Lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency is a rare autosomal recessive genetic disease that presents as a primary immunodeficiency and immune dysregulation caused by biallelic mutations in the LRBA gene [1]. LRBA deficiency leads to decreased CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) expression on T regulatory cells (Tregs) due to defective intracellular trafficking of CTLA-4 protein [1,2]. CTLA-4 has been shown to inhibit the immune response by binding to the CD86 (on the antigen-presenting cell) with higher affinity and removing it from the cell surface. The reduction of the CD86 on the antigen-presenting cell leads to impairment of the farther T cell activation [3]. Furthermore, CTLA-4 signaling has been shown to block CD28 (costimulatory signal) mediated T cell activation and proliferation [4]. CTLA-4 deficient mice die at 3-4 weeks due to uncontrolled T cell proliferation [5].
Hydroxychloroquine Does not Affect CTLA-4 Expression in LRBA Deficiency: Case Report from Siblings with LRBA Deficiency
