Investigating the role of exosomal miRNAs in regulating B cell activation andautoantibody production in Malaysian individuals with rheumatoid arthritis

Rheumatoid arthritis (RA) is characterised by the presence of autoantibodies in the serum. Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) are two autoantibodies for diagnosing and classifying RA. Although RF and/or ACPA positivity is present in 50-70% of RA patients, the remaining 30-50% may have low levels of these autoantibodies or be undetectable by either test. The discrepancy in autoantibody levels among RA patients is currently not well understood, making the RA diagnosis more challenging. Based on our preliminary data, it appears that exosomal miRNAs have a significant association with the disease activity of RA patients. However, the mechanisms by which exosomal miRNAs exert their regulatory functions are still unclear. Therefore, our hypothesis is that exosomal miRNAs play a crucial role in regulating B cell activation and controlling the production of undesired autoantibodies from plasma cells. The proposed study aims to identify exosomal miRNAs in specific B-cell subsets derived from peripheral blood mononuclear cells (PBMCs) of RA patients using RNA-seq, and determine their target genes through the use of bioinformatic tools. Additionally, we investigate exosomal miRNAs that are significantly expressed in B cell subsets for their ability to activate B cell proliferation and differentiation using cell proliferation assays and flow cytometry. ELISA is also conducted to measure the production of ACPA before and after the treatment of exosomal miRNAs in B cell subsets. Our findings will provide additional insights into the pathogenesis of RA, and the identified exosomal miRNAs can potentially serve as novel biomarkers to detect the early stages of RA when autoantibody is not detectable. Early detection of RA can lead to early treatment that significantly reduces pain, immobility, and joint deformity, ultimately improving the quality of life for individuals in the Malaysian community.