Cytokine gene polymorphisms in Tunisian endemic pemphigus foliaceus: a possible role of il-4 variants.

Polymorphism in the genes of TH2 cytokines and/or theirs receptors can influence serum cytokine levels in and the switch to the pathologic IgG4 auto-antibodies. In order to underline the role of these genes in the aethiopathogenesis of Pemphigus Foliaceus, we conduct a familial and a case control studies including 80 Tunisian patients, 147 related subjects and 160 matched healthy controls. We investigated, by PCR-RFLP technique, seven nucleotide polymorphisms: rs2243250 in promoter region of IL4 gene, rs47877948, rs3024530 and rs30246223 in the IL4R gene, rs1881457and rs205412 SNPs in IL13 gene and rs535036 in IL13RA2 gene. After Bonferroni adjustment, T allele and the TT genotype of IL4-590 were significantly increased in the PF patients group compared to healthy controls. This association was confirmed by the family study. Interestingly, the serum IL-4 levels were significantly increased in patients with the TT genotype compared to CT or CC genotypes. Interestingly, the IL4/IL13:T-A-C haplotype exhibited a significant effect on PF susceptibility. In addition, a significant gene-gene interaction between the IL4/IL4R (TACA) significantly increases in PF patients as compared to controls. These findings assess the role of the IL4/IL4R axis in the aethiopathogenesis of Tunisian endemic PF by the induction of a high transcriptional activity which could enhance the T-cell balance and inducing immunoglobulin isotype switching.