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FRI0044 Smoking Induces Irreversible Deregulation of Microrna Expression in Rheumatoid Arthritis
  1. K. Andersson,
  2. M. Turkkila,
  3. S. Töyrä,
  4. M. Bokarewa
  1. Dept rheumatology and inflammation research, Inst Medicine, Göteborg, Sweden

Abstract

Background MicroRNA (miR) represent a part of epigenetic contol of autoimmunity and gain increasing attention in the pathogenesis of RA. Genome-wide and candidate miR surveys indicated deregulation of selected miRs in RA blood and synovial tissue. Smoking belongs to enviromental factors with the ability to reprogram epigenetic control. It is also the most studied risk factor in RA being tightly connected to the production of autoantibodies, high levels of oncoprotein survivin, and resistance to antirheumatic therapy (1,2).

Objectives The aim of this study was to determine effect of smoking on the expression of miRs in leukocytes of RA patients.

Methods Leukocytes of the peripheral blood of 46 female RA patients (age 21–69 years, disease duration 1–22 y) were used as a source of miR. Information about smoking status was collected via a questionnaire and identified current smokers (CS, n=12), former smokers (FS, n=21) and never smokers (NS, n=13). We used the Toray 3D-Gene microRNAs assay-based approach to compare the levels of 2598 miRs between the RA patients with different smoking status. For the comparison between the groups we used only miRs with abundant (raw values >100) expression in leukocytes. Smoking and RA-associated miRs were retrived from the available comprehensive reviews (3,4).

Results The number of detectable miR was highest in the PBMC samples of NS. Former and current smoking was associated with a step-wise decreased global miR expression being most severe in CS. We identified 267 miRs, which had an abundant expression in NS. The expression of 93 of these miRs was significantly affected by smoking being 1.75-times lower in FS and CS (p=0.0002). Analyses of miRs, which had previously been reported sensitive to smoking showed that FS+CS had lower expression of the miRs belonging to the let-7 family compared to NS (2.43 times, p=0.034). Additionally, FS had low expression of the miR-17/92 cluster, where miR-17 family was affected most, reduced 2.05 times (p=0.066), followed by miR-19 and 18 families (1.74 times) and miR-92 family (1.56 times). FS had also 2.1 times lower expression of the miR-16 family. The analysis of miRs described in relation to RA showed that 20 of 30 RA-related miRs were abundantly expressed in the studied samples. The expression of miR-16–5p, miR-126–3p, miR-142–3p, miR-150–5p, miR-22–3p and miR-221–3p showed more then 1.75 times difference between FS and NS.

Conclusions Smoking is associated with a global reduction in miR expression in RA patients, where the members of let-7; miR-17/92 and miR-16 families with key roles in regulation of cell cycle progress, tissue development and immune responses clusers are most affected.

  1. Klareskog L et al. A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum. 2006;54(1):38–46

  2. Svensson B et al. Smoking in combination with antibodies to cyclic citrullinated peptides is associated with persistently high levels of survivin in early rheumatoid arthritis: a prospective cohort study. Arthritis Res Ther. 2014;16(1):R12

  3. Churov AV et al. MicroRNAs in rheumatoid arthritis: altered expression and diagnostic potential. Autoimmun Rev. 2015;14(11):1029–37

  4. Vrijens K et al. MicroRNAs as potential signatures of environmental exposure or effect: a systematic review. Environ Health Perspect. 2015;123(5):399–411

Disclosure of Interest None declared

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