{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:08:31Z","timestamp":1791349711037,"version":"4.3.1"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,4,25]],"date-time":"2008-04-25T00:00:00Z","timestamp":1209081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Three anti\u2013tumor necrosis factor \u03b1 (anti\u2010TNF\u03b1) agents have been proved to be effective for rheumatoid arthritis (RA) and other inflammatory disorders. Infliximab and adalimumab have been generated as anti\u2010TNF\u03b1 monoclonal antibodies, while etanercept is engineered from human type II TNF receptors. In spite of all 3 agents' equal efficacy for RA, both infliximab and adalimumab are effective for other diseases such as Crohn's disease and Wegener's granulomatosis, while etanercept is not. We undertook this study to understand the different clinical effects of these anti\u2010TNF\u03b1 agents by analyzing their biologic activities on transmembrane TNF\u03b1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Jurkat T cells stably expressing an uncleavable form of transmembrane TNF\u03b1 were used for the following studies: 1) flow cytometric analysis of binding activities of anti\u2010TNF agents to cell surface transmembrane TNF\u03b1, 2) complement\u2010dependent cytotoxicity (CDC), 3) antibody\u2010dependent cell\u2010mediated cytotoxicity (ADCC) by using peripheral blood mononuclear cells, and 4) outside\u2010to\u2010inside (reverse) signal transduction through transmembrane TNF\u03b1 estimated by apoptosis and cell cycle analysis using flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All of the anti\u2010TNF\u03b1 agents bound to transmembrane TNF\u03b1. Infliximab and adalimumab exerted almost equal CDC activities, while etanercept showed considerably lower activity. ADCC activities were almost equal among these 3 agents. Adalimumab and infliximab induced apoptosis and cell cycle arrest in transmembrane TNF\u03b1\u2013expressing Jurkat T cells, reflecting an outside\u2010to\u2010inside signal transduction through transmembrane TNF\u03b1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Three different anti\u2010TNF agents showed different biologic effects on transmembrane TNF\u03b1. This finding suggests that CDC and outside\u2010to\u2010inside signals by anti\u2010TNF\u03b1 antibodies may explain the successful clinical efficacy of adalimumab and infliximab in Crohn's disease and Wegener's granulomatosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.23447","type":"journal-article","created":{"date-parts":[[2008,4,25]],"date-time":"2008-04-25T16:47:41Z","timestamp":1209142061000},"page":"1248-1257","source":"Crossref","is-referenced-by-count":305,"title":["Mechanisms for cytotoxic effects of anti\u2013tumor necrosis factor agents on transmembrane tumor necrosis factor \u03b1\u2013expressing cells: Comparison among infliximab, etanercept, and adalimumab"],"prefix":"10.1002","volume":"58","author":[{"given":"Hiroki","family":"Mitoma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiko","family":"Horiuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Tsukamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Tamimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutaka","family":"Kimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Uchino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"To","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin\u2010Ichi","family":"Harashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuaki","family":"Hatta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mine","family":"Harada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,4,25]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.163"},{"key":"e_1_2_6_3_2","doi-asserted-by":"crossref","first-page":"957","DOI":"10.4049\/jimmunol.138.3.957","article-title":"Cell\u2010associated 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