Background Rheumatoid arthritis (RA) is a chronic inflammatory disease. Sirtuins (SIRTs) are class III histone deacetylase and mammalian SIRT family has seven members, named SIRT1 to SIRT7. SIRTs act epigenetic roles via histone modification, and alter several intracellular signal pathways including NF-κB and MAPK. Accumulating data indicate that SIRTs can affect both innate and adaptive immune responses.
Objectives The aim of the present study was to evaluate the expressions of SIRT2 and SIRT3 in the patients with RA and to determine their potential effects on the disease phenotype.
Methods Fifty-four patients with RA fulfilled ACR-EULAR 2010 classification criteria, and 26 healthy volunteers were enrolled in the study. Disease activity status was determined by the disease activity score (DAS)28-erythrocyte sedimentation rate and patients with >2.6 score were accepted as active. SIRT2, SIRT3 and GAPDH expressions were investigated in peripheral blood mononuclear cells with real-time PCR. Changes in gene expression are represented as fold change relative to one, where control equals one.
Results The SIRT2 expression was higher (1.21±0.05 vs. 1.15±0.07 AU, p<0.001), but the SIRT3 expression was lower (1.05±0.1 vs. 1.18±0.05 AU, p<0.001), in the RA group than in the healthy control group (Figure). However, the SIRT2 (1.19±0.05 vs.1.23±0.04, p=0.01) and SIRT3 (1.01±0.03 vs. 1.10±0.13, p=0.03) expressions were lower in the active RA patients (n=28) than in inactive ones (n=26). On the other hand, their expressions were not significantly correlated with the ESR and the level of CRP (p>0.05 for all). Similarly, their expressions were not significantly different in the patients with and without anti-CCP positivity (p>0.05 for both). Although the SIRT2 expression was similar in the RF positive and negative patients (1.21±0.05 vs. 1.20±0.05 AU p=0.343) the expression of SIRT3 was increased in the former group (1.08±0.13 vs. 1.01±0.03 AU p=0.014).
The SIRT3 expression was higher in the patients receiving corticosteroid (n=39) compared to the not receiving (n=15) (1.06±0.05 vs. 1.01±0.03, p=0.019) although the SIRT2 expression was not significantly different (p>0.05). The uses of methotrexate, sulphasalazine and antimalarial were not altering the SIRT2 and SIRT3 expression (p>0.05 for all). Unfortunately, their expressions were not directly correlated with any laboratory and clinical parameters.
SIRT2 expressions are higher in the active (DAS28>2.6) inactive (DAS28<2.6) and all RA patients than in HCs (A). Conversely, SIRT3 expressions are lower in the former groups (B). However, SIRT2 and SIRT3 expressions are decreased in the active patients compared to the inactive ones (A and B).
Conclusions The SIRT2 expression increases, while the SIRT3 expression decreases in RA. On the other hand, the expressions of SIRT2 and SIRT3 decrease in the active stage of the disease. Therefore, it may be concluded that the fortune of each SIRT is divergent in RA.
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Disclosure of Interest None declared
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