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