{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T14:06:30Z","timestamp":1767967590235,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2013,10,16]],"date-time":"2013-10-16T00:00:00Z","timestamp":1381881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To analyze proliferation and pro\u2010inflammatory cytokine production of peripheral blood mononuclear cells (<jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>) from rheumatoid arthritis (<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>) patients following stimulation with a purified chondrocyte membrane\u2010associated autoantigen (<jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content>65).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content>65 was highly purified from bovine chondrocyte membranes by solubilization and ion exchange chromatography. <jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content> of <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> patients (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>37; 28 seropositive, nine seronegative) and non\u2010arthritic donors (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>20) were isolated by ficoll centrifugation and used in cell proliferation assays. The levels of interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u20101, tumo necrosis factor (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 produced after stimulation with <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content>65 were determined by enzyme\u2010linked immunosorbent assay (<jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>). Statistical analysis was performed using <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>ann\u2013<jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>hitney <jats:italic>U<\/jats:italic>\u2010test and <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>pearman rank test and the software <jats:styled-content style=\"fixed-case\">SPSS<\/jats:styled-content> 13.0<jats:sup>TM<\/jats:sup> (SPSS Inc.; Chicago, IL, USA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Peripheral blood mononuclear cells exhibited a strong proliferative response to purified <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content>65 in approximately 50% of the <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> patients (seropositive\u00a0&gt;\u00a0seronegative), with a maximum reactivity at 0.15 or 0.30\u00a0\u03bcg\/mL culture medium. In contrast, <jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content> from normal donors did not show a proliferative response to <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content>65 at any dose. The proliferative response in <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> patients peaked at days 7\u20139 and returned to control levels at day 13, indicating an antigen\u2010driven process. <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content>65\u2010stimulated <jats:styled-content style=\"fixed-case\">RA PBMC<\/jats:styled-content> produced moderate to high amounts of IL\u20101, TNF and IL\u20106. This was comparable to the response after exposure to isolated whole chondrocyte membranes or purified collagen type II.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results demonstrate a significant cellular immune response to <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content>65 protein in <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> patients. Given the high similarity between bovine and human <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content>65, the results suggest a pathogenetic involvement of this molecule as a cartilage\u2010specific potential target autoantigen in <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.12167","type":"journal-article","created":{"date-parts":[[2013,10,16]],"date-time":"2013-10-16T14:02:56Z","timestamp":1381932176000},"page":"1132-1141","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Induction of proliferation and pro\u2010inflammatory cytokine production in rheumatoid arthritis peripheral blood mononuclear cells by a 65\u00a0KDa chondrocyte membrane\u2010specific, constitutive target autoantigen (<scp>CH<\/scp>65)"],"prefix":"10.1111","volume":"20","author":[{"given":"Rayya 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