4.6 Article

Overexpression of TLR7 and TLR9 Occurs Before Onset Symptoms In First-Degree Relatives of Rheumatoid Arthritis Patients

期刊

ARCHIVES OF MEDICAL RESEARCH
卷 53, 期 1, 页码 86-92

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ELSEVIER SCIENCE INC
DOI: 10.1016/j.arcmed.2021.06.010

关键词

Toll-Like Receptors; Rheumatoid Arthritis; Autoimmunity; Innate Immunity

资金

  1. FIS-IMSS, Mexico [FIS/IMSS/PROT/PRIO/13/028]
  2. CONACYT, Mexico

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The study found that the expression levels of TLR7 and TLR9 are elevated in the early stage of rheumatoid arthritis (RA), and may be associated with the production of autoantibodies, suggesting a role of TLR7 in the development of autoantibodies.
Background. Autoantibodies have a central role in the physiopathology of Rheumatoid Arthritis (RA). However, the responsible factors that trigger and perpetuate the autoantibodies production are unknown. Toll-like receptors (TLRs) have been considered as promotors of autoantibodies production to break down the immunotolerance in RA. Aim of the study. Evaluate the expression levels of TLR7 and TLR9 as well as their correlation with autoantibodies in first-degree relatives (FDR) of RA patients (seropositive and seronegative to ACPA), respect to early RA (eRA) and chronic RA (cRA) patients. Methods. We selected 32 RA patients (16 as eRA and 16 as cRA) and 32 FDR of RA patients (16 seropositive and 16 seronegative to ACPA). Expression levels of TLR7 and TLR9 in whole blood samples from each group were measured by real-time PCR using total RNA extracted from each subject. Also, correlation analysis between TLRs expression and autoantibodies was performed. Results. The expression of TLR7 and TLR9 was diminished in RA patients (p < 0.01) but elevated in ACPA- FDR (p < 0.0001) and ACPA+ FDR (p < 0.05) with a positive correlation between them (r = 0.749, p < 0.000). Moreover, the expression levels of TLR7 correlate positively with ACPA levels in both seropositive ACPA+ FDR subjects (r = 0.582, p = 0.018) and eRA patients (r = 0.593, p = 0.020). Conclusions. Our results showed overexpression of TLR7 and TLR9 may occur in preclinical RA subjects. TLR7 overexpression correlated with ACPA levels' production, suggesting TLR7 may play a role in ACPA development. (c) 2021 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.

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