{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T10:54:46Z","timestamp":1794480886618,"version":"4.9.1"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003356","name":"Gazi University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003356","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Clin Immunol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Beh\u00e7et\u2019s disease (BD) is a chronic inflammatory disorder characterized by recurrent oral aphthous ulcers, genital ulcers, skin lesions, and uveitis. Recent genetic studies have identified monogenic diseases with phenotypes resembling BD, including RELA\n                    <jats:italic>-<\/jats:italic>\n                    associated inflammatory disease (RAID),\n                    <jats:italic>Haploinsufficiency of A20<\/jats:italic>\n                    (HA20), and otulipenia. The\n                    <jats:italic>RelA<\/jats:italic>\n                    gene encodes the RELA protein, which is involved in the nuclear factor kappa B (NF-\u03baB) signaling pathway that regulates the transcription of genes associated with cell survival, apoptosis, and immune responses. In RAID, dysfunction of the NF-\u03baB pathway leads to reduced cell survival and symptoms of BD, such as recurrent fever, chronic mucocutaneous ulceration, arthralgia, and colitis. Herein, we report a pediatric patient who presented with recurrent, severe oral and genital ulcers from the age of five years and was diagnosed with RAID following a documented\n                    <jats:italic>RelA<\/jats:italic>\n                    gene mutation. The patient responded to a combination of corticosteroids, colchicine and methotrexate. RAID should be considered in the differential diagnosis of patients with early onset recurrent fever and mucosal ulcerations.\n                  <\/jats:p>","DOI":"10.1007\/s10875-025-01968-x","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T04:56:06Z","timestamp":1769489766000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Case-Based Literature Review of RELA Associated Inflammatory Diseases"],"prefix":"10.1007","volume":"46","author":[{"given":"Nihal","family":"Kara\u00e7ay\u0131r","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merve","family":"Yazol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emine Nur Sunar","family":"Yayla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pelin Esmeray","family":"\u015eenol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c7isem","family":"Y\u0131ld\u0131z","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuran","family":"Belder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merve","family":"Kutlar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Batuhan","family":"K\u00fc\u00e7\u00fckali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00fc\u015fra","family":"Acun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz Gezgin","family":"Y\u0131ld\u0131r\u0131m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevcan A.","family":"Bakkalo\u011flu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"1968_CR1","unstructured":"Ozen S. Beh\u00e7et disease. In: In: Petty RE, Laxer R, Lindsley C, Wedderburn L, Mellins ED, Fuhlbrigge RC, editors Textbook of Pediatric Rheumatology. 2020; 8th ed. Philadelphia, pp. 209\u2009\u2013\u200915."},{"issue":"5","key":"1968_CR2","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12973","volume":"92","author":"SF Perazzio","year":"2020","unstructured":"Perazzio SF, Allenspach EJ, Eklund KK, et al. Beh\u00e7et disease (BD) and BD-like clinical phenotypes: NF-\u03baB pathway in mucosal ulcerating diseases. Scand J Immunol. 2020;92(5):e12973. https:\/\/doi.org\/10.1111\/sji.12973.","journal-title":"Scand J Immunol"},{"issue":"25","key":"1968_CR3","doi-asserted-by":"publisher","first-page":"14405","DOI":"10.1073\/pnas.2002051117","volume":"117","author":"K Manthiram","year":"2020","unstructured":"Manthiram K, Preite S, Dedeoglu F, et al. Common genetic susceptibility loci link PFAPA syndrome, Beh\u00e7et\u2019s disease, and recurrent aphthous stomatitis. Proc Natl Acad Sci U S A. 2020;117(25):14405\u201311. https:\/\/doi.org\/10.1073\/pnas.2002051117.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1968_CR4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00399","author":"I Aksentijevich","year":"2017","unstructured":"Aksentijevich I, Zhou Q. NF-\u03baB pathway in autoinflammatory diseases: dysregulation of protein modifications by ubiquitin defines a new category of autoinflammatory diseases. Front Immunol. 2017. https:\/\/doi.org\/10.3389\/fimmu.2017.00399. 8:399. Published 2017 Apr 19.","journal-title":"Front Immunol"},{"key":"1968_CR5","doi-asserted-by":"publisher","DOI":"10.1111\/febs.17116","author":"LM Merlo Pich","year":"2024","unstructured":"Merlo Pich LM, Ziogas A, Netea MG. Genetic and epigenetic dysregulation of innate immune mechanisms in autoinflammatory diseases. FEBS J. 2024. https:\/\/doi.org\/10.1111\/febs.17116.","journal-title":"FEBS J"},{"key":"1968_CR6","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2024.1448176","volume":"12","author":"B Meertens","year":"2024","unstructured":"Meertens B, Hoste L, Tavernier SJ, Haerynck F. The riddle of recurrent fever: a clinical approach to pediatric autoinflammatory diseases. Front Pediatr. 2024;12:1448176. https:\/\/doi.org\/10.3389\/fped.2024.1448176.","journal-title":"Front Pediatr"},{"issue":"1","key":"1968_CR7","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1093\/rheumatology\/keac227","volume":"62","author":"K Lecerf","year":"2022","unstructured":"Lecerf K, Koboldt DC, Kuehn HS, et al. Case report and review of the literature: immune dysregulation in a large familial cohort due to a novel pathogenic RELA variant. Rheumatology (Oxford). 2022;62(1):347\u201359. https:\/\/doi.org\/10.1093\/rheumatology\/keac227.","journal-title":"Rheumatology (Oxford)"},{"issue":"1","key":"1968_CR8","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/ng.3459","volume":"48","author":"Q Zhou","year":"2016","unstructured":"Zhou Q, Wang H, Schwartz DM, et al. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease. Nat Genet. 2016;48(1):67\u201373. https:\/\/doi.org\/10.1038\/ng.3459.","journal-title":"Nat Genet"},{"issue":"7","key":"1968_CR9","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.1084\/jem.20160724","volume":"214","author":"YR Badran","year":"2017","unstructured":"Badran YR, Dedeoglu F, Leyva Castillo JM, et al. Human RELA haploinsufficiency results in autosomal-dominant chronic mucocutaneous ulceration. J Exp Med. 2017;214(7):1937\u201347. https:\/\/doi.org\/10.1084\/jem.20160724.","journal-title":"J Exp Med"},{"issue":"3","key":"1968_CR10","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1002\/art.41531","volume":"73","author":"F Adeeb","year":"2021","unstructured":"Adeeb F, Dorris ER, Morgan NE, et al. A novel RELA truncating mutation in a familial Beh\u00e7et\u2019s disease-like mucocutaneous ulcerative condition. Arthritis Rheumatol. 2021;73(3):490\u20137. https:\/\/doi.org\/10.1002\/art.41531.","journal-title":"Arthritis Rheumatol"},{"issue":"2","key":"1968_CR11","doi-asserted-by":"publisher","DOI":"10.3390\/children8020075","volume":"8","author":"M Shiraki","year":"2021","unstructured":"Shiraki M, Kadowaki S, Kadowaki T, Kawamoto N, Ohnishi H. Primary immunodeficiency disease mimicking pediatric Bechet\u2019s disease. Children. 2021;8(2):75. https:\/\/doi.org\/10.3390\/children8020075.","journal-title":"Children"},{"issue":"5","key":"1968_CR12","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30.","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405\u201324. https:\/\/doi.org\/10.1038\/gim.2015.30.","journal-title":"Genet Med"},{"issue":"1","key":"1968_CR13","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1002\/jbmr.2590","volume":"31","author":"AL Frederiksen","year":"2016","unstructured":"Frederiksen AL, Larsen MJ, Brusgaard K, et al. Neonatal high bone mass with first mutation of the NF-\u03baB complex: heterozygous de novo missense (p.Asp512Ser) RELA (Rela\/p65). J Bone Miner Res. 2016;31(1):163\u201372. https:\/\/doi.org\/10.1002\/jbmr.2590.","journal-title":"J Bone Miner Res"},{"issue":"4","key":"1968_CR14","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1016\/j.jaci.2017.11.036","volume":"141","author":"WA Comrie","year":"2018","unstructured":"Comrie WA, Faruqi AJ, Price S, et al. RELA haploinsufficiency in CD4 lymphoproliferative disease with autoimmune cytopenias. J Allergy Clin Immunol. 2018;141(4):1507-1510.e8. https:\/\/doi.org\/10.1016\/j.jaci.2017.11.036.","journal-title":"J Allergy Clin Immunol"},{"key":"1968_CR15","doi-asserted-by":"publisher","unstructured":"Barnebei L, Lamrini H, Castela M, et al. Heterozygous RELA mutations cause early-onset systemic lupus erythematosus by hijacking the NF-\u03baB pathway towards transcriptional activation of type-I interferon genes. 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