Plasma levels of miR-21b and miR-146a can discriminate rheumatoid arthritis diagnosis and severity.

Objectives: This study tried to examine the ability of the estimated plasma gene-expression levels (PGEL) of microRNA (miR)-146a and miR-21b to distinguish patients with early rheumatoid arthritis (RA) out of arthritis patients who did not fulfill the diagnostic spectrum of either RA or osteoarthritis (OA); the diagnostic Gray-Zone (GZ).

Patients & methods: Enrolled patients underwent full diagnostic workup and were categorized as highseropositive and fulfilled the diagnostic spectrum for RA (RA-group), seronegative and fulfilling the diagnostic spectrum of OA (OA-group) and low-seropositive or seronegative patients who did not fulfill diagnostic criteria of RA or OA (GZ-group). Blood samples were obtained for quantification of PGEL of miR-146a and miR-21-b using the quantitative Reverse-transcriptase polymerase chain reaction and results were related to patients' seropositivity and clinical data.

Results: The mean fold change of PGEL of miR-146a and miR-21b was significantly higher in patients than in control samples, in samples of high-seropositive patients than in other samples, and in samples of low-seropositive than in seronegative patients. Both markers showed a positive significant correlation with Disease Activity Score-28 for RA-activity and seropositivity. Using the ROC curve analysis, the PGEL of both microRNAs could identify high-seropositive among the studied arthritis patients, but Regression Analysis defined high PGEL of miR-146a as the most significant predictor to identify RA patients and predict their disease activity. Statistical analyses defined miR-146a as the significant parameter that could differentiate between early RA and OA patients among GZ patients.

Conclusion: Early arthritis that does not fulfill the diagnostic spectrum of a certain type of arthritis is not uncommon and challenges therapeutic decision-making. The estimated PGEL of MicroRNA-146a might enlighten this gray diagnostic zone and allow differentiation between patients with early RA and early OA, and help to stratify RA patients according to disease activity and severity.