EARLY BIOMARKER FOR THE DETECTION OF RHEUMATOID ARTHRITIS USING MIRNA EXPRESSION PROFILING IN WHOLE BLOOD - A CASE CONTROL STUDY

INTRODUCTION: Currently the diagnosis for rheumatoid arthritis is based on the 'The American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) criteria 2010, which ultimately aims at early detection of RA. However, this criterion only gets fullled when nearly more than ten joints are affected, thus giving rise to false negative results in the earlier phases. Early detection and early intervention tends to have better prognosis compared to delayed diagnosis.
Thus a new category of biomarkers which enables early detection is essential. miRNAs are a group of approximately 20 to 22 nucleotides noncoding RNAs, which have been proved to cause regulation of gene expression at the post- transcriptional level. Moreover, when miRNAs are abnormally expressed they can lead to pathological conditions involving the immune system, such as cancer and autoimmunity hence their role as an early biomarker in the diagnosis of RA is evaluated. METHODOLOGY: This is a case control study involving 30 subjects with 15 cases of RA and 15 control age and sex matched healthy subjects. Recently diagnosed RA patients are included and long term treated RA patients are excluded. Peripheral blood analysis was done in both cases and controls by isolating the miRNA, followed by c-DNA synthesis by reverse transcription. Quantication of the miRNA-24, miRNA 125a-5p & miRNA 132 expression in them by real time PCR was done. Statistical analysis was done by Mann Whitney U test and
Spearman correlation to evaluate the statistical signicance of this biomarker in early detection of RA.
RESULTS: The average value of miRNA-24, miRNA-125a-5p and miRNA-132 among the patients recently diagnosed with Rheumatoid Arthritis were 0.745, 1.907 and 0.498 respectively. The average value of miRNA-24, miRNA-125a-5p and miRNA-132 among the healthy controls were 2.548, 0.676 and 0.628 respectively. There were signicant differences (p<0.001) in all three values (miRNA-24, miRNA-125a-5p and miRNA-132) among the two patient groups.
CONCLUSION: The miRNA-24 values were signicantly lower in patients with rheumatoid arthritis when compared healthy controls. The miRNA-125a-5p were signicantly higher in patients with rheumatoid arthritis when compared to healthy controls. The miRNA-132 values were signicantly lower in patients with rheumatoid arthritis when compared to healthy controls. This variation in expression proling and potential role of miRNAs in pathogenesis of rheumatoid arthritis, makes it a potential biomarker for early detection, thereby reducing morbidity and mortality.