Juvenile onset autoinflammatory disease due to a novel mutation in TNFAIP3 (A20)

Sato, Shuzo; Fujita, Yuya; Shigemura, Tomonari; Matoba, Hisanori; Agematsu, Kazunaga; Sumichika, Yuya; Yashiro, Makiko; Ono, Atsushi; Kawasaki, Yukihiko; Kobayashi, Hiroko; Watanabe, Hiroshi; Koga, Tomohiro; Kawakami, Atsushi; Migita, Kiyoshi

doi:10.1186/s13075-018-1766-x

Cited by 13 publications

(7 citation statements)

References 8 publications

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“…1 ) who suffered from recurrent painful oral ulcers, epigastralgia, and a low-grade fever. His mother and sister also had oral and genital ulcers, and his sister was suspected of presenting with BD symptoms ( 31 ). Treatment with prednisolone relieved the clinical symptoms and improved the inflammation in this patient, and an investigation of the effects of this mutation in peripheral blood mononuclear cells (PBMCs) from this patient showed that the expression of A20 and IκB-α was suppressed, regardless of TNF-α administration ( Fig.…”

Section: Behçet's Disease (Bd) and Bd-like Syndromesmentioning

confidence: 99%

“…1 ). These findings imply that haploinsufficiency of TNFAIP3, which leads to an impaired A20 expression, may be responsible for the exacerbated TNF-α mediated inflammation with BD-like symptoms ( 31 ). Nevertheless, data from a larger number of HA20 patients will be needed to catalog the clinical features and outcomes of this condition.…”

Section: Behçet's Disease (Bd) and Bd-like Syndromesmentioning

confidence: 99%

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The Expanding Spectrum of Autoinflammatory Diseases

et al. 2023

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Autoinflammatory diseases are systemic disorders caused by genetic or acquired abnormalities in certain signaling pathways of the innate immune system. Dysregulated activation of the inflammasome, i.e. molecular platforms responsible for the activation of caspase-1 and production of interleukin-1β, causes autoinflammation. Familial Mediterranean fever (FMF), the most common genetic autoinflammatory disease, is characterized by a periodic fever and serositis. The complex and heterogeneous genetic background of Japanese FMF patients, accompanied by potential overlap with other rheumatic diseases, suggests crosstalk between genetic and environmental factors. Recently, FMF has been recognized as being part of a spectrum of autoinflammatory syndromes named pyrin-associated autoinflammatory diseases. The discovery of a new monogenic autoinflammatory disease, A20 haploinsufficiency, may provide novel insights into early-onset Behçet's-like diseases. In contrast, adult-onset Still's disease and Schnitzler's syndrome are acquired autoinflammatory diseases without a monogenic abnormality. Although the concept of autoinflammatory diseases originally applied to monogenic hereditary recurrent fevers, it has been expanded to include non-genetic complex autoinflammatory diseases. Information concerning monogenic autoinflammatory diseases may prove useful for elucidating the molecular mechanisms underlying non-genetic autoinflammatory diseases.

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Section: Behçet's Disease (Bd) and Bd-like Syndromesmentioning

confidence: 99%

Section: Behçet's Disease (Bd) and Bd-like Syndromesmentioning

confidence: 99%

The Expanding Spectrum of Autoinflammatory Diseases

et al. 2023

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“…It is not therefore surprising that HA20 can be associated with a wide array of clinical presentations from a Behçet’s-like syndrome characterized by systemic inflammation, oral and genital ulceration, arthralgia/arthritis and ocular symptoms, to autoinflammatory conditions such as sJIA and adult-onset Still’s disease, to classic autoimmune conditions including SLE [38, 43–45]. Patients with autoimmune lymphoproliferative syndrome-like condition and a label of undifferentiated complex autoimmune disease have also been described, illustrating the complexity of phenotypes associated with this condition.…”

Section: Relopathiesmentioning

confidence: 99%

Hereditary systemic autoinflammatory diseases and Schnitzler’s syndrome

2019

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The systemic autoinflammatory diseases are disorders of the innate immune system distinguished by severe inflammation resulting from dysregulation of the innate immune system. Hereditary fever syndromes, such as FMF, TNF receptor-associated periodic syndrome, cryopyrin-associated periodic syndromes and mevalonate kinase deficiency, were the first group of systemic autoinflammatory diseases for which a genetic basis was established, between 1999 and 2001. Currently according to the latest report of the international union of immunological societies, 37 separate monogenic disorders were classified as autoinflammatory. In addition to the abovementioned monogenic conditions, we describe Schnitzler’s syndrome, a well-defined, acquired autoinflammatory condition without a clear genetic basis. For the purposes of this review, we discuss several conditions defined by the latest consensus process as systemic autoinflammatory diseases. We focus on those disorders where recent studies have contributed to further phenotypic characterization or had an impact on clinical management.

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“…4,8,9 Moreover, some investigators have found that tumor necrosis factor a-induced protein 3 (TNFAIP3; also known as A20) mutations may cause systemic inflammatory disease. 10 Authors of a molecular study further showed that TNFAIP3 (A20) was dysregulated in pediatric CD, 11,12 indicating that TNFAIP3 (A20) is a key player in the inflammation associated with pediatric CD. 11 Therefore, investigating the status of TNFAIP3 (A20) in children with CD could allow new insights into Longitudinal ulcers (A) and mildly cobblestone-like appearance of the colonic mucosa (B) from colonoscopy images.…”

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confidence: 99%

Knee Joint Swelling at Presentation: A Case of Pediatric Crohn Disease With a TNFAIP3 Mutation

et al. 2020

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Crohn disease (CD) is a chronic inflammatory disease, and its incidence in children is rising. Despite extensive reports and investigations, the pathogenesis of CD has not been clearly elucidated, particularly in regard to triggering factors. A genetic predisposition is considered important when investigating the mechanism leading to CD, and the discovery of new CD-associated genes has increased our understanding of its immunopathogenesis and improved the efficacy of its treatment of CD. Early detection and treatment (eg, as children) with gene-based precision therapy can effectively prevent complications related to CD. In this case, a Chinese Han boy with CD associated with a mutation of tumor necrosis factor α-induced protein 3 was treated with recombinant human tumor necrosis factor-a receptor II:IgG Fc fusion protein. We suspected the boy had CD because of chronic abdominal pain, aphthous stomatitis, moderate anemia, a high erythrocyte sedimentation rate (36–79 mm/h), multiple intestinal ulcers, knee joint swelling, and a tumor necrosis factor α-induced protein 3 mutation. After total enteral nutrition and hormone therapy for 5 months, his abdominal pain and joint symptoms did not improve, so we started gene-based precision therapy with recombinant human tumor necrosis factor-a receptor II: IgG Fc fusion protein, which may play an important role in restricting TNF-α-induced NF-κB signaling. After 3 weeks, inflammation indicators were within the normal range, and multiple ulcers and joint symptoms were relieved. The present case demonstrates a safe therapeutic schedule that leads to rapid improvements in the clinical and biochemical status of patients with CD.

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Juvenile onset autoinflammatory disease due to a novel mutation in TNFAIP3 (A20)

Cited by 13 publications

References 8 publications

The Expanding Spectrum of Autoinflammatory Diseases

The Expanding Spectrum of Autoinflammatory Diseases

Hereditary systemic autoinflammatory diseases and Schnitzler’s syndrome

Knee Joint Swelling at Presentation: A Case of Pediatric Crohn Disease With a TNFAIP3 Mutation

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