbach, J., Perrin, L., Erb, P., Joller, H., Kovacs, A., Stek, A., Chan, L., Khoury, M., Diaz, C., Pacheco-Acosta, E., Tuomala, R., Cooper, E., Mesthene, D., Pitt, J., Higgins, A., Moroso, G., Rich, K., Turpin, D., Cooper, N., Davenny, K., Thompson, B., Andiman, W., Simpson, J., THE INTERNATIONAL PERINATAL HIV, Group, Martinelli, Pasquale, Bulterys M.B., Fowler M.G., Hanson I.C., Lemay M., Mayaux M.J., Mofenson L., Newell M.-L., Peavy H., Peckham C., Read J.S., Rother C., Simpson B.J., Van Dyke R.B., Harris D.R., Peavy H.H., Easley K., Khammy A., Nugent R.P., Mitchell R., Owen W., Van Dyke R., Widmayer S., Bardeguez A., Hanson C., Wiznia A., Luzuriaga K., Viscarello R., Ho D., Koup R., Chen I., Krogstad P., Mullins J., Wolinsky S., Korber B., Walker B., Ammann A., Clapp S., McDonald D., Lapointe N., Boucher M., Fauvel M., Hankins C., Samson J., Newell M.L., Peckham C.S., Thorne C.N., Giaquinto C., Ruga E., De Rossi A., Truscia D., Grosch-Worner I., Schafer A., Mok J., Johnstone F., Jiminez J., de Alba C., Garcia Rodriguez M.C., Bates I., de Josee I., Hawkins F., Martinez Zapico R., Pena J.M., Gonzalez Garcia J., Arribas Lopez J.R., Asensi-Botet F., Otero M.C., Peerez-Tamarit D., Moya A., Galbis M.J., Scherpbier H., Boer K., Bohlin A.B., Lindgren S., Anzen B., Belfrage E., Lidin-Jansson G., Levy J., Barlow P., Hainaut M., Peltier A., Ferrazin A., De Maria A., Gotta C., Mur A., Vinolas M., Paya A., Loepez-Vilchez M.A., Coll O., Fortuny C., Boguna J., Casellas Caro M., Canet Y., Pardi G., Ravizza M., Semprini E., Castagna C., Fiore S., Guerra B., Lanari M., Bianchi S., Bovicelli L., Prati E., Zanelli S., Duse M., Soresina A., Scaravelli G., Stegagno M., De Santis M., Muggiasca M.L., Vigano A., Spinillo A., Ravagni Probizer F., Bucceri A., Rancilio L., Taylor G.P., Lyall H., Penn Z., Blott M., Valerius N.H., Martinelli P., Buffolano W., Tibaldi C., Ziarati N., Semprini A., Della Torre M., Parazzini F., Dallacasa P., Bianchi U., Pachi A., Mancuso S., Villa P., Conti M., Principi N., Muggiasca M., Marchisio P., Zara C., Ravagni F., Vignali M., Rossi G., Selvaggi L., Greco P., Vimercati A., Massi G., Innocenti T., Fiscella A., Sansone M., Benedetto C., Tadrist B., Thevenieau D., Gondry J., Paulard B., Alisy C., Brault D., Tordjeman N., Mamou J., Rozan M., Colombani D., Pincemaille O., Salvetti A., Chabanier C., Hernandorena X., Leroy J., Schaal J., Balde P., Faucher P., Lachassinne E., Benoit S., Douard D., Hocke C., Barjot P., Brouard J., Delattre P., Stien L., Audibert F., Labrune P., Vial M., Mazy F., Sitbon D., Crenn-Hebert C., Floch-Tudal C., Akakpo R., Daveau C., Leblanc A., Cesbron P., Duval-Arnould M., Huraux-Rendu C., Lemerle S., Touboul C., Guerin M., Maingueneau C., Reynaud I., Rousseau T., Ercoil V., Lanza M., Denavit M., Garnier J., Lahsinat K., Pia P., Allouche C., Nardou M., Grall F., May A., Dallot M., Lhuillier P., Cecile W., Mezin R., Bech A., Lobut J., Algava G., Chalvon Dermesay A., Busuttil R., Jacquemot M., Bader-Meunier B., Fridman S., Codaccioni X., Maxingue F., Thomas D., Alain J., De Lumley L., Tabaste J., Bailly Salin P., Seaume H., Guichard A., Kebaill K., Roussouly C., Botto C., De Lanete A., Wipff P., Cravello L., De Boisse P., Leclaire M., Michel G., Crumiere C., Lefevre V., Le Lorier B., Pauly I., Robichez B., Seguy D., Delhinger M., Rideau F., Talon P., Benos P., Huret C., Nicolas J., Heller-Roussin B., Saint-Leger S., Delaporte M., Hubert C., De Sarcus B., Karoubi P., Mechinaud F., Bertcrottiere D., Bongain A., Monpoux F., De Gennes C., Devianne F., Nisand I., Rousset M., Mouchnino G., Muray J., Munzer M., Quereux C., Brossard V., Clavier B., Allemon M., Rotten D., Stephan J., Varlet M., Guyot B., Narcy P., Bardinet F., De Caunes F., Jeny R., Robin M., Raison Boulley A., Savey L., Berrebi A., Tricoire J., Borderon J., Fignon A., Guillot F., Maria B., Broyard A., Chitrit Y., Firtion G., Mandelbrot L., Lafay Pillet M., Parat S., Boissinot C., Garec N., Levine M., Ottenwalter A., Schaller F., Vilmer E., Courpotin C., Brunner C., Ciraru-Vigneron N., Hatem-Gantzer G., Fritel X., Wallet A., Bouille J., Milliez J., Bensaid Mrejen D., Dermer E., Noseda G., Bardou D., Cressaty J., Francoual C., Carlus Moncomble C., Cohen H., Blanche S., Bastion H., Benifla J., Benkhatar F., Berkane N., Hervee F., Ronzier M., Mayaux MJ., de Martino M., Tovo P.-A., Galli L., Gabiano C., Ferraris G., Garetto S., Palomba E., Riva C., Vierucci A., de Luca M., Farina S., Fundaro C., Genovese O., Mereu G., Forni G.L., Casadei A., Zuccotti G.V., Riva E., Cellini M., Baraldi C., Consolini R., Palla G., Ruggeri M., Ciccimarra F., Guarino A., Osimani P., Benaglia G., Romano A., De Mattia D., Caselli D., Boni S., Dell'Erba G., Bassanetti F., Sticca M., Timpano C., Magnani C., Salvatore C., Lipreri R., Tornaghi R., Pinzani R., Cecchi M.T., Bezzi T., Battisti L., Bresciani E., Castelli Gattinara G., Nasi C., Pellegatta A., Mazza A., Baldi F., Altobelli R., Deiana M., Colnaghi C., Tarallo L., Tondo U., Anastasio E., Chiriaco P.G., Ruggeri C., Scott G., Hutto C., O'Sullivan M., Malmsberry A., Willoughby A., Burns D., Goedert J., Landesman S., Minkoff H., Mendez H., Holman S., Rubinstein A., Durako S., Muenz L., Goodwin S., Bryson Y., Dillon M., Nielsen K., Boyer P., Liao D., Keller M., Deveikis A., Nesheim S., Lindsay M., Lee F., Nahmias A., Sawyer M., Vink P., Farley J., Alger L., Abrams E., Bamji M., Lambert G., Schoenbaum E., Thomas P., Weedon J., Palumbo P., Denny T., Oleske J., Bulterys M., Simonds R., Ethier-Ives J., Rogers M., Schluchter M., Kutner M., Kaplan S., Kattan M., Lipshultz S., Mellins R., Shearer W., Sopko G., Sloand E., Wu M., Kind C., Nadal D., Rudin C., Siegrist C.-A., Wyler C.-A., Cheseaux J.-J., Aebi C., Gnehm H., Schubiger G., Klingler J., Hunziker U., Kuchler H., Gianinazzi M., Buhlmann U., Biedermann K., Lauper U., Irion O., Brunelli A., Spoletini G., Schreyer A., Hosli I., Saurenmann E., Drack G., Isenschmid M., Poorbeik M., Schupbach J., Perrin L., Erb P., Joller H., Kovacs A., Stek A., Chan L., Khoury M., Diaz C., Pacheco-Acosta E., Tuomala R., Cooper E., Mesthene D., Pitt J., Higgins A., Moroso G., Rich K., Turpin D., Cooper N., Davenny K., Thompson B., Andiman W., and Simpson J.

Subjects
Time Factors, Epidemiology, Infectious Disease Transmission, Prevention of perinatal transmission, Extraembryonic Membranes, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Cohort Studies, Pregnancy, Risk Factors, INFECTION, Vertical, Immunology and Allergy, HIV Infection, MOTHER-TO-CHILD, Pregnancy Complications, Infectious, Prospective cohort study, prevention of perinatal transmission, vertical transmission, obstetrics/gynaecology, epidemiology, Obstetrics, Transmission (medicine), Infectious, HUMAN-IMMUNODEFICIENCY-VIRUS, MOTHER-TO-CHILD, ZIDOVUDINE PROPHYLAXIS, RISK-FACTORS, TYPE-1, PREGNANCY, INFECTION, TRIAL, PREVENTION, Breast Feeding, Infectious Diseases, Meta-analysis, HUMAN-IMMUNODEFICIENCY-VIRUS, Vertical transmission, Regression Analysis, TRIAL, Female, Delivery, Obstetrics gynaecology, Human, medicine.medical_specialty, Time Factor, Ruptured membranes, Immunology, Regression Analysi, NO, ZIDOVUDINE PROPHYLAXIS, Extraembryonic Membrane, medicine, Humans, TYPE-1, business.industry, Risk Factor, Infant, Newborn, Infant, Obstetric, Delivery, Obstetric, Newborn, PREVENTION, Infectious Disease Transmission, Vertical, Pregnancy Complications, Obstetrics/gynaecology, RISK-FACTORS, Cohort Studie, business
Abstract

Objective: To test the a priori hypothesis that longer duration of ruptured membranes is associated with increased risk of vertical transmission of HIV. Design: The relationship between duration of ruptured membranes and vertical transmission of HIV was evaluated in an individual patient data meta-analysis. Methods: Eligible studies were prospective cohort studies including at least 100 mother-child pairs, from regions where HIV-infected women are counselled not to breastfeed. Analyses were restricted to vaginal deliveries and non-elective Cesarean sections; elective Cesarean section deliveries (those performed before onset of labour and before rupture of membranes) were excluded. Results: The primary analysis included 4721 deliveries with duration of ruptured membranes ≤ 24 h. After adjusting for other factors known to be associated with vertical transmission using logistic regression analysis to assess the strength of the relationship, the risk of vertical HIV transmission increased approximately 2% with an increase of 1 h in the duration of ruptured membranes [adjusted odds ratio, 1.02; 95% confidence interval, 1.01-1.04; for each 1 h increment]. There were no significant interactions of duration of ruptured membranes with study cohort or with any of the covariates, except maternal AIDS. Among women diagnosed with AIDS, the estimated probability of transmission increased from 8% to 31% with duration of ruptured membranes of 2 h and 24 h respectively (P < 0.01). Conclusions: These results support the importance of duration of ruptured membranes as a risk factor for vertical transmission of HIV and suggest that a diagnosis of AIDS in the mother at the time of delivery may potentiate the effect of duration of ruptured membranes. © 2001 Lippincott Williams & Wilkins.

Published
2001

40. The Quality of Life of Children and Adolescents with X-Linked Agammaglobulinemia

Author

Soresina A., Nacinovich R., Bomba M., Cassani M., Molinaro A., Sciotto A., Martino S., Cardinale F., De Mattia D., Putti C., Dellepiane R.M., Felici L., Parrinello G., Neri F., Plebani A., Pierani P., DeMattia D., Martire B., Armenio L., Dammacco F., Ranieri G., Masi M., Miniaci A., Pession A., Rondelli R., Notarangelo L. D., Cao, Cossu F., Del Giacco S., Manconi P., Evangelista I., Magro S., Morgione S., STRISCIUGLIO, PIETRO, Anastasio E., Schillirò G., Paganelli R., Sticca M., Sperlì D., Carpino L., Bernini G., Azzari C., Maggi E., Romagnani S., Matucci A., Vultaggio A., Castagnola E., Gattorno M., Presta G., Civino A., Gambaretto G., Fasoli S., Salpietro C., Pietrogrande M.C., DellePiane R.M., Panisi C., Cambiaghi G., Pietrogrande M., Roncarolo M.G., Aiuti A., Masera G., Biondi A., Sala A., PIGNATA, CLAUDIO, Poggi V., Menna G., Di Nardo R., D'Apuzzo A., Pelliccia A., Correra A., Marone G., SPADARO, GIUSEPPE, Carli M., Zanesco L., Basso G., Putti M.C., Semenzato G., Agostini C., Amato G.M., Aricò M., Trizzino A., Izzi G., Bertolini P., Locatelli F., Zecca M., Rondini G., Marseglia G.L., Maccario R., Bossi G., Favre C., Consolini R., Vecchi V., Sacchini P., Rinaldi G., Ugazio A.G., Rossi P., Livadiotti S., Cancrini C., Finocchi A., Stabile A., Duse M., Iacobini M., Quinti I., Moschese V., Cecere F., Morgese G., Acquaviva A., De Zan G., Strafella S., Tamaro P., Rabusin M., Tovo P.A., Nespoli L., Marinoni M., Porcellini A., Cazzola G.A., Annarosa, Soresina, Renata, Nacinovich, Monica, Bomba, Morena, Cassani, Molinaro, Anna, Antonella, Sciotto, Silvana, Martino, Fabio, Cardinale, Domenico, Mattia, Caterina, Putti, Rosa Maria, Dellepiane, Leonardo, Felici, Giovanni, Parrinello, Francesca, Neri, Alessandro, Plebani, Soresina, A, Nacinovich, R, Bomba, M, Cassani, M, Molinaro, A, Sciotto, A, Martino, S, Cardinale, F, De Mattia, D, Putti, C, Dellepiane, R, Felici, L, Parrinello, G, Neri, F, Plebani, A, Soresina, A., Nacinovich, R., Bomba, M., Cassani, M., Molinaro, A., Sciotto, A., Martino, S., Cardinale, F., De Mattia, D., Putti, C., Dellepiane, R. M., Felici, L., Parrinello, G., Neri, F., Plebani, A., Pierani, P., Demattia, D., Martire, B., Armenio, L., Dammacco, F., Ranieri, G., Masi, M., Miniaci, A., Pession, A., Rondelli, R., Notarangelo, L. D., Cao, Cossu, F., Del Giacco, S., Manconi, P., Evangelista, I., Magro, S., Morgione, S., Strisciuglio, Pietro, Anastasio, E., Schillirò, G., Paganelli, R., Sticca, M., Sperlì, D., Carpino, L., Bernini, G., Azzari, C., Maggi, E., Romagnani, S., Matucci, A., Vultaggio, A., Castagnola, E., Gattorno, M., Presta, G., Civino, A., Gambaretto, G., Fasoli, S., Salpietro, C., Pietrogrande, M. C., Panisi, C., Cambiaghi, G., Pietrogrande, M., Roncarolo, M. G., Aiuti, A., Masera, G., Biondi, A., Sala, A., Pignata, Claudio, Poggi, V., Menna, G., Di Nardo, R., D'Apuzzo, A., Pelliccia, A., Correra, A., Marone, G., Spadaro, Giuseppe, Carli, M., Zanesco, L., Basso, G., Putti, M. C., Semenzato, G., Agostini, C., Amato, G. M., Aricò, M., Trizzino, A., Izzi, G., Bertolini, P., Locatelli, F., Zecca, M., Rondini, G., Marseglia, G. L., Maccario, R., Bossi, G., Favre, C., Consolini, R., Vecchi, V., Sacchini, P., Rinaldi, G., Ugazio, A. G., Rossi, P., Livadiotti, S., Cancrini, C., Finocchi, A., Stabile, A., Duse, M., Iacobini, M., Quinti, I., Moschese, V., Cecere, F., Morgese, G., Acquaviva, A., De Zan, G., Strafella, S., Tamaro, P., Rabusin, M., Tovo, P. A., Nespoli, L., Marinoni, M., Porcellini, A., and Cazzola, G. A.

Subjects
Male, Pediatrics, medicine.medical_specialty, x-linked agammaglobulinemia, Activities of daily living, Adolescent, X-linked agammaglobulinemia, Health Status, Immunology, pedsql 4.0 generic core scale, Quality of life, children, Agammaglobulinemia, Surveys and Questionnaires, Activities of Daily Living, health-related quality of life, parents, medicine, Humans, Immunology and Allergy, PedsQL 4.0 Generic Core Scale, Child, Settore MED/38 - Pediatria Generale e Specialistica, Health related quality of life, quality of live, business.industry, Immunoglobulins, Intravenous, Genetic Diseases, X-Linked, medicine.disease, Socioeconomic Factors, Child, Preschool, Mutation, Quality of Life, Female, X-linked agammaglobulinemia - children - parents - health-related quality of life - PedsQL 4.0 Generic Core Scale, business
Abstract

Introduction: The health-related quality of life in X-linked agammaglobulinemia was investigated in 25 children and adolescents patients through the Italian version of Pediatric Quality of Life Inventory 4.0 Generic Core Scale for patients aged less then 18 years, comparing child perception to that of the parents and the physician's evaluation. The data were compared with the ones of 80 healthy controls and the literature data of a group of patients with rheumatic diseases. Discussion: The agammaglobulinemia subjects perceived a lower global quality of life than the healthy subjects, but significantly higher than the rheumatic diseases controls. The clinical relevance of health-related quality of life assessment in X-linked agammaglobulinemia pediatric patients is discussed. © 2008 Springer Science+Business Media, LLC.

Published
2009

41. Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency

Author

Quinti, I, Soresina, A, Spadaro, G, Martino, S, Donnanno, S, Agostini, C, Claudio, P, Franco, D, Pesce, A, Borghese, F, Guerra, A, Rondelli, R, Plebani, A, De Mattia, D, Martire, B, Cossu, F, Schirillo, G, Castagnola, E, Pietrogrande, M, Delle Piane, R, Putti, C, Trizzino, A, Amato, G, Bertolini, P, Zecca, M, Consolini, R, Moschese, V, Rossi, P, Cancrini, C, Cazzola, G, Quinti, I, Soresina, A, Spadaro, Giuseppe, Martino, S, Donnanno, S, Agostini, C, Claudio, P, Franco, D, MARIA PESCE, A, Borghese, F, Guerra, A, Rondelli, R, Plebani, A, ITALIAN PRIMARY IMMUNODEFICIENCY, Network, SORESINA A., SPADARO G, Pignata, Claudio, and Plebani, A.

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, clinical features, Time Factors, Adolescent, common variable immunodeficiency, Immunology, Immunoglobulins, intravenous immunoglobulins, chronic lung disease, Autoimmune Diseases, Cohort Studies, Age Distribution, Neoplasms, medicine, Immunology and Allergy, Humans, pneumonia, Sinusitis, Prospective cohort study, Child, Preschool, mortality, Aged, Settore MED/38 - Pediatria Generale e Specialistica, Respiratory tract infections, business.industry, Common variable immunodeficiency, Chronic sinusitis, Middle Aged, medicine.disease, Surgery, Survival Rate, Pneumonia, Treatment Outcome, Child, Preschool, Common Variable Immunodeficiency, Female, Follow-Up Studies, Immunotherapy, Cohort, business, Cohort study
Abstract

Common Variable Immunodeficiency belongs to the group of rare diseases encompassing antibody deficiency syndromes of highly variable clinical presentation and outcome. The multicenter prospective study on a cohort of 224 patients with Common Variable Immunodeficiency provides an updated view of the spectrum of illnesses which occurred at the clinical onset and over a long period of follow-up (mean time: 11 years) and information on the effects of long-term immunoglobulin treatment. The mean age at the time of diagnosis was 26.6 years. Seventy-five patients were younger than 14 years of age. The mean age at the onset of symptoms was 16.9 years. This implicates with a mean diagnostic delay of 8.9 years. Respiratory tract infections were the most prominent clinical problem observed at diagnosis and during the follow-up. Intravenous immunoglobulin administration induced a significant reduction in the incidence of acute infections, mainly acute pneumonia and acute otitis. However, a progressive increase in the prevalence of patients with chronic diseases, mainly sinusitis and lung disease, was observed in all age groups, including the pediatric population. The morbidity of Common Variable Immunodeficiency due to all associated clinical conditions increased over time despite an adequate replacement with intravenous immunoglobulins. Our data stressed the need to develop international guidelines for the prevention and therapy of chronic lung disease, chronic sinusitis, chronic diarrhoea, and chronic granulomatosis in patients with humoral immunodeficiencies.

Published
2007

42. Unrelated hematopoietic stem cell transplantation for Cernunnos-XLF deficiency

Author

Maura Faraci, Patrizia Comoli, Laura Banov, Edoardo Lanino, Annarosa Soresina, Daniela Di Martino, Franco Locatelli, Giuseppe Morreale, Alessandro Plebani, and Concetta Micalizzi

Subjects
Male, DNA Repair, T-Lymphocytes, medicine.medical_treatment, Bone Marrow Cells, Hematopoietic stem cell transplantation, medicine.disease_cause, Herpesviridae, Congenital Abnormalities, Immune system, immune system diseases, Lymphopenia, hemic and lymphatic diseases, Immunopathology, medicine, Humans, Transplantation, Homologous, Gammaherpesvirinae, Abnormalities, Multiple, Child, B-Lymphocytes, Transplantation, biology, business.industry, Hematopoietic Stem Cell Transplantation, Immunologic Deficiency Syndromes, biology.organism_classification, Epstein–Barr virus, Treatment Outcome, surgical procedures, operative, Immune System, Pediatrics, Perinatology and Child Health, Immunology, Stem cell, business
Abstract

Cernunnos-XLF deficiency is a rare CI characterized by a defective DNA DSB repair mechanism. Its clinical manifestations are growth retardation, dysmorphic features, malformations, and severe B- and T-cell lymphopenia. BM failure may complicate the clinical picture. To date, there have been no described patients with CSy undergoing allogeneic HSCT. We report a case of CSy treated successfully with unrelated allogeneic HSCT after a reduced-intensity conditioning regimen. Two yr after HSCT, the patient maintains full donor engraftment, normal hematopoiesis, and progressively improving immune competence, thus suggesting that HSCT may be the treatment of choice for CSy.

Published
2009

43. Genetic Causes of Bronchiectasis: Primary Immune Deficiencies and the Lung

Author

Evelina Mazzolari, Annarosa Soresina, Alessandro Plebani, Luigi D. Notarangelo, and Maria Pia Bondioni

Subjects
Pulmonary and Respiratory Medicine, Neutropenia, Bronchiectasis, Lung, Heterogeneous group, business.industry, Respiratory disease, Acquired immune system, medicine.disease, Review article, Common Variable Immunodeficiency, Immune system, medicine.anatomical_structure, Agammaglobulinemia, Immunopathology, Immunology, medicine, Humans, Severe Combined Immunodeficiency, business
Abstract

Primary immune deficiencies (PID) comprise a heterogeneous group of genetically determined disorders that affect development and/or function of innate or adaptive immunity. Consequently, patients with PID suffer from recurrent and/or severe infections that frequently involve the lung. While the nature of the immune defect often dictates the type of pathogens that may cause lung infection, there is substantial overlap of radiological findings, so that appropriate laboratory tests are mandatory to define the nature of the immune defect and to prompt appropriate treatment. At the same time, the recent identification of a large number of PID-causing genes now allows early, even presymptomatic diagnosis, thus representing an essential tool for prevention of lung damage. This review article describes the most common forms of PID, their cellular and molecular bases, and the associated lung abnormalities, and reports on available treatment.

Published
2007

44. Bruton tyrosine kinase mediates TLR9-dependent human dendritic cell activation

Author

Giacomo Tampella, Marco Cattalini, Vassilios Lougaris, Annarosa Soresina, Massimiliano Vitali, Laura Tassone, Raffaele Badolato, Manuela Baronio, Alessandro Plebani, Lougaris, V., Baronio, M., Vitali, M., Tampella, Giacomo, Cattalini, M., Tassone, Laura, Soresina, A., Badolato, Raffaele, and Plebani, A.

Subjects
Lipopolysaccharides, STAT3 Transcription Factor, CpG Oligodeoxynucleotide, Immunology, X-linked agammaglobulinemia, chemical and pharmacologic phenomena, Immunophenotyping, STAT3, TLR9, STAT1, Downregulation and upregulation, immune system diseases, Agammaglobulinemia, BTK, STAT1, STAT3, TLR9, dendritic cells, hemic and lymphatic diseases, medicine, Agammaglobulinaemia Tyrosine Kinase, Immunology and Allergy, Bruton's tyrosine kinase, Humans, Toll-like receptor, biology, hemic and immune systems, Genetic Diseases, X-Linked, Dendritic Cells, Protein-Tyrosine Kinases, medicine.disease, Phenotype, STAT1 Transcription Factor, Oligodeoxyribonucleotides, BTK, Toll-Like Receptor 9, biology.protein, Cancer research, Cytokines, Cell activation, CD80
Abstract

BACKGROUND: Bruton tyrosine kinase (BTK) plays an essential role in various biologic functions of different cell types. Mutations in BTK lead to X-linked agammaglobulinemia (XLA) in humans. BTK was recently linked to the innate immune system, in particular, the Toll-like receptor (TLR) pathway; however, the TLR9 pathway has never been studied in dendritic cells (DCs) of patients with XLA. OBJECTIVE: The aim of this study was to investigate the role of BTK in human DC activation upon TLR9 stimulation. METHODS: DCs of patients with XLA and healthy donors were stimulated via TLR4/9 and evaluated for cell activation and cytokine production. RESULTS: We showed that BTK plays an essential role in DC responses to unmethylated CpG oligodeoxynucleotide: although responses to lipopolysaccaride/TLR4 induce normal DC activation in terms of upregulation of specific markers (CD86, CD83, CD80, HLA-DR), the CpG/TLR9 pathway is completely impaired in patients with XLA. Furthermore, cytokine production upon TLR9 activation in patients with XLA is radically impaired in terms of IL-6, IL-12, TNF-α, and IL-10 production. Interestingly, BTK mediated STAT1/3 upregulation in a TLR9-dependent manner. The important role of BTK in human DC activation was confirmed after incubation of healthy DCs with ibrutinib, the specific BTK inhibitor, which resulted in impairment of TLR9 responses as seen in patients with XLA. CONCLUSION: Analysis of these data suggests that BTK regulates human DC responses upon TLR9 engagement in terms of activation, cytokine production, and STAT1/3 upregulation. These findings may be of important significance for better understanding and managing different clinical conditions, such as agammaglobulinemia and lymphoid malignancies.

Published
2013

45. Correlation of bone marrow abnormalities, peripheral lymphocyte subsets and clinical features in uncomplicated common variable immunodeficiency (CVID) patients

Author

Manuela Baronio, Kim Cattivelli, Daniele Moratto, Vassilios Lougaris, Tiziana Lorenzini, Alessandro Plebani, Annarosa Soresina, Stefania Masneri, and Giacomo Tampella

Subjects
Adult, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Adolescent, T-Lymphocytes, Immunology, B-Lymphocyte Subsets, Bone Marrow Cells, Lymphocyte Activation, Autoimmune Diseases, Flow cytometry, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Recurrence, T-Lymphocyte Subsets, medicine, Humans, Immunology and Allergy, Bone marrow, Young adult, Respiratory Tract Infections, B cell, B cells, CVID, B-Lymphocytes, Bronchiectasis, medicine.diagnostic_test, business.industry, Common variable immunodeficiency, Middle Aged, Flow Cytometry, medicine.disease, Peripheral, Common Variable Immunodeficiency, 030104 developmental biology, medicine.anatomical_structure, Splenomegaly, Female, business, 030215 immunology
Abstract

B cell developmental defects in CVID were recently described in a limited number of cases. To date, a detailed correlation between this maturational defect and the clinical presentation of affected patients has not been reported. In this study, we correlated bone marrow B cell evaluation, peripheral B and T lymphocyte subsets and clinical findings in 15 CVID patients. Early B cell developmental defects were observed in one third of patients. Combined bone marrow and peripheral lymphocytes evaluation allowed to further subdivide CVID patients in three groups with shared clinical features at diagnosis and during follow-up. These data broaden the number of CVID patients with early B cell developmental defects and, together with the peripheral lymphocytes evaluation, offer insight into the related clinical features in affected patients.

Published
2015

46. Mutational Analysis of Human BLyS in Patients with Common Variable Immunodeficiency

Author

Gemma Cattaneo, Roberta Gatta, Antonella Meini, Bodo Grimbacher, Alessandro Plebani, Claretta Gioia Losi, Annarosa Soresina, Ulrich Salzer, and Vassilios Lougaris

Subjects
Adult, Candidate gene, Adolescent, hypogammaglobulinemia, DNA Mutational Analysis, Immunology, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Exon, B-Cell Activating Factor, medicine, Humans, Immunology and Allergy, SNP, B cells, common variable immunodeficiency, Child, B-cell activating factor, Receptor, B cell, Aged, DNA Primers, Genetics, Tumor Necrosis Factor-alpha, Common variable immunodeficiency, Infant, Membrane Proteins, Sequence Analysis, DNA, Middle Aged, medicine.disease, Common Variable Immunodeficiency, medicine.anatomical_structure, Child, Preschool, Mutation
Abstract

BLyS, a TNF family member, is crucial for B cell proliferation and differentiation by acting through its three receptors, TACI, BCMA and BAFF-R. The knock out model for BLyS is characterized by an immunological phenotype reminiscent of the human phenotype of common variable immunodeficiency (CVID). CVID is characterized by a defective B cell compartment, evidencing the putative importance of BLyS in its pathogenesis. On the contrary, the transgenic model for BLys is characterized by autoimmune manifestations, underlying its role in B cell regulation. In fact, mutations in TACI, one of the three BLyS receptors, are associated with CVID. Based on these facts, we hypothesized that BLyS could be a candidate gene for CVID. We screened 78 patients with CVID using DHPLC and direct sequencing: No disease causing mutations were identified. A novel heterozygous single nucleotide polymorphism (SNP) was found in exon 1 of one individual, however this SNP (G189A) does not lead to an amino acid substitution.

Published
2006

47. Mutational Analysis of Human BAFF Receptor TNFRSF13C (BAFF-R) in Patients with Common Variable Immunodeficiency

Author

Luigi D. Notarangelo, Claudia Fiorini, Antonella Meini, Alessandro Plebani, Simona Ferrari, Vassilios Lougaris, Claretta Gioia Losi, Annarosa Soresina, and Antonietta Silini

Subjects
Adult, Heterozygote, Adolescent, hypogammaglobulinemia, DNA Mutational Analysis, Molecular Sequence Data, Immunology, Biology, Receptors, Tumor Necrosis Factor, Gene Frequency, medicine, Humans, Immunology and Allergy, Amino Acid Sequence, RNA, Messenger, B cells, common variable immunodeficiency, Child, B-cell activating factor, BAFF receptor, Gene, Immunodeficiency, B cell, Genetics, Polymorphism, Genetic, Common variable immunodeficiency, Infant, Membrane Proteins, medicine.disease, Phenotype, stomatognathic diseases, medicine.anatomical_structure, Amino Acid Substitution, Child, Preschool, Mutation, Knockout mouse, Leukocytes, Mononuclear, B-Cell Activation Factor Receptor
Abstract

BAFF receptor (BAFF-R/BR3/TNFRSF13C) is a recently identified molecule that specifically binds BLyS, a protein belonging to the tumor necrosis factor (TNF) family, and is involved in survival and maturation of B cells. Recent studies have demonstrated that mice defective in BAFF-R gene exhibit an altered profile of the B cell pool, a phenotype observed in BLyS knockout mice as well. These features suggest that mutations in this gene may result in humoral immunodeficiency. To test this hypothesis, we sequenced the BAFF-R gene in 48 patients with common variable immunodeficiency (CVID) along with 57 healthy controls. We have identified three novel variants present at the heterozygous state leading to amino acid substitutions, and have also confirmed the existence of a previously reported intronic variant. The hereby described novel variants were also present in healthy controls and in the healthy patients' parents. These variants do not affect the expression of BAFF-R neither at the mRNA nor at the protein level, suggesting that these variants represent novel polymorphic variants of the BAFF-R gene.

Published
2005

48. Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome

Author

Anna Virginia Gulino, Patrizia Cavadini, Evelina Mazzolari, Karel Otero, Silvia Pirovano, Laura Tassone, Daniele Moratto, Raffaele Badolato, Luigi D. Notarangelo, Lucia Dora Notarangelo, Roberta Soresina, Silvano Sozzani, David L. Nelson, and Luisa Imberti

Subjects
Adult, Neutropenia, Adolescent, Neutrophils, BONE-MARROW, T-Lymphocytes, Lymphocyte, HEMATOPOIETIC PROGENITOR CELLS, UP-REGULATING CXCR4, FACTOR-I, T-CELLS, CHEMOKINE RECEPTORS, SEVERE NEUTROPENIA, DENDRITIC CELLS, B-LYMPHOCYTES, CUTTING EDGE, DNA Mutational Analysis, Immunology, Gene Expression, Biochemistry, CXCR4, Immunophenotyping, Hypogammaglobulinemia, Chemokine receptor, Agammaglobulinemia, Bone Marrow, medicine, Humans, Stromal cell-derived factor 1, Child, Myelokathexis, B-Lymphocytes, biology, Bacterial Infections, Syndrome, Cell Biology, Hematology, Flow Cytometry, medicine.disease, Chemokine CXCL12, medicine.anatomical_structure, biology.protein, Calcium, Female, Warts, Chemokines, CXC, WHIM syndrome
Abstract

The chemokine receptor CXCR4 and its functional ligand, CXCL12, are essential regulators of development and homeostasis of hematopoietic and lymphoid organs. Heterozygous truncating mutations in the CXCR4 intracellular tail cause a rare genetic disease known as WHIM syndrome (warts, hypogammaglobulinemia, infections, myelokathexis), whose pathophysiology remains unclear. We report CXCR4 function in 3 patients with WHIM syndrome carrying heterozygous truncating mutations of CXCR4. We show that CXCR4 gene mutations in WHIM patients do not affect cell surface expression of the chemokine receptor and its internalization upon stimulation with CXCL12. Moreover, no significant differences in calcium mobilization in response to CXCL12 are found. However, the chemotactic response of both polymorphonuclear cells and T lymphocytes in response to CXCL12 is increased. Furthermore, immunophenotypic analysis of circulating T and B lymphocytes reveals a decreased number of memory B cells and of naive T cells and an accumulation of effector memory T cells associated with a restricted T-cell repertoire. Based on our results, we suggest that the altered leukocyte response to CXCL12 may account for the pathologic retention of mature polymorphonuclear cells in the bone marrow (myelokathexis) and for an altered lymphocyte trafficking, which may cause the immunophenotyping abnormalities observed in WHIM patients. (Blood. 2004;104:444-452)

Published
2004

49. X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease

Author

Claire, Booth, Kimberly C, Gilmour, Paul, Veys, Andrew R, Gennery, Mary A, Slatter, Helen, Chapel, Paul T, Heath, Colin G, Steward, Owen, Smith, Anna, O'Meara, Hilary, Kerrigan, Nizar, Mahlaoui, Marina, Cavazzana-Calvo, Alain, Fischer, Despina, Moshous, Stephane, Blanche, Jana, Pachlopnik Schmid, Jana, Pachlopnick-Schmid, Sylvain, Latour, Genevieve, de Saint-Basile, Michael, Albert, Gundula, Notheis, Nikolaus, Rieber, Brigitte, Strahm, Henrike, Ritterbusch, Arjan, Lankester, Nico G, Hartwig, Isabelle, Meyts, Alessandro, Plebani, Annarosa, Soresina, Andrea, Finocchi, Claudio, Pignata, Emilia, Cirillo, Sonia, Bonanomi, Christina, Peters, Krzysztof, Kalwak, Srdjan, Pasic, Petr, Sedlacek, Janez, Jazbec, Hirokazu, Kanegane, Kim E, Nichols, I Celine, Hanson, Neena, Kapoor, Elie, Haddad, Morton, Cowan, Sharon, Choo, Joanne, Smart, Peter D, Arkwright, Hubert B, Gaspar, Pediatrics, Booth, C., Gilmour, K. C., Veys, P., Gennery, A. R., Slatter, M. A., Chapel, H., Heath, P. T., Steward, C. G., Smith, O., O'Meara, A., Kerrigan, H., Mahlaoui, N., Cavazzana Calvo, M., Fischer, A., Moshous, D., Blanche, S., Pachlopnik Schmid, J., Latour, S., de Saint Basile, G., Albert, M., Notheis, G., Rieber, N., Strahm, B., Ritterbusch, H., Lankester, A., Hartwig, N. G., Meyts, I., Plebani, A., Soresina, A., Finocchi, A., Pignata, Claudio, Cirillo, E., Bonanomi, S., Peters, C., Kalwak, K., Pasic, S., Sedlacek, P., Jazbec, J., Kanegane, H., Nichols, K. E., Hanson, I. C., Kapoor, N., Haddad, E., Cowan, M., Choo, S., Smart, J., Arkwright, P. D., and Gaspar, H. B.

Subjects
Male, Pediatrics, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Clinical Trials and Observations, medicine.medical_treatment, Hematopoietic stem cell transplantation, medicine.disease_cause, Biochemistry, 0302 clinical medicine, Signaling Lymphocytic Activation Molecule Family Member 1, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Medicine, X-Linked Lymphoproliferative Syndrome, Signaling Lymphocytic Activation Molecule Associated Protein, Child, Immunodeficiency, 0303 health sciences, Hematopoietic Stem Cell Transplantation, Intracellular Signaling Peptides and Proteins, Hematology, Middle Aged, 3. Good health, Survival Rate, Child, Preschool, Female, SAP, Adult, medicine.medical_specialty, Adolescent, Immunology, Lymphoproliferative disorders, Receptors, Cell Surface, XLP, SAP, Lymphohistiocytosis, Hemophagocytic, 03 medical and health sciences, Young Adult, Antigens, CD, XLP, Humans, Survival rate, 030304 developmental biology, Settore MED/38 - Pediatria Generale e Specialistica, Hemophagocytic lymphohistiocytosis, business.industry, Infant, Newborn, X-linked lymphoproliferative disease, Infant, Cell Biology, Immune dysregulation, medicine.disease, stem-cell transplantation barr-virus infection hemophagocytic lymphohistiocytosis cutting edge t-cells lymphocytic vasculitis encoding gene sap activation mononucleosis, Lymphoproliferative Disorders, Mutation, business, 030215 immunology
Abstract

X-linked lymphoproliferative disease (XLP1) is a rare immunodeficiency characterized by severe immune dysregulation and caused by mutations in the SH2D1A/SAP gene. Clinical manifestations are varied and include hemophagocytic lymphohistiocytosis (HLH), lymphoma and dysgammaglobulinemia, often triggered by Epstein-Barr virus infection. Historical data published before improved treatment regimens shows very poor outcome. We describe a large cohort of 91 genetically defined XLP1 patients collected from centers worldwide and report characteristics and outcome data for 43 patients receiving hematopoietic stem cell transplant (HSCT) and 48 untransplanted patients. The advent of better treatment strategies for HLH and malignancy has greatly reduced mortality for these patients, but HLH still remains the most severe feature of XLP1. Survival after allogeneic HSCT is 81.4% with good immune reconstitution in the large majority of patients and little evidence of posttransplant lymphoproliferative disease. However, survival falls to 50% in patients with HLH as a feature of disease. Untransplanted patients have an overall survival of 62.5% with the majority on immunoglobulin replacement therapy, but the outcome for those untransplanted after HLH is extremely poor (18.8%). HSCT should be undertaken in all patients with HLH, because outcome without transplant is extremely poor. The outcome of HSCT for other manifestations of XLP1 is very good, and if HSCT is not undertaken immediately, patients must be monitored closely for evidence of disease progression.

Published
2011

50. Molecular characterization of a large cohort of patients with Chronic Granulomatous Disease and identification of novel CYBB mutations: an Italian multicenter study

Author

Domenico De Mattia, Annamaria Ventura, Cecilia Sinibaldi, Lucia Giordani, Gigliola Di Matteo, Paolo Rossi, Claudio Pignata, Antonino Trizzino, Alessandro Plebani, Jan Blancato, Baldassarre Martire, Roberto Rondelli, Rosa Maria Dellepiane, Annarosa Soresina, Andrea Finocchi, Fausto Cossu, Maria Chiriaco, Di Matteo, G., Giordani, L., Finocchi, A., Ventura, A., Chiriaco, M., Blancato, J., Sinibaldi, C., Plebani, A., Soresina, A., Pignata, C., Dellepiane, Rm., Trizzino, A., Cossu, F., Rondelli, R., Rossi, P., De Mattia, D., and Martire, B.

Subjects
Adult, Male, Genotype-phenotype correlation, medicine.medical_specialty, Adolescent, Genotype, Immunology, Biology, medicine.disease_cause, Granulomatous Disease, Chronic, Chronic Granulomatous Disease, CYBB, White People, Cell Line, Cohort Studies, Chronic granulomatous disease, Molecular genetics, Gene duplication, medicine, Missense mutation, Humans, Child, Molecular Biology, Settore MED/38 - Pediatria Generale e Specialistica, Genetics, Mutation, NADPH oxidase, Membrane Glycoproteins, Incidence, Mutation analysi, Infant, Newborn, Infant, NADPH Oxidases, Middle Aged, medicine.disease, Molecular biology, Mutation analysis, Italy, Child, Preschool, NADPH Oxidase 2, biology.protein, Female
Abstract

Chronic Granulomatous Disease (CGD) is a rare inherited disorder in which phagocytes fail to produce antimicrobial superoxide because NADPH oxidase activity is absent. In about 65% of the cases, the disease is due to mutations affecting the X-linked CYBB gene, encoding the gp91(phox) subunit of NADPH oxidase. We investigated 34 CGD male patients by DHPLC and direct sequencing. A mutation was found in the CYBB gene of 33 patients and 9 of these were novel: one non-sense mutation (c.1123 G>T), three missense mutations (c.58G>A; c.1076 G>C; c.1357 T>A), two splice site mutations (c.141+5G>T; c.142-1G>A), one duplication (c.42_45dupCATT), one deletion (c.184delT), and one rare deletion of two non-contiguous nucleotides (c.1287delT+c.1290delC). One patient had the most frequent GT homozygous deletion in exon2 of the NCF-1 gene encoding the p47(phox) subunit of NADPH oxidase. The carrier analysis was performed in 23 patients' mothers and 16 female relatives through molecular and FISH studies. No clear correlation between the severity of clinical symptoms and the type of mutation could be demonstrated. This study further supports the great heterogeneity of the disease and the notion that genetic analysis is a critical step in obtaining a definitive diagnosis for CGD.

Published
2009

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