Common variable immunodeficiency (CVID) is one of the most widespread primary immune deficiency, affecting approximately 2 to 4 people per 100,000 individuals in the general population. The etiology remains unknown currently, even if several genetic mutations have been described, and no single clinical feature or single laboratory test can establish the diagnosis, which is based on multiple criteria.

CVID is characterized by T and B-cell dysfunction that has a predisposition to an elevated risk of infections, with the typical involvement of the gastrointestinal and respiratory tracts. Apart from this complication, the coexistence of autoimmunity and immunodeficiency appears paradoxical, 66.67% of the CVID patients present concomitant autoimmune disorders. The most common disorders associated with CVID are autoimmune hemolytic anemia, thrombocytopenic purpura, and cytopenias, either concurrently as seen in Evans syndrome or as separate entities. 

The patients suffering from CVID can also manifest gastrointestinal autoimmune disorders (e.g., celiac disease, autoimmune atrophic gastritis, ulcerative colitis etc,) and rheumatologic diseases (e.g., vasculitis, systemic lupus erythematosus, Behçet’s syndrome, arthritis, Sjogren’s disease etc.). The former might pose a peculiar diagnostic challenge, as the celiac‐specific autoantibodies could be absent in patients affected by CVID. Therefore, understanding the clinical impact of autoimmunity and the molecular basis in patients may help manage CVID, and thus preventing its complications and decreasing its diagnostic delay.