Analysis of m6A regulators related immune characteristics in ankylosing spondylitis by integrated bioinformatics and computational strategies

Abstract

AbstractN6-methyladenosine (m6A) modification, as a common epigenetic modification, has been widely studied in autoimmune diseases. However, the role of m6A in the regulation of the immune microenvironment of ankylosing spondylitis (AS) remains unclear. Therefore, we aimed to investigate the effect of m6A modification on the immune microenvironment of AS. We first evaluated RNA modification patterns mediated by 26 m6A regulators in 52 AS samples and 20 healthy samples. Thereafter, an m6A related classifier composed of seven genes was constructed and could effectively distinguish healthy and AS samples. Then, the correlation between m6A regulators and immune characteristics were investigated, including infiltrating immunocytes, immune reactions activity, and human leukocyte antigen (HLA) genes expression. The results indicated that m6A regulators was closely correlated with immune characteristics. For example, EIF3A was significantly related to infiltrating immunocytes; IGF2BP2 and EIF3A were significant regulators in immune reaction of TGF-β family member, and the expression of HLA-DPA1 and HLA-E were affected by EIF3A and ALKBH5. Next, two distinct m6A expression patterns were identified through unsupervised clustering analysis, and diverse immune characteristics were found between them. A total of 5889 m6A phenotype-related genes were obtained between the two expression patterns, and their biological functions were revealed. Finally, we validated the expression status of m6A modification regulators using two additional datasets. Our findings illustrate that m6A modifications play a critical role in the diversity and complexity of the AS immune microenvironment.