Introduction:
CTLA-4 is an immunoglobulin superfamily receptor, primarily expressed by activated T cells and FOXP3+ regulatory T cells.1 CTLA-4 down-regulates the T cell mediated immune response, and thus functions as an immune checkpoint.2 Homozygous CTLA-4 deficiency in mice causes severe fatal immune dysfunction.3,4 In humans, CTLA-4 haploinsufficiency (HI) causes polyclonal T cell hyperactivation, and present with immunodeficiency, antibody mediated autoimmunity and lymphoproliferation in non-lymphoid organs such as gut, lungs, CNS, bone marrow, etc.5-8 Furthermore, CTLA-4 HI predisposes patients to development of various malignancies such as lymphoma and gastric cancers.9,10