ACPA-negative rheumatoid arthritis: From immune mechanisms to clinical translation
Ketian Li,
Min Wang,
Lidan Zhao,
Yudong Liu,
Xuan Zhang
Affiliations
Ketian Li
Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, PR China
Min Wang
Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, PR China
Lidan Zhao
Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, PR China
Yudong Liu
Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, PR China; The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, PR China; Corresponding authors at: Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Xuan Zhang
Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, PR China; Corresponding authors at: Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Summary: The presence of anti-citrullinated protein autoantibodies (ACPA) is a hallmark feature of rheumatoid arthritis (RA), which causes chronic joint destruction and systemic inflammation. Based on ACPA status, RA patients can be sub-grouped into two major subsets: ACPA-positive RA (ACPA+ RA) and ACPA-negative RA (ACPA– RA). Accumulating evidence have suggested that ACPA+ RA and ACPA– RA are two distinct disease entities with different underlying pathophysiology. In contrast to the well-characterized pathogenic mechanisms of ACPA+ RA, the etiology of ACPA– RA remains largely unknown. In this review, we summarized current knowledge about the primary drivers of ACPA– RA, particularly focusing on the serological, cellular, and molecular aspects of immune mechanisms. A better understanding of the immunopathogenesis in ACPA– RA will help in designing more precisely targeting strategies, and paving the road to personalized treatment. In addition, identification of novel biomarkers in ACPA– RA will substantially promote early treatment and improve the outcomes.