Differential Gene Expression in Rheumatoid Arthritis: Implication in the Diagnosis and Individualized Treatment Plan

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and destruction of the joints due to the involvement of biologic, environmental, and genetic factors. Due to its pathogenesis being multifactorial in origin, the underlying molecular mechanisms contributing to the development of RA remain unclear. Therefore, understanding the factors driving RA is crucial for developing targeted therapies and improving patient outcomes. With various genetic variants contributing to RA, this article explores the role of differential gene expression in patients with RA and in different ethnic populations and how the genes contribute to RA susceptibility. Key takeaways from this review demonstrate how HLA shared epitope alleles and non-HLA genes have a strong association with RA and play an important role in immune regulation, autoantibody production, cytokine production, and development of extra-articular manifestations observed in RA. Additionally, gene expression in RA can vary across different sexes and ethnic populations, emphasizing the importance of developing personalized therapeutic interventions. These findings provide insight into the role of differential gene expression in improving diagnostic and therapeutic strategies and highlights potential therapeutic targets for RA management. Future research is needed to determine the clinical relevance of differential gene expression in developing interventions for RA treatment.

Keywords: Autoantibodies; Differential gene expression; Disease-modifying antirheumatic drugs; HLA-DRB1 alleles; Inflammation; Methotrexate; Rheumatoid arthritis; Single nucleotide polymorphism.

Figure 1:

Prevalence of Rheumatoid Arthritis. Worldwide prevalence versus higher prevalence in certain demographics, doubling in Australia, and up to 6.8-fold in Native American tribes such as the Chippewa.

Figure 2:

Overview of Underlying Mechanisms of Rheumatoid Arthritis. This illustration demonstrates the various mechanisms contributing to the pathogenesis of RA, including signaling pathways (NF-kB, JAK-STAT, MAPK), fibroblast-like synoviocytes, innate and adaptive immunity, autoantibodies, cytokines, genetics, and environmental factors.

Figure 3:

Therapeutics for Rheumatoid Arthritis. This flow chart provides an overview of selected short-term and long-term thematic options for treatment of rheumatoid arthritis.