Haploinsufficiency of A20 Due to Novel Mutations in TNFAIP3.

Journal of Clinical Immunology
Tingyan HeJun Yang

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 CD4:CD8 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....Continue Reading

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Citations

Mar 9, 2021·Frontiers in Immunology·Zachary R ShaheenBryce A Binstadt
May 10, 2021·Liver International : Official Journal of the International Association for the Study of the Liver·Samuel DeshayesAchille Aouba

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Methods Mentioned

BETA
Transfection
PCR
flow cytometry
exome sequencing

Software Mentioned

Swiss
MutationTaster
PolyPhen
GERP
FlowJo
MutationTaster MT
GraphPad
Model
GraphPad Prism
Prism

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