{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:33:46Z","timestamp":1790472826129,"version":"4.1.0"},"reference-count":26,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MSD-AVENIR"},{"name":"Region Occitanie prematuration program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>(1) Background: TNF inhibitors (TNFis) have revolutionized the treatment of rheumatoid arthritis (RA). However, 30\u201340% of RA patients do not respond adequately to those biologics. In addition to neutralizing soluble TNF, TNFis have the ability to bind the transmembrane form of TNF, tmTNF. Importantly, tmTNF can act itself as a receptor that induces \u201cReverse Signaling\u201d (RS) in cells. We previously showed that certolizumab, a Fab\u2019 TNFi, activates RS in human primary monocytes, at least in part through the transcription factor Nrf2 that is known to regulate the expression of genes involved in anti-inflammatory response and oxidative stress. (2) Methods: Here, we have developed an assay for the prediction of clinical response of RA patients to TNF inhibitors. This assay is based on mRNA quantitation of CD36 activation and of six genes induced by Nrf2 following tmTNF RS in fresh monocytes. (3) Results: We could predict the response to anti-TNF monoclonal antibodies (mAbs) with 93.3% accuracy. However, our method was not suitable for the prediction of the response to TNF soluble receptor etanercept. (4) Conclusions: We have developed a rather simple, short-term test that can be standardized. Predicting the response to TNF mAbs will help physicians offer the best available treatment and provide patients with personalized medicine.<\/jats:p>","DOI":"10.3390\/diagnostics15101232","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T08:44:58Z","timestamp":1747212298000},"page":"1232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Predicting Clinical Response to Monoclonal TNF Inhibitors in Rheumatoid Arthritis: A Transcriptomic Approach Based on Transmembrane TNF Reverse Signaling and Nrf2 Activation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5488-7333","authenticated-orcid":false,"given":"Katy","family":"Diallo","sequence":"first","affiliation":[{"name":"Institut Toulousain des Maladies Infectieuses et Inflammatoires (INFINITY), INSERM UMR1291, 31024 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Degbo\u00e9","sequence":"additional","affiliation":[{"name":"Institut Toulousain des Maladies Infectieuses et Inflammatoires (INFINITY), INSERM UMR1291, 31024 Toulouse, France"},{"name":"Faculty of Health, CHU Toulouse, University of Toulouse, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Baron","sequence":"additional","affiliation":[{"name":"Institut Toulousain des Maladies Infectieuses et Inflammatoires (INFINITY), INSERM UMR1291, 31024 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00efs","family":"Bellin-Robert","sequence":"additional","affiliation":[{"name":"Institut Toulousain des Maladies Infectieuses et Inflammatoires (INFINITY), INSERM UMR1291, 31024 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fr\u00e9d\u00e9ric","family":"Boyer","sequence":"additional","affiliation":[{"name":"Faculty of Health, CHU Toulouse, University of Toulouse, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Ruyssen-Witrand","sequence":"additional","affiliation":[{"name":"Faculty of Health, CHU Toulouse, University of Toulouse, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Constantin","sequence":"additional","affiliation":[{"name":"Institut Toulousain des Maladies Infectieuses et Inflammatoires (INFINITY), INSERM UMR1291, 31024 Toulouse, France"},{"name":"Faculty of Health, CHU Toulouse, University of Toulouse, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Rauwel","sequence":"additional","affiliation":[{"name":"Institut Toulousain des Maladies Infectieuses et Inflammatoires (INFINITY), INSERM UMR1291, 31024 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8890-9099","authenticated-orcid":false,"given":"Alain","family":"Cantagrel","sequence":"additional","affiliation":[{"name":"Faculty of Health, CHU Toulouse, University of Toulouse, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Luc","family":"Davignon","sequence":"additional","affiliation":[{"name":"Faculty of Health, CHU Toulouse, University of Toulouse, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1056\/NEJMra1909094","article-title":"Reframing Immune-Mediated Inflammatory Diseases through Signature Cytokine Hubs","volume":"385","author":"Schett","year":"2021","journal-title":"N. 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