{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T04:31:59Z","timestamp":1766377919403},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2005,9,2]],"date-time":"2005-09-02T00:00:00Z","timestamp":1125619200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2005,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the molecular consequences of expressing mutated forms of tumor necrosis factor receptor I (TNFRI) as found in patients with TNFR\u2010associated periodic syndrome (TRAPS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We cloned and expressed full\u2010length wild\u2010type (WT) and T50K and P46L variants of TNFRI using a new tightly regulated doxycycline\u2010dependent expression system. This system enabled the study of molecular interactions between these receptors at both physiologic and pathophysiologic levels of expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We used chemical crosslinking on the cell surface to show that WT and mutant forms of TNFRI, derived from TRAPS patients, interact in the absence of TNF ligand. Doxycycline\u2010controlled up\u2010regulation of one TNFRI allele, either WT or mutant, caused down\u2010regulation of the other allele, indicating dynamic control of cell surface assembly. We also demonstrated that increased expression of mutant TNFRI (T50K) was associated with a parallel increase in NF\u2010\u03baB p65 (RelA) subunit activation, which did not occur with increased expression of WT TNFRI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The T50K TRAPS\u2010related variant is capable of sustaining inappropriate NF\u2010\u03baB activation, resulting in persistent autoinflammation in target organs such as skin, synovial membrane, and the central nervous system. We conclude that some of the inflammatory processes seen in TRAPS do not involve direct interaction of TNF with its receptors, but that other proinflammatory mechanisms capable of up\u2010regulating TNFRI expression may cause cellular activation through the NF\u2010\u03baB signaling pathway.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.21268","type":"journal-article","created":{"date-parts":[[2005,9,2]],"date-time":"2005-09-02T16:18:38Z","timestamp":1125677918000},"page":"2906-2916","source":"Crossref","is-referenced-by-count":59,"title":["Tumor necrosis factor receptor I from patients with tumor necrosis factor receptor\u2013associated periodic syndrome interacts with wild\u2010type tumor necrosis factor receptor I and induces ligand\u2010independent NF\u2010\u03baB activation"],"prefix":"10.1002","volume":"52","author":[{"given":"Nasim","family":"Yousaf","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Gould","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebun","family":"Aganna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Hammond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita M.","family":"Mirakian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark D.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham A.","family":"Hitman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael F.","family":"McDermott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuti","family":"Chernajovsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,9,2]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10429"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-200209000-00002"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/321976"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11169"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10224"},{"key":"e_1_2_6_7_2","first-page":"2519","article-title":"Two familial cases with tumor necrosis factor receptor\u2010associated periodic syndrome caused by a non\u2010cysteine mutation (T50M) in the TNFRSF1A gene associated with severe multiorganic 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