TNFAIP3 haploinsufficiency is the cause of autoinflammatory manifestations in a patient with a deletion of 13Mb on chromosome 6

被引：32

作者：

Franco-Jarava, Clara ^{[1
,2
]}

Wang, Hongying ^{[3
]}

Martin-Nalda, Andrea ^{[2
,4
]}

Daniel Alvarez, de la Sierra ^{[1
]}

Garcia-Prat, Marina ^{[2
,4
]}

Bodet, Domingo ^{[5
]}

Garcia-Patos, Vicenc ^{[5
]}

Plaja, Alberto ^{[6
]}

Rudilla, Francesc ^{[7
]}

Rodriguez-Sureda, Victor ^{[8
,9
]}

Garcia-Latorre, Laura ^{[8
,10
]}

Aksentijevich, Ivona ^{[3
]}

Colobran, Roger ^{[1
,2
,6
]}

Soler-Palacin, Pere ^{[2
,4
,11
]}

机构：

[1] Hosp Univ Vall dHebron, Vall dHebron Res Inst VHIR, Immunol Dept, Diagnost Immunol, Barcelona, Spain

[2] Jeffrey Modell Diagnost & Res Ctr Primary Immunod, Barcelona, Spain

[3] NHGRI, Inflammatory Dis Sect, Bethesda, MD 20892 USA

[4] Hosp Univ Vall dHebron, Infect Immunocompromised Pediat Patients, Vall dHebron Res Inst VHIR, Pediat Infect Dis & Immunodeficiencies Unit, Barcelona, Spain

[5] Hosp Univ Vall dHebron, Dermatol Dept, Barcelona, Spain

[6] Hosp Univ Vall dHebron, Genet Dept, Barcelona, Spain

[7] Banc Sang & Teixits Catalunya, Barcelona, Spain

[8] Univ Autonoma Barcelona, Vail dHebron Inst Recerca, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Drug Delivery & Targeting Grp, Barcelona, Spain

[9] Inst Salud Carlos III, Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Madrid, Spain

[10] Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBER ER, Madrid, Spain

[11] UAB, Med Dept, Barcelona, Spain

来源：

CLINICAL IMMUNOLOGY | 2018年 / 191卷

关键词：

Autoinflanunatory diseases; Behcet's disease; TNFAIP3; Comparative Genomic Hybridization (CGH); Chromosome deletion; Oral ulcer; BEHCETS-DISEASE; NLRP3; INFLAMMASOME; UBIQUITINATION; SUSCEPTIBILITY; DISORDERS; MUTATIONS; RECEPTOR; DOMAINS; FAMILY;

D O I：

10.1016/j.clim.2018.03.009

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

There is scarce literature about autoinflammation in syndromic patients. We describe a patient who, in addition to psychomotor and growth delay, presented with fevers, neutrophilic dermatosis, and recurrent orogenital ulcers. Comparative Genomic Hybridization (CGH) array permitted to identify a 13.13Mb deletion on chromosome 6, encompassing 53 genes, and including TNFAIP3 gene (A20). A20 is a potent inhibitor of the NF-kB signalling pathway and restricts inflammation via its deubiquitinase activity. Western blotting and immunoprecipitation assays showed decreased A20 expression and increased phosphorylation of p65 and IkBa. Patient's cells displayed increased levels of total K63-linked ubiquitin and increased levels of ubiquitinated RIP and NEMO after stimulation with TNF. We describe the molecular characterization of an autoinflammatory disease due to a large chromosomal deletion and review the phenotypes of patients with A20 haploinsufficiency. CGH arrays should be the first diagnostic method for comprehensive analysis of patients with syndromic features and immune dysregulation.

引用

页码：44 / 51

页数：8

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