Non-infectious pulmonary and gastrointestinal manifestations in primary antibody deficiencies: lessons for the clinic

Primary antibody deficiencies (PADs), especially common variable immunodeficiency (CVID), are clinically significant inborn errors of immunity due to complex phenotypes and long-term complications. This review provides an updated overview of pulmonary and gastrointestinal manifestations in PADs, focusing on CVID. We conducted a structured literature review of original articles, reviews, and guidelines from the last 10 years, using databases such as PubMed and Scopus. The focus was on immunopathogenesis, clinical features, and treatment of noninfectious pulmonary and gastrointestinal complications in CVID. Key shared immunological pathways include B- and T-cell dysregulation, cytokine-driven inflammation, and microbiota alterations. Early recognition of noninfectious complications in CVID is vital to prevent organ damage and improve outcomes. A multidisciplinary, personalized approach involving genetic, immunologic, and microbiologic assessments and specialists including pathologists, pulmonologists, and gastroenterologists is essential, considering the pulmonary-gastrointestinal axis’s role in mucosal immune dysfunction and systemic immune dysregulation.