Vassilios Lougaris1, Annarosa Soresina2, Manuela Baronio3, Davide Montin4, Silvana Martino4, Sara Signa5, Stefano Volpi5, Marco Zecca6, Maddalena Marinoni7, Lucia Augusta Baselli8, Rosa Maria Dellepiane8, Maria Carrabba9, Giovanna Fabio9, Maria Caterina Putti10, Francesco Cinetto11, Claudio Lunardi12, Luisa Gazzurelli3, Alessio Benvenuto3, Patrizia Bertolini13, Francesca Conti14, Rita Consolini15, Silvia Ricci16, Chiara Azzari16, Lucia Leonardi17, Marzia Duse17, Federica Pulvirenti18, Cinzia Milito18, Isabella Quinti18, Caterina Cancrini19, Andrea Finocchi19, Viviana Moschese20, Emilia Cirillo21, Ludovica Crescenzi22, Giuseppe Spadaro22, Carolina Marasco23, Angelo Vacca23, Fabio Cardinale24, Baldassare Martire25, Antonino Trizzino26, Maria Licciardello27, Fausto Cossu28, Gigliola Di Matteo19, Raffaele Badolato3, Simona Ferrari29, Silvia Giliani30, Andrea Pession14, Alberto Ugazio31, Claudio Pignata21, Alessandro Plebani32. 1. Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili di Brescia, Brescia, Italy. Electronic address: vlougarisbs@yahoo.com. 2. Pediatrics Clinic, ASST- Spedali Civili of Brescia, Brescia, Italy. 3. Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili di Brescia, Brescia, Italy. 4. Division of Pediatric Immunology and Rheumatology, Department of Public Health and Pediatrics, Regina Margherita Children Hospital, University of Turin, Turin, Italy. 5. Centro Malattie Autoinfiammatorie e Immunodeficienze-Clinica Pediatrica e Reumatologia, IRCCS Giannina Gaslini, Genova, and Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili, Università di Genova, Genoa, Italy. 6. Department of Pediatric Hematology of Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 7. Paediatric Department, ASST-Sette Laghi, F. Del Ponte Hospital, Varese, Italy. 8. Department of Pediatrics, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy. 9. Department of Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 10. Department of Women's and Children's Health, Pediatric Hematology-Oncology Unit, University of Padova, Padua, Italy. 11. Padua University, Department of Medicine (DIMED), Internal Medicine I and Rare Disease Center for Immunologic, Rheumatologic and Respiratory Diseases, Ca' Foncello Hospital, Treviso, Italy. 12. Department of Medicine, University of Verona, Verona, Italy. 13. Paediatric Hematology Oncology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. 14. Unit of Pediatrics, University of Bologna, St. Orsola University Hospital, Bologna, Italy. 15. Section of Pediatrics Immunology and Rheumatology, Department of Pediatrics, University of Pisa, Pisa, Italy. 16. Department of Pediatric Immunology, Jeffrey Modell Center for Primary Immunodeficiency, Anna Meyer's Hospital, University of Florence, Florence, Italy. 17. Pediatrics Department, Umberto I Hospital, Sapienza University, Roma, Italy. 18. Department of Molecular Medicine, Sapienza University of Roma, and Unit of Primary Immunodeficiencies in Adults, Department of Infective diseases and Internal Medicine, Policlinico Umberto I, Rome, Italy. 19. University Department of Pediatrics, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital, University of Rome Tor Vergata, and the Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. 20. Department of Pediatrics, Policlinico Tor Vergata, Tor Vergata University, Rome, Italy. 21. Pediatric Section, Department of Translational Medical Science, Federico II University, Naples, Italy. 22. Department of Translational Medical Sciences, Allergy and Clinical Immunology Center for Basic and Clinical Immunology Research, University of Naples Federico II, Naples, Italy. 23. Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy. 24. Department of Pediatrics and Emergency, Pediatric Allergy and Pulmunology Unit, Azienda Ospedaliera-Universitaria Consorziale-Policlinico, Ospedale Pediatrico Giovanni XXIII, Bari, Italy. 25. Pediatric Unit, Monsignor Dimiccoli Hospital, Barletta, Italy. 26. Department of Pediatric Hematology and Oncology, ARNAS Civico Di Cristina and Benfratelli Hospital, Palermo, Italy. 27. Haematology of Oncology Unit, Department of Pediatrics, University of Catania- Catania, Italy. 28. Second Pediatric Clinic, Antonio Cao Hospital, University of Cagliari, Cagliari, Italy. 29. Unit of Medical Genetics, St. Orsola University Hospital, University of Bologna, Bologna, Italy. 30. Department of Molecular and Translational Medicine, A. Nocivelli Institute for Molecular Medicine, University of Brescia, Brescia, Italy. 31. Institute of Child and Adolescent Health, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. 32. Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili di Brescia, Brescia, Italy. Electronic address: alessandro.plebani@unibs.it.
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.
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.
Authors: Di Sun; Jennifer R Heimall; Matthew J Greenhawt; Nancy J Bunin; Marcus S Shaker; Neil Romberg Journal: JAMA Pediatr Date: 2022-02-01 Impact factor: 16.193
Authors: Cristiane J Nunes-Santos; Christopher Koh; Anjali Rai; Keith Sacco; Beatriz E Marciano; David E Kleiner; Jamie Marko; Jenna R E Bergerson; Michael Stack; Maria M Rivera; Gregory Constantine; Warren Strober; Gulbu Uzel; Ivan J Fuss; Luigi D Notarangelo; Steven M Holland; Sergio D Rosenzweig; Theo Heller Journal: J Allergy Clin Immunol Date: 2021-06-01 Impact factor: 10.793
Authors: Roos-Marijn Berbers; Firdaus A A Mohamed Hoesein; Pauline M Ellerbroek; Joris M van Montfrans; Virgil A S H Dalm; P Martin van Hagen; Fernanda L Paganelli; Marco C Viveen; Malbert R C Rogers; Pim A de Jong; Hae-Won Uh; Rob J L Willems; Helen L Leavis Journal: Front Immunol Date: 2020-06-19 Impact factor: 7.561