IL-17A, IL-17F and IL-23R Gene Polymorphisms in Polish Patients with Rheumatoid Arthritis

Abstract

Among the complex network of inflammatory cells involved in the pathogenesis of rheumatoid arthritis (RA), Th17 cells have recently been identified as key cells in the promotion of autoimmune processes, and joint destruction. The IL-23/Th17 signalling pathway, consisting of IL-23/IL-23R, IL-17A and IL-17F encoding genes, represents a candidate way for RA development with possible involvement in disease susceptibility and effect on disease progression. The present study aimed to determine the association between the polymorphic variants of the IL-17A (rs2275913), IL-17F (rs763780) and IL-23R (rs11209026) genes and RA susceptibility, progression and response to therapy with TNF-α inhibitors. Eighty-nine patients and 125 healthy individuals were investigated. The IL-17A polymorphism was found to affect RA progression and response to anti-TNF treatment. Female patients carrying the IL-17A wild-type genotype more frequently presented with stage 4 (8/24 vs. 6/47; p = 0.058) and were characterized by more active disease (the highest DAS28 score >5.1) after 3 months of therapy with the TNF inhibitors (12/23 vs. 15/45; p = 0.040). The IL-17F polymorphism appeared to be associated with susceptibility to the disease. The presence of the IL-17F minor variant (OR 3.97; p < 0.001) and its homozygosity (OR 29.62; p < 0.001) was more frequent among patients than healthy individuals. These results suggest that the polymorphisms within the IL-17A and IL-17F genes play a significant role in RA.

Th17 cell pathogenicity and plasticity in rheumatoid arthritis

“…IL‐23, a proinflammatory cytokine, has participated in the pathogenicity of Th17 cells in autoimmune diseases . It was detected in the serum of RA patients with the overproduction of IL‐17, TNF, or IFN‐γ . Anti‐IL‐23 was shown to relieve the symptoms of RA, illustrating its therapeutic promise in patients .…”

Interleukin 6 gene polymorphism is associated with protein serum level and disease activity in Polish patients with rheumatoid arthritis

“…Cause of this therapy resistance is still unknown, although its inefficiency could be partially attributed to genetic differences between patients. Our previous studies have shown that polymorphisms within genes coding for TNF‐α and its receptor, as well as IL‐17A, may be considered factors affecting therapy outcome. In this present study, we concentrated on another pro‐inflammatory cytokine involved in RA aetiology, interleukin 6 (IL‐6).…”

The role of IL‐23 receptor signaling in inflammation‐mediated erosive autoimmune arthritis and bone remodeling

“…In PsA, treatment with anti‐IL‐23 antibodies have shown beneficial effects but not in RA so far. Another finding supporting this hypothesis, is the notion that polymorphisms in the IL‐23 receptor (IL‐23R) have been linked to susceptibility for psoriasis and PsA , but are still a matter of debate in RA (Table ) .…”