Evaluation of Toll-like-receptor gene family variants as prognostic biomarkers in rheumatoid arthritis

Immunology Letters
Silvia ToricesJose L Fernández-Luna

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main feature is persistent joint inflammation. Toll-like receptors (TLRs) play critical roles in the activation of innate and adaptive immune responses, and influence the activity of NFκB, a key player in chronic inflammation. We aimed at investigating the association of TLR allelic variants with susceptibility and severity of RA through a systematic, high-throughput, analysis of TLR genes. All coding exons and flanking regions of nine members of the TLR family (TLR1-9) were analyzed in 66 patients with RA and 30 healthy controls by next generation sequencing. We focussed on three single allelic variants, N248S in TLR1, Q11L in TLR7 and M1V in TLR8 based on the allelic frequencies in both patient and control populations, the predicted impact on protein function and the novelty in RA research. Analysis of these selected variants in a larger cohort of 402 patients with RA and in 208 controls revealed no association with susceptibility. However, the M1V allele was associated with a lower need for disease-modifying antirheumatic drugs (DMARDs) (p=0.008) and biologic treatments (p=0.021). Functional studies showed that the M1V variant leads to a reduced production of i...Continue Reading

Citations

Apr 3, 2020·Immunotherapy·Lizdany Flórez-ÁlvarezJuan C Hernandez
Dec 7, 2019·Rheumatology·Gabriel Miltenberger-MiltenyiJoão Eurico Fonseca
Jun 2, 2021·Auto- Immunity Highlights·Yolima Puentes-OsorioDaniel Taborda
Aug 6, 2021·ImmunoTargets and Therapy·Sarah UnterbergerSandra Sacre

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