{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:27:59Z","timestamp":1792063679361,"version":"4.4.0"},"reference-count":177,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T00:00:00Z","timestamp":1591228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005795","name":"Chang Gung Memorial Hospital, Linkou","doi-asserted-by":"publisher","award":["CMRPG1H0101"],"award-info":[{"award-number":["CMRPG1H0101"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Individuals with high anti-citrullinated protein antibody (ACPA) titers have an increased risk of developing rheumatoid arthritis (RA). Although our knowledge of the generation and production of ACPAs has continuously advanced during the past decade, our understanding on the pathogenic mechanisms of how ACPAs interact with immune cells to trigger articular inflammation is relatively limited. Citrullination disorders drive the generation and maintenance of ACPAs, with profound clinical significance in patients with RA. The loss of tolerance to citrullinated proteins, however, is essential for ACPAs to exert their pathogenicity. N-linked glycosylation, cross-reactivity and the structural interactions of ACPAs with their citrullinated antigens further direct their biological functions. Although questions remain in the pathogenicity of ACPAs acting as agonists for a receptor-mediated response, immune complex (IC) formation, complement system activation, crystallizable fragment gamma receptor (Fc\u03b3R) activation, cross-reactivity to joint cartilage and neutrophil extracellular trap (NET)-related mechanisms have all been suggested recently. This paper presents a critical review of the characteristics and possible biological effects and mechanisms of the immunopathogenesis of ACPAs in patients with RA.<\/jats:p>","DOI":"10.3390\/ijms21114015","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T03:32:21Z","timestamp":1591327941000},"page":"4015","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Anti-Citrullinated Protein Antibodies in Patients with Rheumatoid Arthritis: Biological Effects and Mechanisms of Immunopathogenesis"],"prefix":"10.3390","volume":"21","author":[{"given":"Chao-Yi","family":"Wu","sequence":"first","affiliation":[{"name":"Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"},{"name":"Chang Gung University, College of Medicine, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6826-9717","authenticated-orcid":false,"given":"Huang-Yu","family":"Yang","sequence":"additional","affiliation":[{"name":"Chang Gung University, College of Medicine, Taoyuan 333, Taiwan"},{"name":"Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6266-705X","authenticated-orcid":false,"given":"Jenn-Haung","family":"Lai","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Graduate Institute of Medical Science, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N. 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