AbstractBackgroundSeveral studies have suggested that polymorphisms within genes encoding T‐lymphocyte immune regulating molecules: CD28, CTLA‐4, and ICOS, may alter the signaling process and subsequently could be involved in susceptibility to a broad spectrum of autoimmune diseases.MethodsThis study aimed to replicate associations between common polymorphisms in the 2q33.2 cluster and susceptibility to pemphigus foliaceus (PF) in the Tunisian population. We investigated seven polymorphisms: rs3116496 and rs1879877 (CD28), rs231775, rs3087243, and (AT)n repeat (CTLA4); rs11889031 and rs10932029 (ICOS) in a case–control study which enrolled 106 Tunisian PF patients and 205 matched healthy controls.ResultsWe confirmed the associations with CTLA4((AT)13, p = 0.00137, OR = 3.96 and (AT)20, p = 0.008, OR = 5.22; respectively) and ICOS genes (rs10932029>CT, p = 0.034, OR = 2.12 and rs10932029>TT, p = 0.04 and OR = 0.41).ConclusionOur results indicate that susceptibility to PF is located in the proximal and the distal 3′ flanking region of the CTLA4/ICOS promoter. These findings may open avenues to the treatment of patients with biological drugs targeting CTLA4/ICOS molecules, in a personalized manner to achieve more effective treatment.