Table 4.

CVID-relevant genes and associated disorders

Gene defect	Protein function	Clinical Manifestation	Treatment
LRBA Loss of function	Assists in the vesicle trafficking and the turnover of the checkpoint of CTLA4	splenomegaly and hepatomegaly, autoimmunity, manifesting as immune-mediated cytopenias and organ-specific autoimmunity, and chronic diarrhea	Abatacept
CTLA4 Loss of function	An important regulator of T cell activation and mediator of regulatory T cell function	hypogammaglobulinemia, diarrhea/enteropathy, ILD, respiratory infections, lymphocytic organ infiltration, and splenomegaly	Abatacept
STAT3 Gain of function	Transcription factor tightly controlled by numerous cytokines, growth factors, and hormones	autoimmunity, including autoimmune hemolytic anemia, autoimmune thrombocytopenia, enteropathy, and type 1 diabetes mellitus as well as lymphadenopathy and hepatosplenomegaly	Jakinibs and Tocilizumab
PIK3CD Gain of function	Enzyme involved in growth and proliferation of white blood cells with potent affects upon B and T cell activation	recurrent respiratory infections and benign lymphoproliferation with bronchiectasis, GI disease, autoimmune cytopenias, glomerulonephritis, arthritis, and colitis	Rapamycin

^*Adapted from the Current Understanding and Recent Developments in Common Variable Immunodeficiency Associated Autoimmunity¹⁰