Current state and future directions of basic research in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Despite advances in biologic therapies targeting inflammatory mediators such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, Janus kinase (JAK), and B cells, many patients do...

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Main Authors: Byeongzu Ghang, Jin Kyun Park, Ji Hyeon Ju, Seungwoo Han
Format: Article
Language:English
Published: Korean College of Rheumatology 2025-07-01
Series:Journal of Rheumatic Diseases
Subjects:
Online Access:http://www.jrd.or.kr/journal/view.html?doi=10.4078/jrd.2024.0151
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author Byeongzu Ghang
Jin Kyun Park
Ji Hyeon Ju
Seungwoo Han
author_facet Byeongzu Ghang
Jin Kyun Park
Ji Hyeon Ju
Seungwoo Han
author_sort Byeongzu Ghang
collection DOAJ
description Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Despite advances in biologic therapies targeting inflammatory mediators such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, Janus kinase (JAK), and B cells, many patients do not respond adequately, emphasizing the need for deeper insights into RA pathogenesis. Research highlights the intricate interplay of genetic and epigenetic factors driving immune dysregulation. The breakdown of immune tolerance, often initiated in mucosal sites such as the gut, lung, and oral cavity, promotes the citrullination of antigens, leading to anti-citrullinated protein antibody production and subsequent immune activation. Single-cell and multiomics approaches have shed light on underexplored immune cell types, such as T peripheral helper cells, CD4+/CD8+ cytotoxic T cells, and autoreactive B cells, broadening the understanding beyond traditionally studied Th17, Th1 cells, macrophages, and fibroblast-like synoviocytes. Future basic research in RA should prioritize elucidating the mechanisms behind peripheral tolerance breakdown, the pathogenesis of seronegative RA, and the molecular pathways driving refractory and recurrent disease. Moreover, leveraging multi-omics approaches to dissect disease heterogeneity will be pivotal for advancing personalized treatment strategies and improving long-term outcomes in RA patients.
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spelling doaj-art-4da5b42faaf3484fae2b3ba9dd74bb852025-08-20T03:27:43ZengKorean College of RheumatologyJournal of Rheumatic Diseases2093-940X2025-07-0132316618110.4078/jrd.2024.0151jrd.2024.0151Current state and future directions of basic research in rheumatoid arthritisByeongzu Ghang0Jin Kyun Park1Ji Hyeon Ju2Seungwoo Han3Division of Rheumatology, Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, KoreaDivision of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, KoreaSeoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, KoreaSchool of Medicine, Kyungpook National University, Daegu, KoreaRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Despite advances in biologic therapies targeting inflammatory mediators such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, Janus kinase (JAK), and B cells, many patients do not respond adequately, emphasizing the need for deeper insights into RA pathogenesis. Research highlights the intricate interplay of genetic and epigenetic factors driving immune dysregulation. The breakdown of immune tolerance, often initiated in mucosal sites such as the gut, lung, and oral cavity, promotes the citrullination of antigens, leading to anti-citrullinated protein antibody production and subsequent immune activation. Single-cell and multiomics approaches have shed light on underexplored immune cell types, such as T peripheral helper cells, CD4+/CD8+ cytotoxic T cells, and autoreactive B cells, broadening the understanding beyond traditionally studied Th17, Th1 cells, macrophages, and fibroblast-like synoviocytes. Future basic research in RA should prioritize elucidating the mechanisms behind peripheral tolerance breakdown, the pathogenesis of seronegative RA, and the molecular pathways driving refractory and recurrent disease. Moreover, leveraging multi-omics approaches to dissect disease heterogeneity will be pivotal for advancing personalized treatment strategies and improving long-term outcomes in RA patients.http://www.jrd.or.kr/journal/view.html?doi=10.4078/jrd.2024.0151rheumatoid arthritisanti-citrullinated protein antibodysynovial inflammationimmune dysregulationdisease heterogeneity
spellingShingle Byeongzu Ghang
Jin Kyun Park
Ji Hyeon Ju
Seungwoo Han
Current state and future directions of basic research in rheumatoid arthritis
Journal of Rheumatic Diseases
rheumatoid arthritis
anti-citrullinated protein antibody
synovial inflammation
immune dysregulation
disease heterogeneity
title Current state and future directions of basic research in rheumatoid arthritis
title_full Current state and future directions of basic research in rheumatoid arthritis
title_fullStr Current state and future directions of basic research in rheumatoid arthritis
title_full_unstemmed Current state and future directions of basic research in rheumatoid arthritis
title_short Current state and future directions of basic research in rheumatoid arthritis
title_sort current state and future directions of basic research in rheumatoid arthritis
topic rheumatoid arthritis
anti-citrullinated protein antibody
synovial inflammation
immune dysregulation
disease heterogeneity
url http://www.jrd.or.kr/journal/view.html?doi=10.4078/jrd.2024.0151
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AT jihyeonju currentstateandfuturedirectionsofbasicresearchinrheumatoidarthritis
AT seungwoohan currentstateandfuturedirectionsofbasicresearchinrheumatoidarthritis