{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:23:05Z","timestamp":1791141785440,"version":"4.1.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"16","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1995,8]]},"abstract":"<jats:p>We identified an autoantibody that reacts with calpastatin [an inhibitor protein of the calcium-dependent neutral protease calpain (EC 3.4.22.17)]. In early immunoblot studies, sera from patients with rheumatoid arthritis (RA) recognized unidentified 60-, 45-, and 75-kDa proteins in HeLa cell extracts. To identify these autoantigens, we used patient sera to clone cDNAs from a lambda gt11 expression library. We isolated clones of four genes that expressed fusion proteins recognized by RA sera. The 1.2-kb cDNA insert (termed RA-6) appeared to encode a polypeptide corresponding to the 60-kDa antigen from HeLa cells, since antibodies bound to the RA-6 fusion protein also reacted with a 60-kDa HeLa protein. The deduced amino acid sequence of the RA-6 cDNA was completely identical with the C-terminal 178 amino acids of human calpastatin except for one amino acid substitution. Patient sera that reacted with the RA-6 also bound pig muscle calpastatin, and a monoclonal antibody to human calpastatin recognized the RA-6 fusion protein, confirming the identity of RA-6 with calpastatin. Moreover, the purified RA-6 fusion protein inhibited the proteolytic activity of calpain, and IgG from a serum containing anti-calpastatin antibodies blocked the calpastatin activity of the RA-6 fusion protein. Immunoblots of the RA-6 product detected autoantibodies to calpastatin in 57% of RA patients; this incidence was significantly higher than that observed in other systemic rheumatic diseases, including systemic lupus erythematosus (27%), polymyositis\/dermatomyositis (24%), systemic sclerosis (38%), and overlap syndrome (29%). Thus, anti-calpastatin antibodies are present most frequently in patients with RA and may participate in pathogenic mechanisms of rheumatic diseases.<\/jats:p>","DOI":"10.1073\/pnas.92.16.7267","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T09:17:14Z","timestamp":1149067034000},"page":"7267-7271","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":52,"title":["Autoantibodies to calpastatin (an endogenous inhibitor for calcium-dependent neutral protease, calpain) in systemic rheumatic diseases."],"prefix":"10.1073","volume":"92","author":[{"given":"T","family":"Mimori","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Suganuma","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Tanami","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Nojima","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Yoshizawa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Akizuki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1995,8]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.92.16.7267","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:08:06Z","timestamp":1649858886000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.92.16.7267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,8]]},"references-count":0,"journal-issue":{"issue":"16","published-print":{"date-parts":[[1995,8]]}},"alternative-id":["10.1073\/pnas.92.16.7267"],"URL":"https:\/\/doi.org\/10.1073\/pnas.92.16.7267","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,8]]},"assertion":[{"value":"1995-08-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}