MicroRNA Signature May Predict Diagnosis and Treatment Response in Patients with PsA – Rheumatology Advisor

Posted: April 1, 2020 at 3:41 am

Compared with control participants, patients with psoriatic arthritis (PsA) display a significantly greater expression of 6 serum microRNAs (miRNAs), according to study results published in Journal of Rheumatology.1 In addition, baseline expression of certain serum miRNAs was associated with treatment response in patients with PsA.

Prior research has suggested that miRNA, small, noncoding RNA molecules, may serve as regulators in the pathogenesis of autoimmune diseases.2 The researchers sought to explore the relationship between serum miRNA levels and PsA.

Patients with PsA (n=31) were enrolled from outpatient rheumatology clinics at St Vincents University Hospital in Dublin, Ireland. All patients underwent baseline clinical and laboratory assessments, including quantification of C-reactive protein (CRP) levels and erythrocyte sedimentation rates (ESR). Follow-up visits were conducted at 3, 6, and 9 months after PsA treatment initiation. Patients were classified as either treatment responders or nonresponders according to the European League Against Rheumatism criteria. A cohort of healthy control participants (n=20) was enrolled from the community. All study participants underwent a peripheral blood draw; a focused immunology panel of 68 miRNAs of interest was analyzed for each serum sample. The miRNA that were differentially expressed between the 2 study groups were selected for further analysis. Area under the receiver operating characteristic curve (ROC) was used to assess the predictive capacity of each miRNA.

Of the identified miRNAs, 6 were significantly overexpressed in patients with PsA compared with control participants; the 6 miRNAs included miR-221-3p, miR-130a-3p, miR-146a-5p, miR-151-5p, miR-26a-5p (all P <.001), and miR-21-5p (P <.01). According to ROC analyses, miR-130a-3p and miR-26a-5p emerged as the strongest predictors of PsA vs healthy control participants, with area under the curve values of 0.866 and 0.894, respectively. When miRNA expression was compared with nonspecific markers of inflammation, including ESR and CRP, only miR-130a-3p (r=0.53; P =.004) and miR-146a-5p (r=0.41; P =.03) correlated with CRP.

In addition, no significant associations were observed between miRNAs and ESR, suggesting that the 6-miRNA signature was PsA-specific and not just a marker of inflammatory disease. In prospective analyses, greater baseline expression of miR-130a-3p (P <.01), miR-221-3p, miR-146a-5p, miR-151a-5p, and miR-26a-5p (all P <.05) was associated with PsA therapeutic response vs nonresponse. Expression profiles did not appear to differ between patients receiving biologic vs nonbiologic therapies. The ROC analysis identified miR-221-3p, miR-130-3p, and miR-146a-3p as the strongest predictors of therapeutic response, with AUC values of 0.747, 0.760, and 0.717 respectively.

The results describe a serum microRNA signature with high discriminative capacity between PsA and control participants, as well as moderate prognostic capacity for PsA treatment response. Further study of these biomarkers is necessary to elucidate the pathogenesis of PsA.

References

1. Wade SM, McGarry T, Wade SC, Fearon U, Veale DJ. Serum microRNA signature as a diagnostic and therapeutic marker in patients in patients with psoriatic arthritis [published online March 1, 2020]. J Rheumatol. doi:10.3899/jrheum.190602

2. Pauley KM, Cha S, Chan EKL. MicroRNA in autoimmunity and autoimmune diseases. J Autoimmun. 2009;32(3-4):189-194.

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