Authors
Yanmei Li, Kairui Zhu, Yushan Ding, Dongyang Wu, Yulong Mu, Xiaoke Liu, Xuelin Liu, Xinran Yu, Yuhan Yan, Yunxiao Sun, Youjie Li
Published in
Frontiers in immunology. Volume 17. Pages 1894263. Epub Jul 20, 2026.
Abstract
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic erosive synovitis, progressive bone destruction, and marked inter-patient heterogeneity in disease course and treatment response. This review critically examines the mechanisms underlying RA immunological heterogeneity, including genetic susceptibility, epigenetic regulation, autoantibody diversification, synovial pathotypes, and gut-joint axis-related immune-metabolic interactions. We further discuss how peripheral blood multi-omics, synovial molecular pathology, and biopsy-driven clinical trial evidence may inform early stratification and prediction of primary non-response. Rather than proposing a deterministic precision-medicine model, this review emphasizes an evidence-weighted framework in which molecular and tissue-level biomarkers are integrated with clinical phenotype and longitudinal treatment response. Emerging approaches, including pharmacomicrobiomics, local drug delivery, nanomedicine, and cell-based therapies, are evaluated as investigational strategies that require further validation. Overall, this review highlights how a more critical understanding of RA heterogeneity may improve patient stratification and support more rational therapeutic selection.
PMID:
42548760
Bibliographic data and abstract were imported from PubMed on 04 Aug 2026.
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