Epigenetic Changes in the Pathogenesis of Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects about 1% of the world’s population. The etiology of RA remains unknown. It is considered to occur in the presence of genetic and environmental factors. An increasing body of evidence pinpoints that epigenetic modifications play an important role in the regulation of RA pathogenesis. Epigenetics causes heritable phenotype changes that are not determined by changes in the DNA sequence. The major epigenetic mechanisms include DNA methylation, histone proteins modifications and changes in gene expression caused by microRNAs and other non-coding RNAs. These modifications are reversible and could be modulated by diet, drugs, and other environmental factors. Specific changes in DNA methylation, histone modifications and abnormal expression of non-coding RNAs associated with RA have already been identified. This review focuses on the role of these multiple epigenetic factors in the pathogenesis and progression of the disease, not only in synovial fibroblasts, immune cells, but also in the peripheral blood of patients with RA, which clearly shows their high diagnostic potential and promising targets for therapy in the future.

Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response

“…Recently, the results of a GWAS—a study aimed to determine personalised RA therapy based on the genetic polymorphisms associated with sensitivity to FDA-approved antirheumatic drugs—have been published. Moreover, epigenetic changes (including microRNA polymorphism and expression) altering the disease complication risk and response to treatment should be taken to account, along with the germline variants assessment for RA predisposition and therapy response [ 96 , 97 ]. In that way, researchers are striving to develop a genetic testing algorithm for DMARD therapy personalisation to make RA treatment more clinically- and cost-effective.…”

Emerging Concepts and Challenges in Rheumatoid Arthritis Gene Therapy

“…It is also possible to induce demethylation of methylated cytosine (5mC) at CpG sites and revert histone modifications [119]. At the same time, it is hardly conceivable to identify a sole target for RA treatment, because multiple epigenetic factors acting in distinct cells are collectively involved in the pathogenesis and progression of the disease [4]. To the best of our knowledge, there have been no experimental studies on RA treatment via genome or epigenome editing.…”

“…Rheumatoid arthritis (RA) is an autoimmune disease that affects about 1% of the world's population [2,3]. The main problem in RA treatment is that the exact causes of the disease are unknown [4]. Obviously, a genetic predisposition is among the major factors, because the prevalence varies in different populations.…”

Prediction of Self-Perception of Patient in Rheumatoid Arthritis With the Key RNAs Expression Profiles

“…There is a clear genetic basis to RA but its underlying mechanisms remain unknown (9). Recently, an increasing number of studies have attempted to reveal the important role of epigenetics in the pathogenesis of RA (10,11). Circular RNAs (circRNAs) and long non-coding RNA (lncRNA), a novel type of endogenous non-coding RNA recently rediscovered (12,13), are known to modulate the activity of interacting proteins or act as miRNA sponges.…”