Genetic immunodeficiency and its association with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovitis, joint destruction, and systemic involvement. Genetic immunodeficiencies, resulting from alterations in genes regulating the immune system, play a role in the pathogenesis of RA. This study aimed to investigate the association between genetic immunodeficiency and RA through a systematic review of scientific articles in PubMed, Scopus, and Web of Science databases. The research method involved searching for articles published between ۲۰۱۰ and ۲۰۲۴ using keywords such as "genetic immunodeficiency and rheumatoid arthritis" and qualitative and quantitative analysis of the data. The findings showed that genes such as HLA-DRB۱ (shared epitope alleles), PTPN۲۲, and STAT۴ increase the risk of RA. These genes contribute to chronic inflammation by disrupting lymphocyte regulation and the production of inflammatory cytokines (TNF-α, IL-۶). For example, HLA-DRB۱ increases the risk up to ۳ times, and PTPN۲۲ is associated with disease severity. Genetic defects also enhance the production of autoantibodies such as RF and ACPA. This article proposes a theory that these defects, beyond being risk factors, are turning points in the pathogenesis of RA and sustain inflammation by creating a positive feedback loop. Mechanisms such as NF-κB hyperactivity and the role of the gut microbiome support this view. The results emphasize the necessity of early diagnosis with genetic testing and targeted therapies (such as IL-۶ inhibitors). Gene therapy is also proposed as a future approach. This study paves the way for better management of RA.

کلیدواژه ها:

Rheumatoid arthritis ، Genetic immunodeficiency ، Immune system ، Targeted therapy