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However, an entire profile of and autoimmunity of the citrullinated proteins have been poorly understood. To understand the profile, we examined citrullinated autoantigens by a proteomic approach and further investigated the significance of citrullination in antigenicity of one of the autoantigens. Specifically, we detected citrullinated autoantigens in synovial tissue of a patient with RA by two-dimensional electrophoresis and Western blotting by using pooled sera from five patients with RA and anti-citrulline antibodies. After identifying the detected autoantigens by mass spectrometry, we investigated the contribution of citrullination to autoantigenicity by using a recombinant protein with or without citrullination on one of the identified novel citrullinated autoantigens. As a result, we found 51 citrullinated protein spots. Thirty (58.8%) of these spots were autoantigenic. We identified 13 out of the 30 detected citrullinated autoantigenic proteins. They contained three fibrinogen derivatives and several novel citrullinated autoantigens (for example, asporin and F-actin capping protein \u03b1-1 subunit [CapZ\u03b1-1]). We further analyzed the contribution of citrullination to autoantigenicity in one of the detected citrullinated autoantigens, CapZ\u03b1-1. As a result, frequencies of autoantibodies to non-citrullinated CapZ\u03b1-1 were 36.7% in the RA group tested, 10.7% in the osteoarthritis (OA) group, and 6.5% in healthy donors. On the other hand, those to citrullinated CapZ\u03b1-1 were 53.3% in the RA group, 7.1% in the OA group, and 6.5% in the healthy donors. This shows that autoantigenicity of citrullinated or non-citrullinated CapZ\u03b1-1 is relevant to RA. The antibody titers to the citrullinated CapZ\u03b1-1 were significantly higher than those to the non-citrullinated CapZ\u03b1-1 in 36.7% of patients; however, the other patients showed almost equal antibody titers to both citrullinated and non-citrullinated CapZ\u03b1-1. Therefore, the autoantibodies would target citrulline-related and\/or citrulline-unrelated epitope(s) of CapZ\u03b1-1. In conclusion, we report a profile of citrullinated autoantigens for the first time. Even though citrullination is closely related to autoantigenicity, citrullination would not always produce autoantigenicity in RA. Citrullinated and non-citrullinated autoantigens\/autoepitopes would have different pathological roles in RA.<\/jats:p>","DOI":"10.1186\/ar2085","type":"journal-article","created":{"date-parts":[[2006,11,28]],"date-time":"2006-11-28T07:32:06Z","timestamp":1164699126000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":118,"title":["Identification of novel citrullinated autoantigens of synovium in rheumatoid arthritis using a proteomic approach"],"prefix":"10.1186","volume":"8","author":[{"given":"Kosuke","family":"Matsuo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayo","family":"Masuko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Yudoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Noyori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kusuki","family":"Nishioka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2006,11,27]]},"reference":[{"key":"1950_CR1","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1136\/ard.60.1.49","volume":"60","author":"T Sekine","year":"2001","unstructured":"Sekine T, Masuko-Hongo K, Matsui T, Asahara H, Takigawa M, Nishioka K, Kato T: Recognition of YKL-39, a human cartilage related protein, as a target antigen in patients with rheumatoid arthritis. 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