Association of IL-10 receptor 2 (IL10RB) SNP with systemic sclerosis

Abstract

Interleukin-10 (IL-10) signaling has been suggested to play a role in systemic sclerosis (SSc). IL10RB codes for IL-10 receptor 2 (IL-10R2), a component shared in receptor complexes for IL-10, IL-22, IL-26 and interferon (IFN)-lambda. In this study, we examined association of IL10RB polymorphism with susceptibility to SSc. Genotype A/A at rs2834167 (47K/K) was significantly increased in diffuse cutaneous SSc (dcSSc) (41.3% in dcSSc, 20.9% in controls, P=0.0018, odds ratio=2.67). A SNP in the 5' flanking region of IL10RB, rs999788, also showed association with dcSSc; however, this association was shown to be secondarily caused by linkage disequilibrium with rs2834167. Significant association was not observed in limited cutaneous SSc (lcSSc). Presence of anti-topoisomerase I antibody was also associated with rs2834167A/A genotype (P=0.0019). Serum IL-10 level was significantly associated with the number of rs2834167A allele (P=0.007). These findings suggested that signaling through IL-10R2 may play a causative role in dcSSc.

Association analysis of class II cytokine and receptor genes in vitiligo patients

“…Earlier investigations have yielded genetic associations with various immune-related diseases from this region: multiple sclerosis [35], systemic sclerosis [36], graft-versus-host disease [37], systemic lupus erythematosus [38], and asthma [39]. Several allelic associations were found.…”

“…Rs2834167A/G is a non-synonymous SNP that causes lysine/glutamate substitution at postition 47 in IL-10R2 peptide. The A allele was more common in familial vitiligo group, which was also apparent in patients of systemic sclerosis [36] and systemic lupus erythematosus [38] studies. Further, the respective IL10RB mRNA had unchanged expression in vitiligo skin, but was upregulated in patients PBMCs [15].…”

Cytokines in the immunopathology of systemic sclerosis

“…Blockade of janus kinase 2 (JAK2) in the fibrosis-induced mouse model suppresses fibrosis indicating the importance of the transcription factor STAT-3 [81]. IL-10 too was found to be increased in the sera of SSc patients and correlated with skin extent and pulmonary fibrosis [82], but some studies suggest an opposing role of IL-10 in the fibrotic process [83]. On the other hand, the prototypic Th1 cytokine IFN-γ has anti-fibrotic property by inhibiting the expression of pro-collagen genes, thereby counter-acting the stimulatory effects of TGF-β [84].…”

IL-22 capacitates dermal fibroblast responses to TNF in scleroderma

“…A genetic association of IL-10RB to diffuse SSc and the presence of autoantibodies have been recently reported 11. The IL-22 receptor is expressed in non-hematopoietic cells of the outer body barriers, in particular, epithelial cells of the digestive/respiratory tract and keratinocytes in the skin 12 13.…”