Predictive values of circulating miR-146a and miR-155 for disease activity and clinical response to TNF-α blocking therapy in patients with ankylosing spondylitis

Abstract

Objective: Ankylosing spondylitis is an insidiously progressive and debilitating form of arthritis involving the axial skeleton. MicroRNAs have been reported to act as candidate biomarkers for ankylosing spondylitis diagnosis and progression. The study aimed to assess the roles of circulating miR-146a and miR-155 in ankylosing spondylitis and their prediction to clinical response to TNF-α blocking therapy.

Methods: The study included 62 ankylosing spondylitis patients who were given originator TNFi with a 6-month period. Responders to anti-TNF treatment were defined as those reaching the Assessment of SpondyloArthritis international Society 40 (ASAS40) response at the 6-month interval, and nonresponders were defined those not (n = 24).

Results: The ankylosing spondylitis patients at M0 (before beginning TNFi treatment) had higher serum levels of miR-146a and miR-155 than the healthy controls (p < .0001). Lower serum levels of miR-146a and miR-155 were noted in the responders (n = 38) compared with the nonresponders (n = 24) at different time points after anti-TNF treatment (p < .0001). The serum levels of miR-146a and miR-155 alone or in combination used to predict treatment outcomes produced AUCs of 0.884, 0.902, and 0.936, respectively. We submitted the following variables: miR-146a and miR-155 levels, BASDAI, ASDASCRP, ESR (mm/h), and CRP (mg/L) into multivariate logistic regression analysis, and results showed that higher levels of miR-146a (OR: 13.75, 95%CI: 1.32 to 143.57, p = .029), miR-155 (OR: 5.74, 95% CI: 1.63 to 20.20, p = .006), and ESR (OR: 1.08, 95% CI: 1.01 to 1.15, p = .022) were independent baseline predictors of ASAS40 response at 6-month anti-TNF-a treatment.

Conclusion: These findings obtained from the study suggest that high serum levels of miR-146a and miR-155 could aid in prediction of poor treatment outcomes after TNF-α blocking therapy.

Keywords: ankylosing spondylitis; anti-TNF treatment; hsa-miR-146a; hsa-miR-155; prognosis.