{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:51:38Z","timestamp":1790682698067,"version":"4.1.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2013,12,20]],"date-time":"2013-12-20T00:00:00Z","timestamp":1387497600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2013,12,20]],"date-time":"2013-12-20T00:00:00Z","timestamp":1387497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p><jats:italic>In vitro<\/jats:italic> apoptosis of peripheral monocytes in rheumatoid arthritis (RA) is disturbed and influenced by cytokine production and transmembrane TNF (tmTNF) reverse signaling. The goal of the study was the analysis of the predictive value of the rate of <jats:italic>in vitro<\/jats:italic> apoptosis for the therapeutic response to anti-TNF treatment.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Spontaneous and tmTNF reverse signaling-induced apoptosis were determined <jats:italic>in vitro<\/jats:italic> in monocytes from 20 RA patients prior to initiation of therapeutic TNF inhibition with etanercept, and the subsequent clinical response was monitored.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Spontaneous <jats:italic>in vitro<\/jats:italic> apoptosis was significantly reduced in RA patients compared to controls. Deficiency in spontaneous apoptosis was associated with an insufficient therapeutic response according to the European League Against Rheumatism (EULAR) response criteria and less reduction of the disease activity determined by disease activity score (DAS) 28. High susceptibility to reverse signaling-induced apoptosis was also associated with less efficient reduction in the DAS28. Of note, a strong negative correlation between the two apoptotic parameters was discernible, possibly indicative of two pathogenetically relevant processes counter-regulating each other.<\/jats:p>\n                        <jats:p>tmTNF reverse signaling induced <jats:italic>in vitro<\/jats:italic> production of soluble IL1-RI and IL-1RII only in monocytes not deficient in spontaneous apoptosis, and the levels of soluble IL1-RII were found to be predictive of a good clinical response to Etanercept.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>Although tmTNF reverse signaling is able to induce apoptosis of RA monocytes <jats:italic>in vitro<\/jats:italic>, this process appears to occur <jats:italic>in vitro<\/jats:italic> preferentially in patients with suboptimal therapeutic response. Resistance to spontaneous <jats:italic>in vitro<\/jats:italic> apoptosis, in contrast, is a predictor of insufficient response to treatment.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar4416","type":"journal-article","created":{"date-parts":[[2013,12,20]],"date-time":"2013-12-20T10:07:51Z","timestamp":1387534071000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Deficient spontaneous in vitro apoptosis and increased tmTNF reverse signaling-induced apoptosis of monocytes predict suboptimal therapeutic response of rheumatoid arthritis to TNF inhibition"],"prefix":"10.1186","volume":"15","author":[{"given":"Undine","family":"Meusch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Klingner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Baerwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Rossol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,12,20]]},"reference":[{"key":"4087_CR1","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1053\/j.gastro.2004.11.060","volume":"128","author":"H Mitoma","year":"2005","unstructured":"Mitoma H, Horiuchi T, Hatta N, Tsukamoto H, Harashima SI, Kikuchi Y, Otsuka J, Okamura S, Fujita S, Harada M: Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-alpha. 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