Reduced expression of miRNAs as potential biomarkers in axial spondyloarthritis.

OBJECTIVE: This study aimed to investigate the value of miR-29a-3p, miR-27a, miR126-3p, miR-146a-5p, miR-625-3p, miR-130a, miR-32, miR-218, miR-131, and miR5196 in the diagnosis of axial spondyloarthritis and to determine whether there is a difference in miRNA expression levels between radiographic axial spondyloarthritis and non-radiographic axial spondyloarthritis, as well as the relationship between miRNA expression levels, disease activity, and uveitis history. METHODS: This study included 50 patients with axial spondyloarthritis (25 with radiographic axial spondyloarthritis and 25 with non-radiographic axial spondyloarthritis) and 25 healthy individuals. The fold change of miRNA expression for each miRNA was calculated using the 2-ΔΔCt method. RESULTS: The expression of all miRNAs except miR-130a was downregulated in axial spondyloarthritis patients (miR-27a: fold regulation: -11.21, p<0.001; miR-29a-3p: fold regulation: -2.63, p<0.001; miR-32: fold regulation: -2.94, p=0.002; miR-126-3p: fold regulation -10.94, p<0.001; miR-132: fold regulation: -2.18, p<0.001; miR-146-5p: fold regulation: -9.78, p<0.001; miR-218: fold regulation: -2.65, p<0.001; miR-625-3p: fold regulation: -2.01, p=0.001; miR-5196-3p: fold regulation: -7.04, p<0.001). The expression levels of these miRNAs did not differ significantly between non-radiographic axial spondyloarthritis and radiographic axial spondyloarthritis patients (p>0.05 for all). CONCLUSION: Particularly, miR-27a, miR-126-3p, miR-146-5p, and miR-5196-3p were found to be substantially downregulated in both non-radiographic axial spondyloarthritis and radiographic axial spondyloarthritis patients, suggesting their potential as diagnostic biomarkers for axial spondyloarthritis.

Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific.

Objectives: To find out the genetic association between IL6 and autoimmune arthritis. Methods: We performed a two-sample Mendelian randomization (MR) study using multiple genome-wide association studies (GWAS) datasets. Furthermore, a sex-stratified MR study was performed to identify sexual dimorphism in the association between IL6 and autoimmune arthritis. Then, LocusZoom plots were displayed based on the IL6R gene region to present evidence of genetic colocalization between diseases. Results: The MR result denoted a genetic association between the increased level of IL-6 signaling and risk of RA (ß=0.325, 95%CI 0.088, 0.561, p=7.08E-03) and AS (ß=1.240, 95%CI 0.495, 1.980, p=1.1E-03). Accordingly, sIL6R was found to have negatively correlation with the onset of RA (ß=-0.020, 95%CI -0.0320, -0.008, p=1.18E-03) and AS (ß=-0.125, 95%CI -0.177, -0.073, p=2.29E-06). However, no genetic association between IL6/sIL6R and PsA was detected. The gender-stratified MR analysis showed that IL6 was associated with AS in the male population, with RA in the female population, and with PsA in the male population. Additionally, ADAR, a gene identified by a sensitive test, could be the reason for the nonsignificant association between IL6 and PsA in a pooled population. Conclusion: Our findings showed that the overactive IL6 signal pathway led to autoimmune arthritis, especially in RA and AS. Sexual difference was also observed in IL6-intermediate susceptibility to autoimmune arthritis.