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

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
Publication statusAccepted/In press - Jan 1 2020


  • Bruton tyrosine kinase
  • chronic lung disease
  • X-linked agammaglobulinemia

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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