Inborn errors of immunity (IEI) are rare disorders; characterizing their clinical features and underlying genetic causes is essential for both clinical practice and research. Despite advances, causative genes remain unidentified in many patients. Clarifying the genetic basis of IEI is crucial to deepening our understanding of its pathophysiology and improving patient management.
We retrospectively analyzed 100 patients with IEI followed up at National Defense Medical College Hospital between April 2014 and September 2025. Evaluated variables included age, sex, diagnostic category, registration status in the Primary Immunodeficiency Database in Japan version 2 (PIDJ2), use of immunoglobulin replacement therapy (IGRT), and the identification of causative genes.
Patients ranged in age from 0 to 68 years (median: 19.5 years); 65 were male, and 35 were female. Based on the International Union of Immunological Societies (IUIS) classification, the diagnostic categories were predominantly antibody deficiencies (n = 57), combined immunodeficiencies with associated or syndromic features (n = 12), immunodeficiencies affecting cellular and humoral immunity (n = 10), diseases of immune dysregulation (n = 8), congenital defects of phagocyte number or function (n = 4), autoinflammatory diseases (n = 4), defects in intrinsic and innate immunity (n = 2), phenocopies of inborn errors of immunity (n = 2), and complement deficiencies (n = 1). Forty-seven patients were registered in PIDJ2. IGRT was administered to 43 patients (intravenous: 12; subcutaneous: 31). Causative genes were identified in 51 patients. Among the 41 patients who remained without an identified causative gene (excluding those who had completed follow-up), the most common categories were predominantly antibody deficiencies (n = 25, including 15 with common variable immunodeficiency [CVID]) and immunodeficiencies affecting cellular and humoral immunity (n = 6, including 5 with late-onset combined immunodeficiency).
This single-center analysis provides a comprehensive overview of the clinical and genetic characteristics of IEI and highlights that many cases, particularly CVID, still lack an identified genetic cause. Expanding PIDJ2 registration and participating in multicenter collaborative studies may facilitate a more comprehensive understanding of IEI pathophysiology.
