ADVANCES IN POTENTIAL BIOMARKERS FOR RHEUMATOID ARTHRITIS: SYSTEMATIC REVIEW

Abstract

Introduction. Rheumatoid arthritis (RA) is a chronic autoimmune condition marked by continuous inflammation of
the synovial membrane, gradual joint damage and involvement of internal organs. Its relapsing-remitting course leads
to joint deformation, disability and impaired quality of life. The Institute for Health Metrics and Evaluation estimated the
global prevalence of RA to exceed 18 million cases in 2019. Given the multifactorial nature of RA, increasing attention
is being directed to the role of genetic predisposition, autoantibody formation and cytokine dysregulation in disease
onset and progression. Understanding these elements is essential for developing tools for early diagnosis and therap y.
Objective. To analyze current achievements in genetic mutations, autoantibodies, and cytokine profiles involved in
RA pathogenesis and assess their potential for early diagnosis of this disease.
Search Strategy. A systematic review was conducted using PubMed and Google Scholar databases. The search
included full text articles in English, prioritizing peer-reviewed research, systematic review and meta-analysis. Search
terms included “rheumatoid arthritis”, “genetic mutations”, “autoantibodies”, “cytokine production”. Inclusion criteria:
studies focusing on human subjects, evaluating the role of genetic variants, cytokines or autoantibodies in RA
pathogenesis. Exclusion criteria: abstracts without full text, animal studies.
Results. From 1990 to 2024, 33,908 publications on RA were identified, with 4,080 meeting the criteria. The findings
highlight that RA has a multifactorial pathogenesis with a complex genetic background involving both HLA and non-HLA
genes such as HLA-DRB1, STAT4, PADI4 and PTPN22. These gene alterations contribute to T-cell activation, increased
cytokine production, including IL-6, TNF-α and IL-17, and subsequent osteoclast–mediated joint destruction.
Autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies are considered as key diagnostic
biomarkers, often detectable years before the clinical onset of symptoms. Environmental triggers like smoking induce
the formation of autoantibodies, activation of the complement system and sustained synovial inflammation. Together,
these mechanisms underline the diagnostic and prognostic relevance of genetic, cytokine and autoantibody profiling in
RA and support the development of diagnostic and therapeutic approaches.
Conclusion. Genetic susceptibility, cytokine dysregulation and autoantibody production act synergistically in
rheumatoid arthritis, causing joint damage and systemic complications. Emerging biomarkers for RA show considerable
promise in improving early diagnosis, prognosis, and personalized treatment approaches. While several candidates
demonstrate strong potential, further validation and standardization are necessary before widespread clinical
implementation. Continued research will be essential to translate these findings into routine practice.