Effects of anti-TNF on MiR expression in monocytes and CD4(+) T-Lymphocytes in spondyloarthritis - CEA - Commissariat à l’énergie atomique et aux énergies alternatives Accéder directement au contenu
Article Dans Une Revue Arthritis and Rheumatology (hoboken, N.j.) Année : 2019

Effects of anti-TNF on MiR expression in monocytes and CD4(+) T-Lymphocytes in spondyloarthritis

Résumé

Background/Purpose: TNFα inhibitors are an effective treatment for many inflammatory diseases. However, their mechanism of action is more complicated than just blocking the targeted cytokine. MicroRNAs are important post-translational regulators of gene expression and their expression has been found deregulated in rheumatic diseases such as rheumatoid arthritis or spondyloarthritis. The general goal of this work is to investigate changes in miR expression in monocytes and CD4+ T-lymphocytes from patients with axial spondyloarthritis during anti-TNF treatment. Methods: Sixty-eight patients with axial spondyloarthritis were enrolled in the study. Among these patients, 63 fulfilled the 2009 ASAS classification criteria (imaging arm) with sacro-iliitis on X-rays (n= 47) or objective signs of inflammation on MRI (n=16) and 72% were HLA-B27 positive. All patients were naïve for biologic treatments at baseline and had an active disease (mean BASDAI score of 49 +/- 19 and mean ASDAS score of 3+/-1) requiring the initiation of a TNFα inhibitor (Etanercept 41, Adalimumab 17, Golimumab 10). Mean CRP at baseline was 12.5 +/-18. At 3 months, the BASDAI response rate was 59%. Blood sample were collected at baseline (M0) and 3 months (M3) after the initiation of the treatment. Monocytes and CD4+ T-lymphocytes were isolated from peripheral blood mononuclear cells and 372 miR were investigated by qPCR. A paired Wilcoxon signed-rank test was used to explore differential expression of miRs between M0 and M3. Results: Pair-wise comparison of miR level before and 3 months after anti-TNF treatment identified 35 differentially expressed (DE) miRs in circulating CD4+ T lymphocytes and 53 DE miRs in monocytes (false discovery rate < 5%). Eighteen miRs were commonly deregulated in both cell types, among which 12 were upregulated and 6 were downregulated after treatment. Strikingly, we found DE miRs before and after treatment in patients with good response to TNF inhibitors while there was little or no DE miRs in non-responders according to BASDAI response criteria. Differentially expressed miRs were not correlated to the CRP levels or to the variation of the CRP between 0 and 3 months. Also, in patients with negative CRP at baseline, we found DE miRs (nominal p-value < 5%) suggesting that the modulation of miRs was not only reflecting a better inflammation control. Conclusion: This work demonstrates that TNF inhibitors might at least partially act by modulating miR expression, especially in patients who respond well to treatment.
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Dates et versions

cea-04457182 , version 1 (14-02-2024)

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  • HAL Id : cea-04457182 , version 1

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Olivier Fogel, Maud Fagny, Elodie Roche, Nelly Sigrist, Jean-François Deleuze, et al.. Effects of anti-TNF on MiR expression in monocytes and CD4(+) T-Lymphocytes in spondyloarthritis. Arthritis and Rheumatology (hoboken, N.j.), 2019, 71. ⟨cea-04457182⟩
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