The effect of HLA genotype on disease onset and severity in CTLA-4 insufficiency

INTRODUCTION: Human Cytotoxic-T-lymphocyte-antigen-4 (CTLA-4) insufficiency caused by heterozygous germline mutations in CTLA4 is a complex immune dysregulation and immunodeficiency syndrome presenting with reduced penetrance and variable disease expressivity, suggesting the presence of disease modifiers that trigger the disease onset and severity. Various genetic and non-genetic potential triggers have been analyzed in CTLA-4 insufficiency cohorts, however, none of them have revealed a …