{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:00:27Z","timestamp":1785222027191,"version":"3.55.0"},"reference-count":27,"publisher":"Baishideng Publishing Group Inc.","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Clin Pediatr"],"abstract":"BACKGROUND<\/jats:p>\n The TNFRSF1A gene encodes TNFR1, which regulates inflammation and apoptosis. Variants in this gene present with an autoinflammatory phenotype and are linked to tumor necrosis factor receptor associated periodic syndrome (TRAPS), an orphan monogenic autoinflammatory disease (AID) that can mimic systemic juvenile idiopathic arthritis (sJIA) and other rheumatic diseases. Despite known mechanisms and classification criteria, diagnosing and choosing therapy for patients with TNFRSF1A variants remains challenging. Assessing phenotypic characteristics and considering alternative therapies for these patients is important.<\/jats:p>\n AIM<\/jats:p>\n To evaluate the clinical and laboratory features of sJIA associated with the TNFRSF1A gene and treatment outcomes.<\/jats:p>\n METHODS<\/jats:p>\n A single-center, retrospective, cross-sectional cohort study with longitudinal follow-up was performed. A total of 66 patients with fever and a referral diagnosis of sJIA were included: 33 (50%) had TNFRSF1A gene variants identified by molecular genetic testing, and 33 (50%) had no TNFRSF1A or other autoinflammatory gene variants. Demographic, clinical, laboratory, and treatment data were collected before and after verification of AID, and again at 3, 6, and 12 months.<\/jats:p>\n RESULTS<\/jats:p>\n Molecular genetic testing identified several TNFRSF1A variants. Of 33 patients, 4 (12%) had likely pathogenic variants, 1 (3%) had a pathogenic variant, and 3 (9.1%) had variants of uncertain significance; all were heterozygous. The most common, identified in 27 (82%), was a variant of uncertain significance (c.362G>A, p.Arg121Gln) with incomplete penetrance. These patients had paroxysmal (48.5%) or continuous fever (48.5%), rash (66.7%), joint syndrome (78.8%), abdominal pain (33.3%), gastrointestinal symptoms (27.2%), eye involvement (24.2%), chest pain (12.1%), hearing loss (9.1%), periorbital edema (9.1%), arrested development (6.1%), aseptic meningitis (3%), hydrocephalus (3%), and amyloidosis (3%). Endoscopic signs of intestinal damage were found in 20 patients (60.6%): 11 showed upper gastrointestinal tract issues; 9 had intestinal pathology. All patients with TNFRSF1A variants received antirheumatic therapy before genetic testing. Treatments included intravenous glucocorticoids (GC) (45.5%), oral GC (45.5%), intravenous immunoglobulin (18.1%), methotrexate (48.5%), cyclosporine (18.1%), azathioprine (3%), mesalazine (3%), sulfasalazine (3%), and biological (b) disease-modifying antirheumatic drugs (bDMARDs) (72.7%). Of those on bDMARDs, 39.4% received tocilizumab, 9.1% abatacept, 6.1% canakinumab, 6.1% infliximab, 3% rituximab, 3% etanercept, 3% adalimumab, and 3% certolizumab pegol. Among 24 patients with three prior bDMARD switches before genetic diagnosis, 17 (70.8%) achieved remission: 7 on tocilizumab, 6 on canakinumab, 2 on adalimumab, 1 on infliximab, and 1 on rituximab. After confirming AID, all patients received biological therapy: 9 previously untreated patients started canakinumab (3), tocilizumab (3), or etanercept (3); 7 switched drugs after ineffective prior therapy. After all therapy adjustments, all patients achieved remission: 13 on tocilizumab, 11 on canakinumab, 3 on adalimumab, 2 on etanercept, 1 on golimumab, 1 on rituximab, and 1 with GC and colchicine followed by withdrawal. Patients started on bDMARDs after genetic testing required fewer drug switches than those treated empirically before diagnosis (0.23 \u00b1 0.42 vs 0.9 \u00b1 0.6, P = 0.001).<\/jats:p>\n CONCLUSION<\/jats:p>\n Variants in the TNFRSF1A gene may cause a wide range of clinical symptoms, including eye and intestinal lesions that are not typical of sJIA. All patients with fever and unusual sJIA symptoms should have molecular genetic testing for TNFRSF1A variants to confirm or exclude AID early. Early diagnosis enables timely therapy and prevents complications. Tocilizumab (39.3%), canakinumab (33.3%), and TNF inhibitors (21.2%) achieved remission in children with TNFRSF1A variants. Some patients required multiple bDMARD switches to achieve remission, highlighting the complexity of treatment decisions in this group.<\/jats:p>","DOI":"10.5409\/wjcp.119428","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T06:28:22Z","timestamp":1785220102000},"source":"Crossref","is-referenced-by-count":0,"title":["Clinical and laboratory manifestations and treatment of children with\n TNFRSF1A<\/i>\n gene variants"],"prefix":"10.5409","volume":"15","author":[{"given":"Ekaterina I","family":"Alexeeva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiri Sh","family":"Shingarova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana M","family":"Dvoryakovskaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ksenia B","family":"Isaeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra M","family":"Chomakhidze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna N","family":"Fetisova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina V","family":"Chibisova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizaveta A","family":"Krekhova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan A","family":"Kriulin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana Y","family":"Kriulina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina T","family":"Tsulukiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria S","family":"Botova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya M","family":"Kondratyeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Y","family":"Kokina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia A","family":"Makunc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narvik A","family":"Dostiev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirill V","family":"Savostyanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandr A","family":"Pushkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya S","family":"Zhanin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry S","family":"Demyanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail M","family":"Kostik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2060","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.2023-1209"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.revmed.2018.02.002"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204184"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/art.21964"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-014-1150-5"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21093263"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.2332\/allergolint.55.337"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8562485"},{"key":"B9","unstructured":"Horneff G, Rhouma A, Weber C, Lohse P. 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