Polymorphisms within Genes Coding for IL-17A and F and Their Receptor as Clinical Hallmarks in Ankylosing Spondylitis

Abstract

IL-17A and IL-17F together with their coreceptor (IL-17RA/RC) were reported to play a significant role in the pathogenesis of spondyloarthritis. The group of axial spondyloarthritis comprises ankylosing spondylitis (AS), a rheumatic disease characterized by chronic inflammation of the joints in the spine. This study is aimed at investigating IL-17A, IL-17F, IL-17RA, and IL-17RC polymorphisms as potential biomarkers of disease susceptibility, clinical parameters, and anti-TNF treatment outcome in a cohort of Polish ankylosing spondylitis patients. In total, 328 subjects, including 138 AS patients and 190 healthy volunteers, participated in the study. Genotyping of IL-17A rs2275913 (G/A), IL-17F rs763780 (A/G), IL-17RA rs4819554 (A/G), and IL-17RC rs708567 (G/A) was performed on real-time PCR instrument using LightSNiP assays. No significant differences were revealed in genotype and allele distribution between patients and controls despite the association of the IL-17RC rs708567 AA homozygosity with the earlier onset of the disease. Moreover, some relationships between IL-17F rs763780 and IL-17RA rs4819554 polymorphisms with clinical parameters related to the disease activity and anti-TNF treatment outcome were observed. IL-17F rs763780 G allele was found to be associated with high disease activity and BASDAI after 6 months and poor response to the treatment while higher VAS values were more common among IL-17RA rs4819554 G variant carriers. In conclusion, the IL-17F rs763780 polymorphism should be considered as a promising biomarker of disease activity and anti-TNF treatment outcome. The IL-17RA rs48419554 G allele may serve as a potential marker of disease severity in Polish AS patients.

Expression of long non‑coding RNA NONHSAT227927.1 and its effect on the JAK2/STAT3 signaling pathway and inflammation in patients with ankylosing spondylitis

“…The data obtained by Gong et al ( 35 ) documented that lncRNAs (326C3.7 and 122K13.12) elevated considerably in AS patients with osseous bridges. Inflammatory factors afflict the severity and potential course of AS ( 36 ). A previous study has unveiled that in patients with AS at the active stage, the high level of inflammation (ESR and CRP) is positively correlated with the percentage of regulatory T cells (Tregs) in PMBCs ( 37 ).…”

Searching for New Genetic Biomarkers of Axial Spondyloarthritis

“…Research on the FCGR2A gene is related to other inflammatory diseases, such as chronic periaortitis [ 61 ] or severe pneumonia in A/H1N1 influenza infection [ 62 ]. Other described polymorphisms associated with disease activity are located, for example, within genes coding for IL-33 [ 63 ], IL-17F, and IL-17RA [ 64 ]. A detailed understanding of the pathogenesis of disease, including the functions of genes involved in this process, will allow the development of drugs with new mechanisms of action.…”

Uncovering the Underworld of Axial Spondyloarthritis

“…In this regard, association with axial-SpA was found in variants of the IL-12 p40 subunit, IL-23 p19 subunit, and IL-23R locus. Furthermore, AS susceptibility variants were recognized in IL-23 downstream molecules, including TYK2 and STAT3, as well as in IL-17A , IL-17F and IL-17RA [ 160 , 161 , 162 , 163 ]. Interestingly, HLA-B27 seems to contribute to the upregulation of the IL-23/IL-17 pathway through two distinct mechanisms: (1) UPR and (2) KIR3DL2 binding of HLA-B27 homodimers.…”