Autoimmunity in common variable immunodeficiency.

Objective: Common variable immunodeficiency (CVID) is a primary immunodeficiency that is clinically heterogeneous, characterized by both infectious and noninfectious complications. Although the hallmark of disease presentation is commonly a history of recurrent sinopulmonary infections, autoimmunity and noninfectious inflammatory conditions are increasingly associated with CVID. Data sources: A comprehensive literature search using PubMed of basic science and clinical articles was performed. Study selections: Articles discussing the association of autoimmunity with primary immunodeficiency, specifically CVID, were selected.

Results: The most common autoimmune conditions are cytopenias, including immune thrombocytopenia purpura and hemolytic anemia, but organ-specific autoimmune/inflammatory complications involving the gastrointestinal, skin, joints, connective tissue, and respiratory tract. In most cases, immunoglobulin replacement therapy does not ameliorate or treat these inflammatory complications, and additional immunomodulatory treatments are needed.

Conclusion: Mechanisms producing these conditions are poorly understood but include cytokine and cellular inflammatory pathways, and loss of tolerance to self-antigens through the multiple signaling molecules and pathways common to tolerance and immune deficiency.