Haploinsufficiency of A20 Due to Novel Mutations in TNFAIP3.
J Clin Immunol
; 40(5): 741-751, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32514655
ABSTRACT
Haploinsufficiency of A20 (HA20) is a newly described immune dysregulation disease due to the loss-of-function mutation in TNFAIP3. In the present study, we report six patients from four unrelated Chinese families with distinct pathogenic mutations in TNFAIP3, including three novel variants. All of the patients presented with early-onset autoimmune/auto-inflammatory diseases, including Crohn's disease, Behcet's disease, systemic lupus erythematosus, and unclassified auto-inflammatory syndrome. Immunological phenotype tests showed elevated levels of serum pro-inflammatory cytokines, reduced naïve B cells and TFH cells, an inverted CD4CD8 ratio, and increased susceptibility to restimulation-induced cell death (RICD) and FASL-induced apoptosis in derived T cells. Insufficient expression of A20 was found in these patients. A20 truncated protein was detected in mutant-transfected 293T cells. Upon TNF-α stimulation, the NF-κB pathway was over-activated in both derived T cells of these patients and mutant-transfected Hela cells. In conclusion, clinical manifestations are diverse in patients with HA20, even in those with the same TNFAIP3 mutation. A20 inhibits the NF-κB pathway and plays a crucial role in the regulation of cell death. Haploinsufficiency of A20 leads to defects in both innate and adaptive immunity.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Doença de Crohn
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Síndrome de Behçet
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Proteína 3 Induzida por Fator de Necrose Tumoral alfa
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Mutação com Perda de Função
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Lúpus Eritematoso Sistêmico
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
J Clin Immunol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China