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• W2938775368 abstract "In the late 1990s, the discovery that citrullinated proteins are targeted by autoantibodies known as anti-citrullinated protein antibodies (ACPA) revolutionised the study of rheumatoid arthritis (RA). Because of the high specificity of ACPA for RA, investigators began experiments to determine whether ACPA have a direct pathogenetic role in arthritis or whether these antibodies more simply reflect underlying T-cell and B-cell responses without themselves impacting on joint inflammation and damage. The debate on the role of ACPA has been extensive and has now entered a new phase with the publication of correction notes appearing in this issue1 2 of Annals of the Rheumatic (ARD ). These notes concern papers that appeared in the journal in 20163 4 and follow a retraction note and correspondence in other journals.5–7 In these notes, the study authors indicate that the monoclonal antibodies used in their experiments on ACPA pathogenicity did not, in fact, react with citrullinated proteins and/or peptides. As such, the putative functional activities of these monoclonals must have resulted from mechanisms other than antibody binding to a citrullinated target. The implications of these corrections and retractions for models of pathogenesis are wide ranging and call into question the nature of ACPA involvement in manifestations of RA. Because of the importance of these issues for the scientific community, in this editorial, we will review the role of ACPA in RA and the salient issues in establishing the pathogenicity of these autoantibodies.ACPA are unique biomarkers for RA, a serious form of arthritis characterised by inflammation, pain and, unless treated effectively, damage of cartilage and bone. As shown in elegant biochemical studies, ACPA target proteins that contain the amino acid citrulline, a post-translational modification (PTM) of the amino acid arginine mediated by peptidyl arginine deiminase enzymes8 9; these antibodies are also …" @default.
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• W2938775368 date "2019-04-20" @default.
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• W2938775368 title "Pathogenic effector functions of ACPA: Where do we stand?" @default.
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• W2938775368 doi "https://doi.org/10.1136/annrheumdis-2019-215337" @default.
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