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.