Experience from Zagreb PID Center

Background The Division of Clinical Immunology and Rheumatology, University Hospital Center Zagreb, founded in 1979, became the national Reference Center for Primary Immunodeficiencies (PIDs) in adults in January 2023 and now receives referrals from all regions of Croatia. Over the last decade, the center has expanded clinical, laboratory, and genetic capacities for inborn errors of immunity. Methods We retrospectively analyzed adult PID patients followed at our center between 2014 and 2026, focusing on diagnostic spectrum, treatment, outcomes, and a dedicated common variable immunodeficiency (CVID) cohort. Diagnostic work-up includes extended immunological testing, functional assays, and stepwise genetic analysis (targeted Sanger sequencing, next-generation sequencing [NGS] panels, and whole-exome sequencing), supported by a newly established multidisciplinary team for PIDs. Results A total of 202 adult PID patients were identified, most with antibody deficiencies (129/202; 63.9%), and more than half younger than 40 years at evaluation, with a substantial proportion transitioned from pediatric care. Immunoglobulin replacement therapy was administered to 93/202 patients (46.0%), with increasing use of subcutaneous and facilitated subcutaneous preparations since 2014–2016 in a total of 62 patients. Among 88 CVID patients, 87.5% (77/88) had at least one autoimmune manifestation across hematologic, pulmonary, gastrointestinal, skin, or rheumatologic domains, while malignancies occurred in 18/88 (20.5%) patients; loss of function (LOF) or death was recorded in 8/88 (9.1%). Conclusions The Zagreb PID Center has become the national adult referral center, providing advanced immunologic and genetic diagnostics, multidisciplinary management, and an increasingly broad range of therapies. The substantial burden of autoimmunity and malignancy in CVID, along with notable mortality, highlights the importance of early diagnosis, structured pediatric–adult transition, and sustained long-term monitoring.