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Identification of novel citrullinated autoantigens of synovium in rheumatoid arthritis using a proteomic approach

Recently, autoantibodies to some citrullinated autoantigens have been reported to be specific for rheumatoid arthritis (RA). However, an entire profile of and autoimmunity of the citrullinated proteins have been poorly understood. To understand the profile, we examined citrullinated autoantigens by...

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Autores principales: Matsuo, Kosuke, Xiang, Yang, Nakamura, Hiroshi, Masuko, Kayo, Yudoh, Kazuo, Noyori, Koji, Nishioka, Kusuki, Saito, Tomoyuki, Kato, Tomohiro
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1794520/
https://www.ncbi.nlm.nih.gov/pubmed/17125526
http://dx.doi.org/10.1186/ar2085
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author Matsuo, Kosuke
Xiang, Yang
Nakamura, Hiroshi
Masuko, Kayo
Yudoh, Kazuo
Noyori, Koji
Nishioka, Kusuki
Saito, Tomoyuki
Kato, Tomohiro
author_facet Matsuo, Kosuke
Xiang, Yang
Nakamura, Hiroshi
Masuko, Kayo
Yudoh, Kazuo
Noyori, Koji
Nishioka, Kusuki
Saito, Tomoyuki
Kato, Tomohiro
author_sort Matsuo, Kosuke
collection PubMed
description Recently, autoantibodies to some citrullinated autoantigens have been reported to be specific for rheumatoid arthritis (RA). 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 α-1 subunit [CapZα-1]). We further analyzed the contribution of citrullination to autoantigenicity in one of the detected citrullinated autoantigens, CapZα-1. As a result, frequencies of autoantibodies to non-citrullinated CapZα-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 CapZα-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 CapZα-1 is relevant to RA. The antibody titers to the citrullinated CapZα-1 were significantly higher than those to the non-citrullinated CapZα-1 in 36.7% of patients; however, the other patients showed almost equal antibody titers to both citrullinated and non-citrullinated CapZα-1. Therefore, the autoantibodies would target citrulline-related and/or citrulline-unrelated epitope(s) of CapZα-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.
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spelling pubmed-17945202007-02-08 Identification of novel citrullinated autoantigens of synovium in rheumatoid arthritis using a proteomic approach Matsuo, Kosuke Xiang, Yang Nakamura, Hiroshi Masuko, Kayo Yudoh, Kazuo Noyori, Koji Nishioka, Kusuki Saito, Tomoyuki Kato, Tomohiro Arthritis Res Ther Research Article Recently, autoantibodies to some citrullinated autoantigens have been reported to be specific for rheumatoid arthritis (RA). 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 α-1 subunit [CapZα-1]). We further analyzed the contribution of citrullination to autoantigenicity in one of the detected citrullinated autoantigens, CapZα-1. As a result, frequencies of autoantibodies to non-citrullinated CapZα-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 CapZα-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 CapZα-1 is relevant to RA. The antibody titers to the citrullinated CapZα-1 were significantly higher than those to the non-citrullinated CapZα-1 in 36.7% of patients; however, the other patients showed almost equal antibody titers to both citrullinated and non-citrullinated CapZα-1. Therefore, the autoantibodies would target citrulline-related and/or citrulline-unrelated epitope(s) of CapZα-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. BioMed Central 2006 2006-11-27 /pmc/articles/PMC1794520/ /pubmed/17125526 http://dx.doi.org/10.1186/ar2085 Text en Copyright © 2006 Matsuo et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Matsuo, Kosuke
Xiang, Yang
Nakamura, Hiroshi
Masuko, Kayo
Yudoh, Kazuo
Noyori, Koji
Nishioka, Kusuki
Saito, Tomoyuki
Kato, Tomohiro
Identification of novel citrullinated autoantigens of synovium in rheumatoid arthritis using a proteomic approach
title Identification of novel citrullinated autoantigens of synovium in rheumatoid arthritis using a proteomic approach
title_full Identification of novel citrullinated autoantigens of synovium in rheumatoid arthritis using a proteomic approach
title_fullStr Identification of novel citrullinated autoantigens of synovium in rheumatoid arthritis using a proteomic approach
title_full_unstemmed Identification of novel citrullinated autoantigens of synovium in rheumatoid arthritis using a proteomic approach
title_short Identification of novel citrullinated autoantigens of synovium in rheumatoid arthritis using a proteomic approach
title_sort identification of novel citrullinated autoantigens of synovium in rheumatoid arthritis using a proteomic approach
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1794520/
https://www.ncbi.nlm.nih.gov/pubmed/17125526
http://dx.doi.org/10.1186/ar2085
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