{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:35:03Z","timestamp":1791164103245,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2006,11,24]],"date-time":"2006-11-24T00:00:00Z","timestamp":1164326400000},"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":[[2006,11,27]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Sj\u00f6gren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration, destruction of the salivary and lacrimal glands and production of autoantibodies against a variety of cellular proteins. The aberrant immune response against these autoantigens may begin or extend to other proteins that are not yet defined. Several studies have shown that autoantibody production is taking place in the affected salivary glands. In the present study, using proteomic approaches, we aimed to: (a) identify new autoantigens in the salivary glands of primary SS (pSS) patients and (b) evaluate the epigenetic changes of known autoantigens. Total parotid gland extracts of pSS patients were analysed using two-dimensional gel electrophoresis, sodium dodecyl sulphate\u2013polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot with pSS patients' sera or purified autoantibodies and immunoprecipitation using homologous IgG. Identification of the unknown proteins was performed using mass spectrometry (MS). Immunoblot analysis on two-dimensional gels using purified anti-La\/SSB antibodies revealed that pSS salivary glands contain high levels of post-translationally modified La\/SSB autoantigen, while the native form of the protein is recognized faintly, in contrast to normal controls. Moreover, salivary glands of pSS patients contain post-translationally modified actin that becomes immunogenic in the microenviroment of the affected tissue. The alteration of the physicochemical properties of self-proteins could thus contribute to the break of immune tolerance against them.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2006.03262.x","type":"journal-article","created":{"date-parts":[[2006,11,24]],"date-time":"2006-11-24T09:13:29Z","timestamp":1164359609000},"page":"81-89","source":"Crossref","is-referenced-by-count":21,"title":["Analysis of parotid glands of primary Sj\u00f6gren's syndrome patients using proteomic technology reveals altered autoantigen composition and novel antigenic targets"],"prefix":"10.1093","volume":"147","author":[{"given":"E A","family":"Stea","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, Medical School, University of Athens"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J G","family":"Routsias","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Medical School, University of Athens"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Samiotaki","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Research Center \u2018Alexander Fleming"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Panayotou","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Research Center \u2018Alexander Fleming"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Papalambros","sequence":"additional","affiliation":[{"name":"1st Surgical Department, University of Athens, \u2018LAIKO\u2019 Hospital, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H M","family":"Moutsopoulos","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Medical School, University of Athens"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A G","family":"Tzioufas","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Medical School, University of Athens"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,11,24]]},"reference":[{"key":"2022010415141673600_b1","first-page":"1431","article-title":"Sj\u00f6gren's syndrome","volume-title":"Rheumatology","author":"Tzioufas","year":"2003"},{"key":"2022010415141673600_b2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/10408360500523837","article-title":"Autoantibodies to intracellular autoantigens and their B-cell epitopes: molecular probes to study the autoimmune response","volume":"43","author":"Routsias","year":"2006","journal-title":"Crit Rev Clin Lab Sci"},{"key":"2022010415141673600_b3","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/0896-8411(89)90189-3","article-title":"Autoantibody synthesis in salivary glands of Sj\u00f6gren's syndrome patients","volume":"2","author":"Horsfall","year":"1989","journal-title":"J 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damage","volume":"15","author":"Rosen","year":"2004","journal-title":"Crit Rev Oral Biol Med"},{"key":"2022010415141673600_b7","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1084\/jem.185.5.843","article-title":"Proteins phosphorylated during stress-induced apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus","volume":"185","author":"Utz","year":"1997","journal-title":"J Exp Med"},{"key":"2022010415141673600_b8","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1046\/j.1365-2249.2003.02246.x","article-title":"Calreticulin binds preferentially with B cell linear epitopes of Ro60 kD autoantigen, enhancing recognition by anti-Ro60 kD autoantibodies","volume":"134","author":"Staikou","year":"2003","journal-title":"Clin Exp Immunol"},{"key":"2022010415141673600_b9","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1084\/jem.179.4.1317","article-title":"Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes","volume":"179","author":"Casciola-Rosen","year":"1994","journal-title":"J Exp Med"},{"key":"2022010415141673600_b10","first-page":"6160","article-title":"Expression of epidermal growth factor and transforming growth factor-beta in human salivary gland adenocarcinoma cell line","volume":"45","author":"Sato","year":"1985","journal-title":"Cancer Res"},{"key":"2022010415141673600_b11","doi-asserted-by":"crossref","first-page":"10766","DOI":"10.1016\/S0021-9258(18)33889-4","article-title":"A one-step purification of membrane proteins using a high efficiency immunomatrix","volume":"257","author":"Schneider","year":"1982","journal-title":"J Biol Chem"},{"key":"2022010415141673600_b12","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/BF03402155","article-title":"Unmasking the anti-La\/SSB response in sera from patients with Sjogren's syndrome by specific blocking of anti-idiotypic antibodies to 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