Immune deficiency and autoimmunity in patients with CTLA-4 (CD152) mutations

Immune deficiency disorders are a heterogeneous group of diseases of variable genetic aetiology. While the hallmark of immunodeficiency is susceptibility to infection, it is increasingly clear that autoimmunity is prevalent, suggestive of a more general immune dysregulation in some cases. With the increasing use of genetic technologies, the underlying causes of immune dysregulation are beginning to emerge. Here we provide a review of the heterozygous mutations found in the immune checkpoint protein CTLA-4, identified in cases of common variable immunodeficiency disorders (CVID) with accompanying autoimmunity. Study of these mutations provides insights into the biology of CTLA-4 as well as suggesting approaches for rational treatment of these patients.