Associations of Plasma Extravesicular (EV) MicroRNA Levels in Seropositive and Seronegative Rheumatoid Arthritis (RA)

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease associated with inflammation. This disease, exacerbated by lower socioeconomic status, disproportionately hinders the quality of life for Hispanic populations. Although the etiology of this disease is still unclear, many speculate the role of epigenetic factors. Among the epigenetic mechanisms proposed to mediate RA are microRNAs (miRNAs). These are a class of small noncoding RNA molecules which predominantly are involved in the post‐transcriptional regulation of gene expression. We hypothesize specific circulating miRNA targets can identify the RA phenotype, and correlate with clinical characteristics of the disease. To test this hypothesis, thirty Hispanic individuals recruited to the Epigenetics of RA (ERA) study samples were investigated. microRNAs were extracted from the serum circulating extracellular vesicles (exosomes) of twenty‐one RA patients and six controls. Levels of 800 miRNA targets were measured blindly using the Nanostring nCounter miRNA Expression Panel and analyzed using nSolver Analysis Software. Five miRNAs (miR‐1261, miR‐4532, miR‐802, miR‐595, miR‐373‐3p) were differentially expressed between seropositive and seronegative RA (p≤0.05). miR‐802 and miR‐1261 positively correlated with ACPA levels (Pearson Coeff.ACPA= 0.608, p=0.001) and ID Pain (Pearson Coeff.ID Pain= 0.472, p=0.041), respectively. No other RA clinical variables were correlated with miRNA levels. Discriminant function analysis identify miR‐1261 (p=0.004) and ACPA (p=0.002) as the strongest biomarkers differentiating seronegative from seropositive RA. We are currently validating these miRNAs associations with RA by qPCR. Understanding which miRNAs play a pivotal role in the etiology of RA in Hispanic patients can provide opportunities to address health disparities in this disease.