Adult-onset combined immunodeficiency associated with primary biliary cholangitis: a case report

Background : Primary immunodeficiency disorders in adulthood often present with heterogeneous infectious and autoimmune manifestations, frequently leading to diagnostic delays. The relationship between immune deficiency and loss of self-tolerance remains incompletely understood. Adult-onset combined immunodeficiency (CID) represents one of the most severe forms within this spectrum, and its association with autoimmune hepatobiliary disease has not been previously reported. Case presentation : A 38-year-old man with recurrent respiratory infections since childhood and bronchiectasis who developed progressive cholestasis, later diagnosed as primary biliary cholangitis based on histopathology and autoimmune markers (AMA-M2 and Sp100). An initial misdiagnosis of systemic lupus erythematosus was later excluded. Immunological evaluation revealed profound lymphopenia, characterized by a marked depletion of naïve CD4⁺ T cells, reduced numbers of B and NK cells, and a T⁻/B⁻/NK⁻ immunophenotype, fulfilling the ESID 2014 criteria for adult-onset CID. Secondary causes were excluded. Despite immunoglobulin replacement, the patient died from severe infections. Conclusion : This case highlights a previously unreported association between adult-onset CID and PBC, underscoring the importance of early immunological evaluation in adults with autoimmunity and severe infections.