{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:25:11Z","timestamp":1788956711602,"version":"build-2803163510"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2005,1,26]],"date-time":"2005-01-26T00:00:00Z","timestamp":1106697600000},"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":[[2005,1,26]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Associations of Epstein\u2013Barr virus (EBV) and autoimmune diseases have been hypothesized. We have analysed IgG antibodies to EBV nuclear antigen (EBNA)-2 in sera from Japanese patients with autoimmune systemic connective tissue diseases (CTD), exemplified by systemic lupus erythematosus (SLE), primary Sj\u00f6gren's syndrome (SS), rheumatoid arthritis (RA), systemic sclerosis\u200a (SSc)\u200a and\u200a secondary\u200a SS\u200a (classical\u200a CTDs\u200a complicated\u200a with\u200a SS). An\u200a enzyme-linked\u200a immunosorbent\u200a assay\u200a (ELISA)\u200a which\u200a uses\u200a glutathione-S-transferase polypeptides fused to EBV nuclear antigen (EBNA)-2 and EBNA-1 was developed. Ratios of IgG antibody reactivity to whole IgG concentrations of sera were calculated to normalize EBNA-2 and EBNA-1 antibody levels to the hypergammaglobulinaemia that occurs in CTD. The ELISA optical density OD450 readings of IgG antibodies to both the amino-terminal aa 1\u2013116 of EBNA-2 and carboxyl-terminal aa 451\u2013641 of EBNA-1 were elevated significantly in patients with SLE, primary SS, RA, SSc and secondary SS when compared to EBNA-1. The OD readings were divided by serum IgG concentrations to normalize for the hypergammaglobulinaemia. The specific levels of IgG antibodies to the amino-terminal region of EBNA-2 were elevated in patients with SLE, primary SS or RA, as well as those with secondary SS complicated with SLE or RA. The EBNA-2 amino-terminal region contains a polyproline tract and a proline-rich sequence and has considerable amino acid sequence homology with many cellular proline-rich proteins. High ratios of EBNA-2 aa 1\u2013116 to EBNA-1 aa 451\u2013641 IgG antibody levels which probably suggest reactivation of EBV latent infection were associated significantly with pulmonary involvement in SS patients. These results are consistent with the hypothesis that the sequence similarity between the amino-terminal region of EBNA-2 and proline-rich cellular proteins is associated with pathogenesis in a subpopulation of CTD patients, possibly by the molecular mimicry\u2013epitope shift mechanism.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2004.02704.x","type":"journal-article","created":{"date-parts":[[2005,2,23]],"date-time":"2005-02-23T13:14:44Z","timestamp":1109164484000},"page":"558-568","source":"Crossref","is-referenced-by-count":27,"title":["Elevated immunoglobulin G antibodies to the proline-rich amino-terminal region of Epstein\u2013Barr virus nuclear antigen-2 in sera from patients with systemic connective tissue diseases and from a subgroup of Sj\u00f6gren's syndrome patients with pulmonary involvements"],"prefix":"10.1093","volume":"139","author":[{"given":"M","family":"Yamazaki","sequence":"first","affiliation":[{"name":"Herpesvirus Laboratory, Department of Virology I, National Institute of Infectious Diseases, Tokyo"},{"name":"Department of Viral Diagnostics, Denka Seiken, Minamihoncho, Gosen City, Niigata"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Herpesvirus Laboratory, Department of Virology I, National Institute of Infectious Diseases, Tokyo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Kusano","sequence":"additional","affiliation":[{"name":"Herpesvirus Laboratory, Department of Virology I, National Institute of Infectious Diseases, Tokyo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Eda","sequence":"additional","affiliation":[{"name":"Herpesvirus Laboratory, Department of Virology I, National Institute of Infectious Diseases, Tokyo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Viral Diagnostics, Denka Seiken, Minamihoncho, Gosen City, Niigata"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Okawa-Takatsuji","sequence":"additional","affiliation":[{"name":"Department of Community Health and Medicine, Research Institute, International Medical Center of Japan, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Aotsuka","sequence":"additional","affiliation":[{"name":"Department of Community Health and Medicine, Research Institute, International Medical Center of Japan, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Yanagi","sequence":"additional","affiliation":[{"name":"Herpesvirus Laboratory, Department of Virology I, National Institute of Infectious Diseases, 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