{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:08:42Z","timestamp":1791223722797,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2007,10,29]],"date-time":"2007-10-29T00:00:00Z","timestamp":1193616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Autoantibodies to citrullinated proteins (ACPAs) are specific for rheumatoid arthritis (RA) and probably are involved in its pathophysiology. Citrullyl residues, posttranslationally generated by peptidyl arginine deiminase (PAD), are indispensable components of ACPA\u2010targeted epitopes. The aim of this study was to identify which PAD isotypes are expressed in the synovial tissue (ST) of patients with RA and are involved in the citrullination of fibrin, the major synovial target of ACPAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Expression of all PAD isotypes, including the recently described PAD type 6 (PAD\u20106), was explored by reverse transcription\u2013polymerase chain reaction and immunoblotting, first in blood\u2010derived mononuclear leukocytes from healthy donors, then in ST samples from 16 patients with RA and 11 control patients (4 with other arthritides and 7 with osteoarthritis [OA]). In ST samples from patients with RA, PADs were localized by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In lymphocytic and monocytic cells and, similarly, in ST samples from patients with RA, the PAD\u20102, PAD\u20104, and PAD\u20106 genes were found to be transcribed, but only PAD\u20102 and PAD\u20104 enzymes were detected. PAD\u20102 was also expressed in ST from control patients, including those with OA, while PAD\u20104 was preferentially expressed in ST from patients with other arthritides. In RA, the expression levels of PAD\u20102 and PAD\u20104 were correlated with the intensity of inflammation (cell infiltration, hypervascularization, and synovial lining hyperplasia), and both enzymes were demonstrable within or in the vicinity of citrullinated fibrin deposits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PAD\u20102 and PAD\u20104 are the only PAD isotypes expressed in the ST of patients with RA and those with other arthritides. Inflammatory cells are a major source, but PAD\u20104 also comes from hyperplastic synoviocytes. Both isotypes are probably involved in the citrullination of fibrin.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22983","type":"journal-article","created":{"date-parts":[[2007,10,29]],"date-time":"2007-10-29T15:54:06Z","timestamp":1193673246000},"page":"3541-3553","source":"Crossref","is-referenced-by-count":348,"title":["Peptidyl arginine deiminase type 2 (PAD\u20102) and PAD\u20104 but not PAD\u20101, PAD\u20103, and PAD\u20106 are expressed in rheumatoid arthritis synovium in close association with tissue 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