IL23R gene variants in relation to IL17A levels and clinical phenotype in patients with ankylosing spondylitis

Abstract

Background IL23 receptor (IL23R) binding by IL23 is required for the maturation of CD4 + cells into Th17 cells and subsequent generation of IL17A and TNF. As IL23R variations contribute to AS susceptibility, we investigated the effect of IL23R variants on cytokine levels and disease measures in an AS cohort. Methods This was a cross-sectional study of AS patients ( n = 334, 90% B27 + , age 45 years). IL23R genotyping for three non-synonymous single-nucleotide polymorphisms (rs11209026, protective allele A; rs10489629, protective allele A; and rs11209032, risk allele A) was done by Taqman RT-PCR. IL23, IL17A, TNF and IL6 concentrations were determined by sandwich ELISA. Genotypic associations were analysed with non-parametric methods. Results Twenty-two AS patients (6.6%) carried the protective rs11209026 A allele, whereas 206 (61.7%) carried the rs11209032A risk allele ( P = 0.03). Two patients homozygous for rs11209026A had late onset, no co-morbidity and undetectable cytokine levels. IL23R genotypes and five common haplotypes were unrelated with age at onset, BASFI or co-morbidity (all P >0.2). There was no overall difference in the concentration of IL17A (184 vs 233 pg/ml, P > 0.2) or IL23 (276 vs 262 pg/ml, P > 0.4) between AS patients and controls, but a global haplotype association ( P = 0.01) was observed for IL23 concentrations. Conclusion Homozygosity for rs11209026A is rare in AS patients, but may ameliorate the clinical presentation. IL17A and IL23 levels are similar in controls and AS patients. IL23R variants influence IL23 levels but not IL17A levels in AS patients, suggesting that IL23R impacts more on cell types other than Th17 cells.

Potential Contribution of IL-27 and IL-23 Gene Polymorphisms to Multiple Sclerosis Susceptibility: An Association Analysis at Genotype and Haplotype Level

“…In our study, we obtained similar results to those obtained by Pidasheva et al, Di Meglio et al and J.C Nossent et al [ 24 , 59 , 60 ], confirming the association of IL-23- R381Q polymorphism with MS under the codominant model after adjustment for age, gender and smoking factors as covariates, as well as after correcting for multiple testing using the FDR method. The presence of the IL-23- R381Q heterozygous genotype can be protective for MS development.…”

“…These results were also reported in a study conducted by Sarin et al in inflammatory diseases (IBD and psoriasis), in which they concluded that IL-23- R381Q variant may confer protection against autoimmunity and excessive inflammation [ 58 ]. Moreover, Pidasheva et al, Di Meglio et al, Nossent et al, confirmed the protective role of the IL-23- R381Q for AS, psoriasis and Crohn disease (CD) [ 24 , 59 , 60 ].…”

Polimorfismos nos genes CCDC122-LACC1 e IL23R e a hanseníase

“…O gene IL23R possui papel significativo em doenças como: doença de Crohn, artrite psoriática, colite ulcerativa, e recentemente, a hanseníase (Hong et al, 2019;Nossent;Sagen-Johnsen;Bakland, 2018;Sakono et al, 2020;Li et al, 2016) (OR: 0,69, P-valor: 3,27×10 -11 ) que apresentou associação a menor risco a doença.…”