Integrated analysis of m6A regulator-mediated RNA methylation modification patterns and immune characteristics in Sjögren’s Syndrome

Abstract

Abstract Growing evidence suggests that N6-methyladenosine (m6A), the most abundant RNA internal modification, plays a critical role in immune regulation and thereby potentially contributes to the pathogenesis of autoimmune disorders. However, the role of m6A modification of the immune microenvironment of Sjögren’s syndrome (SS) remains unknown. In this study, we used data from public databases and our sequencing efforts to evaluate the expression levels of m6A regulators by profiling the data of whole peripheral blood of 220 SS patients and 62 healthy controls. We found that SS was associated with the expression of several m6A regulators, and this difference was correlated with activated CD4+T cells. We screened key genes with a random forest (RF) machine learning algorithm and constructed a diagnostic model of SS using multivariate logistic regression analysis. Two distinct m6A modification patterns were determined by unsupervised clustering, with significant differences in immunocyte infiltration, immune reactivity, and enriched biological functions. Key m6A regulators, gene modules, and co-expression networks of m6A-related genes were identified by conventional bioinformatics methods. This identified three key m6A regulators (METTL3, ALKBH5, and YTHDF1) and two m6A-related hub genes (COMMD8 and SRP9) which may play an essential role in the diagnosis and treatment of SS. This study demonstrates the close relationship between m6A modification and the immune microenvironment in SS and provides a basis for an improved understanding of m6A modification patterns and the exploration of new therapeutic options for SS.