{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:08:57Z","timestamp":1777860537302,"version":"3.51.4"},"reference-count":11,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n \n Variants in\n RELA<\/jats:italic>\n (which encodes the p65 subunit of NF-\u03baB) can cause a monogenic autoinflammatory disease with clinical manifestations that range from mucocutaneous lesions (Beh\u00e7et\u2019s disease-like) to systemic inflammation. However, the diversity of the phenotype and its penetrance are uncertain.\n <\/jats:p>\n <\/jats:sec>\n \n Case presentation<\/jats:title>\n \n Patient 1 (p.Asp465Thrfs14) presented with classic Beh\u00e7et\u2019s disease-like symptoms of oral and genital ulcers, fever, and elevated inflammatory markers. Colchicine (0.25 mg once daily) with low-dose glucocorticoids led to remission. Exploratory\n in vitro<\/jats:italic>\n assays using murine fibroblasts indicated increased TNF-\u03b1\u2013induced apoptosis associated with the\n RELA<\/jats:italic>\n variant. Patient 2 (p.Glu495Serfs6) had no mucosal lesions but experienced recurrent high fever, hyperferritinemia, uveitis\/scleritis, and progressive bilateral sensorineural hearing loss. Because IL-1 blockers were not available, we administered adalimumab as a steroid-sparing treatment. Defervescence was achieved within 6 months of adalimumab therapy, with stabilization of inflammatory markers and hearing thresholds during the entire 9-month follow-up. PBMCs from Patient 2 and the carrier mother that were stimulated by LPS had decreased induction of two genes targeted by NF-\u03baB (\n BCL2A1<\/jats:italic>\n ,\n TRAF1<\/jats:italic>\n ), and the proband (but not the mother) had markedly increased IL-6 secretion.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n C-terminal truncations in the transcriptional activation domain of\n RELA<\/jats:italic>\n lead to haploinsufficiency and an inflammatory phenotype that depends on the cell type and stimulus.\n RELA<\/jats:italic>\n screening should be considered in the evaluation of children with unexplained autoinflammatory presentation, even in the absence of mucosal ulceration.\n <\/jats:p>\n 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