{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:42:16Z","timestamp":1790890936581,"version":"4.1.0"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T00:00:00Z","timestamp":1613692800000},"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":"<jats:p>Genetic mutations that result in loss-of-function of the protein A20 result in an early-onset autoinflammatory disease\u2014haploinsufficiency of A20 (HA20). The reported clinical presentations of HA20 include a Behcet\u2019s disease-like phenotype and a more lupus-like phenotype. We have identified a novel mutation in the gene encoding A20 in a pediatric patient with chronic lymphadenopathy, lupus-like symptoms, and progressive hypogammaglobulinemia. This case illustrates the wide range of clinical symptoms, including immunodeficiency, that can occur in patients with HA20.<\/jats:p>","DOI":"10.3389\/fimmu.2021.629457","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T04:47:06Z","timestamp":1613710026000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Case Report: A Novel TNFAIP3 Mutation Causing Haploinsufficiency of A20 With a Lupus-Like Phenotype"],"prefix":"10.3389","volume":"12","author":[{"given":"Zachary R.","family":"Shaheen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J. A.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce A.","family":"Binstadt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)77165-2","article-title":"The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein","volume":"265","author":"Opipari","year":"1990","journal-title":"J Biol Chem"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5488.2350","article-title":"Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice","volume":"289","author":"Lee","year":"2000","journal-title":"Sci (N Y NY)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nature02794","article-title":"De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling","volume":"430","author":"Wertz","year":"2004","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.it.2013.10.005","article-title":"A20 in inflammation and autoimmunity","volume":"35","author":"Catrysse","year":"2014","journal-title":"Trends Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/ng.3459","article-title":"Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease","volume":"48","author":"Zhou","year":"2016","journal-title":"Nat Genet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1016\/j.jaci.2017.10.039","article-title":"Haploinsufficiency of A20 causes autoinflammatory and autoimmune disorders","volume":"141","author":"Kadowaki","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-019-00288-6","article-title":"Haploinsufficiency of A20 (HA20): updates on the genetics, phenotype, pathogenesis and treatment","volume":"16","author":"Yu","year":"2019","journal-title":"World J Pediatr WJP"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-212403","article-title":"A20 haploinsufficiency (HA20): clinical phenotypes and disease course of patients with a newly recognised NF-kB-mediated autoinflammatory disease","volume":"77","author":"Aeschlimann","year":"2018","journal-title":"Ann Rheumatic Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-020-00792-9","article-title":"Haploinsufficiency of A20 Due to Novel Mutations in TNFAIP3","volume":"40","author":"He","year":"2020","journal-title":"J Clin Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-15-178","article-title":"The effect of rituximab therapy on immunoglobulin levels in patients with multisystem autoimmune disease","volume":"15","author":"Marco","year":"2014","journal-title":"BMC Musculoskeletal Disord"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2014.11.009","article-title":"Rituximab-associated hypogammaglobulinemia: incidence, predictors and outcomes in patients with multi-system autoimmune disease","volume":"57","author":"Roberts","year":"2015","journal-title":"J Autoimmun"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.03022","article-title":"Identification of Novel Genetic Variants in CVID Patients With Autoimmunity, Autoinflammation, or Malignancy","volume":"10","author":"Christiansen","year":"2019","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.09.038","article-title":"Haploinsufficiency of TNFAIP3 (A20) by germline mutation is involved in autoimmune lymphoproliferative syndrome","volume":"139","author":"Takagi","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.234","article-title":"A20 is targeted by promoter methylation, deletion and inactivating mutation in MALT lymphoma","volume":"24","author":"Chanudet","year":"2010","journal-title":"Leukemia"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.02.001","article-title":"Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma","volume":"27","author":"Sharpe","year":"2015","journal-title":"Cancer Cell"},{"key":"B16","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1002\/eji.201041313","article-title":"A20 deficiency in B cells enhances B-cell proliferation and results in the development of autoantibodies","volume":"41","author":"H\u00f6velmeyer","year":"2011","journal-title":"Eur J Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.07.017","article-title":"The ubiquitin modifying enzyme A20 restricts B cell survival and prevents autoimmunity","volume":"33","author":"Tavares","year":"2010","journal-title":"Immunity"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.629457\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T04:47:08Z","timestamp":1613710028000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.629457\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,19]]},"references-count":17,"alternative-id":["10.3389\/fimmu.2021.629457"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.629457","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,19]]},"article-number":"629457"}}