{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T19:26:20Z","timestamp":1770146780769,"version":"3.49.0"},"reference-count":48,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2002,11,8]],"date-time":"2002-11-08T00:00:00Z","timestamp":1036713600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2002,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To analyze the reaction of lupus sera with proliferating cell nuclear antigen (PCNA) multiprotein complexes (PCNA complexes), which are part of the protein machinery involved in cell proliferation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PCNA complexes were purified from rabbit thymus extract by affinity chromatography using anti\u2010PCNA monoclonal antibodies (TOB7, TO17, and TO30); monomeric and trimeric PCNA forms (AK\u2010PCNA) were purified using anti\u2010PCNA serum AK. The reactions to these antigens of 10 anti\u2010PCNA\u2013positive and 40 anti\u2010PCNA\u2013negative sera selected from 560 lupus patients were tested by immunoblotting, immunoprecipitation, and enzyme\u2010linked immunosorbent assays (ELISAs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>With one exception (serum OK), anti\u2010PCNA\u2013positive sera reacted exclusively with only the 34\u2010kd polypeptide. In contrast, 14 of 40 anti\u2010PCNA\u2013negative sera reacted with multiple proteins within PCNA complexes. Most anti\u2010PCNA\u2013positive sera probably recognize as epitopes the binding sites for other proteins on PCNA, which are likely hidden when PCNA is complexed with other proteins. As a consequence, only serum OK reacted with the PCNA complex in a series of ELISAs. Using AK\u2010PCNA as a competitive inhibitor, it was determined that serum OK reacts with both the 58\u2010kd polypeptide and the 34\u2010kd PCNA within complexes. Together with the results of a longitudinal analysis, these results suggest that the immune system of patient OK likely recognized the complexed PCNA protein, after which the autoimmune response spread to other elements of the complexes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Intermolecular\u2013intrastructural help, leading to the spread of autoimmune response from PCNA to other proteins associated with its biologic function, plays a crucial role in the induction of the autoimmune response seen in lupus patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.10606","type":"journal-article","created":{"date-parts":[[2002,11,12]],"date-time":"2002-11-12T18:42:32Z","timestamp":1037126552000},"page":"2946-2956","source":"Crossref","is-referenced-by-count":13,"title":["Autoimmune responses to proliferating cell nuclear antigen multiprotein complexes involved in cell proliferation are strongly associated with their structure and biologic function in patients 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