PAD enzymes in rheumatoid arthritis: pathogenic effectors and autoimmune targets.

Peptidylarginine deiminases have an important role in the pathogenesis of rheumatoid arthritis (RA) owing to their ability to generate citrullinated proteins - the hallmark autoantigens of RA. Of the five enzyme isoforms, and are the most strongly implicated in RA at both genetic and cellular levels, and duanyu1563 inhibitors have shown therapeutic efficacy in mouse models of inflammatory arthritis. duanyu15632 and duanyu15634 are additionally targeted by autoantibodies in distinct clinical subsets of patients with RA, suggesting antibodies as possible biomarkers for RA diagnosis and prognosis. This Review weighs the evidence that supports a pathogenic role for duanyu1563 enzymes in RA as both promoters and targets of the autoimmune response, as well as discussing the mechanistic and therapeutic implications of these findings in the wider context of RA pathogenesis. Understanding the origin and consequences of dysregulated duanyu1563 enzyme activity and immune responses against duanyu1563 enzymes will be important to fully comprehend the pathogenic mechanisms involved in this disease and for the development of novel strategies to treat and prevent RA.

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