Inflammatory Arthritis (IA) constitutes a diverse range of autoimmune conditions sharing characteristic features including soft tissue swelling, joint inflammation and subsequent bone and cartilage destruction of a debilitating nature. Unfortunately, the prevalence of IA in Ireland is 1-2%, of which Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA) encompass two of the most common forms. While common pathogenic mechanisms are involved in driving inflammation in both arthropathies there are significant differences, including the presence/absence of autoantibodies, synovial vascularity, presence of skin psoriasis, immune cell infiltrates, molecular signalling, the pattern of periarticular inflammation, bone erosion and new bone formation at the entheseal complex of peripheral and spinal joints. These differences may explain distinct clinical manifestations of the two diseases, and more importantly, explain different responses to specific therapies impacting on disease outcomes and prognoses. While there are common treatments that are utilised as first line treatment for RA and PsA, including methotrexate and tumor necrosis factor inhibitors (TNFi), their response to other biologic therapies differs, with Rituximab and anti-IL-6R only utilised for treatment of RA, while anti-IL-17A and anti- IL-12/IL23 are utilised for PsA. Furthermore, the multifaceted nature of synovial inflammation, joint destruction, enthesitis, axial disease, and skin manifestations often makes diagnosis, prediction of disease progression and prediction of response difficult. However, currently there are few biomarkers that distinguish disease pathotype or response to therapy. Thus there is a need for the identification of noninvasive, convenient, and reliable biomarkers for the diagnosis and prediction of treatment response outcomes in autoimmune disease.
‘MicroRNA (miRNA)’ which are small endogenous regulatory RNA molecules have emerged as potential therapeutic targets and biomarkers in autoimmunity. MiRNA bind to complementary sequences on messenger RNA (mRNA), and they function generally by suppressing the translation of target proteins (Figure 1A). In the context of Inflammatory Arthritis, their effects generally down regulate proteins involved in keeping the immune response in-check, thus once unchecked this allows for an uncontrolled immune response which leads to cartilage study hasdemonstratedthe potentialfor serummiRNAs to beinstrumentalin a diagnosticcapacity in aclinical setting”degradation and bone erosions. Over the last 10 years numerous studies have demonstrated that altered miRNA expression in Inflammatory Arthritis influences immune cell regulation, enhances pro-inflammatory signaling pathways, and leads to the overproduction of proinflammatory proteins that are critical to driving the pathogenic mechanisms involved in joint destruction and subsequent joint disability. However, more recent studies have identified that, in addition to their localization within the cell, miRNAs are also present in extracellular fluids such as serum, plasma, and synovial fluid, and through the circulation can be transported to specific cell types or tissues to carry out their function. Interestingly, it is now known that circulatory miRNAs are more stable than cellular miRNAs and are emerging as potential non-invasive biomarkers for disease.
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