{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:23:08Z","timestamp":1791062588327,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2004,10,7]],"date-time":"2004-10-07T00:00:00Z","timestamp":1097107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,10,7]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n               <jats:p>Systemic sclerosis (SSc) is characterized by multi-organ fibrosis with an autoimmune background. Although autoantibodies are detected frequently in SSc patients, the role of autoantibody in the development of fibrosis remains unknown. Connective tissue homeostasis is a balance between the synthesis and degradation of the extracellular matrix (ECM); ECM degradation is regulated mainly by matrix metalloproteinases (MMPs). Anti-MMP-1 antibody is suggested to inhibit MMP-1 and be involved in the development of the fibrosis in SSc. However, the accumulation of various ECM components in the tissue of SSc cannot be explained by the anti-MMP-1 antibody alone. In this study, we examined the presence\u200a or\u200a levels of antibody to MMP-3, a protein which degrades various ECM components relevant to SSc fibrosis. Enzyme-linked immunosorbent assay (ELISA) using human recombinant MMP-3 revealed that IgG anti-MMP-3 autoantibody levels were elevated significantly in the sera from SSc patients, but not in patients with active systemic lupus erythematosus or dermatomyositis. IgG and IgM anti-MMP-3 antibody levels were significantly higher in diffuse cutaneous SSc, a severe form, than those in limited cutaneous SSc. Consistently, IgG anti-MMP-3 antibody levels correlated significantly with fibrosis of the skin, lung and renal blood vessels. The presence of IgG anti-MMP-3 autoantibody in sera from SSc patients was confirmed by immunoblotting analysis. Remarkably, MMP-3 activity was inhibited by IgG anti-MMP-3 antibody. These results suggest that anti-MMP-3 antibody is a serological marker that reflects the severity of SSc and also suggest that it may contribute to the development of fibrosis by inhibiting MMP-3 activity and reducing the ECM turnover.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2004.02615.x","type":"journal-article","created":{"date-parts":[[2004,10,20]],"date-time":"2004-10-20T11:44:23Z","timestamp":1098272663000},"page":"357-363","source":"Crossref","is-referenced-by-count":80,"title":["Autoantibody against matrix metalloproteinase-3 in patients with systemic sclerosis"],"prefix":"10.1093","volume":"138","author":[{"given":"C","family":"NISHIJIMA","sequence":"first","affiliation":[{"name":"Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"HAYAKAWA","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"MATSUSHITA","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"KOMURA","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"HASEGAWA","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"TAKEHARA","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"SATO","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,10,20]]},"reference":[{"key":"2022010901430749000_b1","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/S0889-857X(05)70294-5","article-title":"Pathogenesis of scleroderma","volume":"22","author":"Jimenez","year":"1996","journal-title":"Collagen Rheum Dis Clin North Am"},{"key":"2022010901430749000_b2","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/j.1365-2133.1979.tb01635.x","article-title":"Characterization of dermal collagen in systemic sclerosis","volume":"100","author":"Lovell","year":"1979","journal-title":"Br J Dermatol"},{"key":"2022010901430749000_b3","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1172\/JCI107827","article-title":"Increased collagen synthesis by scleroderma skin fibroblasts in vitro: a possible defect in the regulation or activation of the scleroderma fibroblast","volume":"54","author":"LeRoy","year":"1974","journal-title":"J Clin Invest"},{"key":"2022010901430749000_b4","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1002\/art.1780331211","article-title":"Increased expression of type VI collagen genes in systemic sclerosis","volume":"33","author":"Peltonen","year":"1990","journal-title":"Arthritis Rheum"},{"key":"2022010901430749000_b5","first-page":"241","article-title":"Fibronectin release by systemic sclerosis and normal dermal fibroblasts in response to TGF-beta","volume":"18","author":"Xu","year":"1991","journal-title":"J Rheumatol"},{"key":"2022010901430749000_b6","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s004030050241","article-title":"Gene expression of types I and III collagen, decorin, matrix metalloproteinases and tissue inhibitors of metalloproteinases in skin fibroblasts from patients with systemic sclerosis","volume":"289","author":"Kuroda","year":"1997","journal-title":"Arch Dermatol Res"},{"key":"2022010901430749000_b7","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1146\/annurev.cellbio.17.1.463","article-title":"How matrix metalloproteinases regulate cell behavior","volume":"17","author":"Sternlicht","year":"2001","journal-title":"Annu Rev Cell Dev Biol"},{"key":"2022010901430749000_b8","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1042\/bj1660021","article-title":"Further studies on the activation of procollagenase, the latent precursor of bone collagenase. Effects of lysosomal cathepsin B, plasmin and kallikrein, and spontaneous activation","volume":"166","author":"Eeckhout","year":"1977","journal-title":"Biochem J"},{"key":"2022010901430749000_b9","doi-asserted-by":"crossref","first-page":"14313","DOI":"10.1074\/jbc.270.24.14313","article-title":"The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and its inhibitory activities define the distinct TIMP gene family","volume":"270","author":"Apte","year":"1995","journal-title":"J Biol Chem"},{"key":"2022010901430749000_b10","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1046\/j.1523-1747.2003.12097.x","article-title":"Function blocking autoantibodies against matrix metalloproteinase-1 in patients with systemic sclerosis","volume":"120","author":"Sato","year":"2003","journal-title":"J Invest Dermatol"},{"key":"2022010901430749000_b11","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0889-857X(05)70297-0","article-title":"Antinuclear antibody in systemic sclerosis (scleroderma)","volume":"22","author":"Okano","year":"1996","journal-title":"Rheum Dis Clin North Am"},{"key":"2022010901430749000_b12","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1093\/rheumatology\/40.10.1135","article-title":"Clinical significance of anti-topoisomerase I antibody levels determined by ELISA in systemic sclerosis","volume":"40","author":"Sato","year":"2001","journal-title":"Rheumatology (Oxford)"},{"key":"2022010901430749000_b13","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1172\/JCI0215078","article-title":"CD19-dependent B lymphocyte signaling thresholds influence skin fibrosis and autoimmunity in the tight-skin mouse","volume":"109","author":"Saito","year":"2002","journal-title":"J Clin Invest"},{"key":"2022010901430749000_b14","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/art.1780230510","article-title":"Preliminary criteria for the classification of systemic sclerosis (scleroderma)","volume":"23","author":"Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee.","year":"1980","journal-title":"Arthritis Rheum"},{"key":"2022010901430749000_b15","first-page":"202","article-title":"Scleroderma (systemic sclerosis): classification, subsets and pathogenesis","volume":"15","author":"LeRoy","year":"1988","journal-title":"J Rheumatol"},{"key":"2022010901430749000_b16","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1002\/art.1780251101","article-title":"The 1982 revised criteria for the classification of systemic lupus erythematosus","volume":"25","author":"Tan","year":"1982","journal-title":"Arthritis Rheum"},{"key":"2022010901430749000_b17","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/art.1780350606","article-title":"Derivation of the SLEDAI: a disease activity index for lupus patients","volume":"35","author":"Bombardier","year":"1992","journal-title":"Arthritis Rheum"},{"key":"2022010901430749000_b18","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1056\/NEJM197502132920706","article-title":"Polymyositis and dermatomyositis (first of two parts)","volume":"292","author":"Bohan","year":"1975","journal-title":"N Engl J Med"},{"key":"2022010901430749000_b19","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJM197502202920807","article-title":"Polymyositis and dermatomyositis (second of two parts)","volume":"292","author":"Bohan","year":"1975","journal-title":"N Engl J Med"},{"key":"2022010901430749000_b20","first-page":"1892","article-title":"Skin thickness score in systemic sclerosis: an assessment of inter-observer variability in three independent studies","volume":"20","author":"Clements","year":"1993","journal-title":"J Rheumatol"},{"key":"2022010901430749000_b21","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1002\/art.1780310207","article-title":"Clinical correlations and prognosis based on serum autoantibodies in patients with systemic sclerosis","volume":"31","author":"Steen","year":"1988","journal-title":"Arthritis Rheum"},{"key":"2022010901430749000_b22","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1093\/rheumatology\/40.4.406","article-title":"Renal vascular damage in Japanese patients with systemic sclerosis","volume":"40","author":"Nishijima","year":"2001","journal-title":"Rheumatology (Oxford)"},{"key":"2022010901430749000_b23","doi-asserted-by":"crossref","first-page":"6635","DOI":"10.4049\/jimmunol.165.11.6635","article-title":"Quantitative genetic variation in CD19 expression correlates with autoimmunity","volume":"165","author":"Sato","year":"2000","journal-title":"J Immunol"},{"key":"2022010901430749000_b24","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S1525-1578(10)60652-6","article-title":"A novel method to compensate for different amplification efficiencies between patient DNA samples in quantitative real-time PCR","volume":"3","author":"Meijerink","year":"2001","journal-title":"J Mol Diagn"},{"key":"2022010901430749000_b25","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/1523-1747.ep12394936","article-title":"Decreased collagenase expression in cultured systemic sclerosis fibroblasts","volume":"103","author":"Takeda","year":"1994","journal-title":"J Invest Dermatol"},{"key":"2022010901430749000_b26","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0009-8981(94)90255-0","article-title":"Excess matrix accumulation in scleroderma is caused partly by differential regulation of stromelysin and TIMP-1 synthesis","volume":"231","author":"Bou-Gharios","year":"1994","journal-title":"Clin Chim Acta"},{"key":"2022010901430749000_b27","doi-asserted-by":"crossref","first-page":"3423","DOI":"10.1074\/jbc.270.7.3423","article-title":"Myofibroblasts from scleroderma skin synthesize elevated levels of collagen and tissue inhibitor of metalloproteinase (TIMP-1) with two forms of TIMP-1","volume":"270","author":"Kirk","year":"1995","journal-title":"J Biol Chem"},{"key":"2022010901430749000_b28","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/1523-1747.ep12286457","article-title":"Tissue inhibitor of metalloproteinase 1 (TIMP-1) may be an autocrine growth factor in scleroderma fibroblasts","volume":"108","author":"Kikuchi","year":"1997","journal-title":"J Invest Dermatol"},{"key":"2022010901430749000_b29","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/0190-9622(95)90289-9","article-title":"Serum tissue inhibitor of metalloproteinases in patients with systemic sclerosis","volume":"33","author":"Kikuchi","year":"1995","journal-title":"J Am Acad Dermatol"},{"key":"2022010901430749000_b30","first-page":"846","article-title":"Serum TIMP-1, TIMP-2, and MMP-1 in patients with systemic sclerosis, primary Raynaud's phenomenon, and in normal controls","volume":"60","author":"Young-Min","year":"2001","journal-title":"Ann Rheum Dis"},{"key":"2022010901430749000_b31","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1046\/j.1523-1747.1998.00138.x","article-title":"Activation of tissue inhibitor of metalloproteinases-3 (TIMP-3) mRNA expression in scleroderma skin fibroblasts","volume":"110","author":"Mattila","year":"1998","journal-title":"J Invest Dermatol"},{"key":"2022010901430749000_b32","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1161\/01.CIR.95.4.831","article-title":"Human connective tissue growth factor is expressed in advanced atherosclerotic lesions","volume":"95","author":"Oemar","year":"1997","journal-title":"Circulation"},{"key":"2022010901430749000_b33","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1002\/hep.510300425","article-title":"Expression of connective tissue growth factor in experimental rat and human liver fibrosis","volume":"30","author":"Paradis","year":"1999","journal-title":"Hepatology"},{"key":"2022010901430749000_b34","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1006\/jmcc.2000.1215","article-title":"CTGF expression is induced by TGF-beta in cardiac fibroblasts and cardiac myocytes: a potential role in heart fibrosis","volume":"32","author":"Chen","year":"2000","journal-title":"J Mol Cell Cardiol"},{"key":"2022010901430749000_b35","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1083\/jcb.114.6.1285","article-title":"Connective tissue growth factor: a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC induced immediate early gene product CEF-10","volume":"114","author":"Bradham","year":"1991","journal-title":"J Cell Biol"},{"key":"2022010901430749000_b36","doi-asserted-by":"crossref","first-page":"10594","DOI":"10.1074\/jbc.M010149200","article-title":"CTGF and SMADs, maintenance of scleroderma phenotype is independent of SMAD signaling","volume":"276","author":"Holmes","year":"2001","journal-title":"J Biol Chem"},{"key":"2022010901430749000_b37","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1006\/excr.2000.4972","article-title":"Autocrine overexpression of CTGF maintains fibrosis: RDA analysis of fibrosis genes in systemic sclerosis","volume":"259","author":"Shi-wen","year":"2000","journal-title":"Exp Cell Res"},{"key":"2022010901430749000_b38","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1091\/mbc.4.6.637","article-title":"Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair","volume":"4","author":"Igarashi","year":"1993","journal-title":"Mol Biol Cell"},{"key":"2022010901430749000_b39","first-page":"149","article-title":"Serum levels of connective tissue growth factor are elevated in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis","volume":"27","author":"Sato","year":"2000","journal-title":"J Rheumatol"},{"key":"2022010901430749000_b40","doi-asserted-by":"crossref","first-page":"36288","DOI":"10.1074\/jbc.M201674200","article-title":"Matrix metalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165","volume":"277","author":"Hashimoto","year":"2002","journal-title":"J Biol Chem"},{"key":"2022010901430749000_b41","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0049-0172(75)90017-7","article-title":"Pathogenesis of systemic sclerosis: a vascular hypothesis","volume":"4","author":"Campbell","year":"1975","journal-title":"Semin Arthritis Rheum"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2249.2004.02615.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/138\/2\/357\/42082232\/j.1365-2249.2004.02615.x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/138\/2\/357\/42082232\/j.1365-2249.2004.02615.x.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,9]],"date-time":"2022-01-09T01:47:56Z","timestamp":1641692876000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/138\/2\/357\/6439868"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,10,7]]},"references-count":41,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2004,10,20]]},"published-print":{"date-parts":[[2004,10,7]]}},"URL":"https:\/\/doi.org\/10.1111\/j.1365-2249.2004.02615.x","relation":{},"ISSN":["1365-2249","0009-9104"],"issn-type":[{"value":"1365-2249","type":"electronic"},{"value":"0009-9104","type":"print"}],"subject":[],"published-other":{"date-parts":[[2004,11]]},"published":{"date-parts":[[2004,10,7]]}}}