In:
Science Immunology, American Association for the Advancement of Science (AAAS), Vol. 7, No. 74 ( 2022-08-12)
Abstract:
TRAF3 is a cytoplasmic adaptor protein involved in multiple intracellular signal transduction pathways. Rae et al. identified nine individuals with a previously undescribed monogenic immune dysregulatory syndrome caused by a loss-of-function mutation in one of their two TRAF3 alleles. Patients with this newly described TRAF3 haploinsufficiency syndrome exhibited B cell hyperactivity leading to hypergammaglobulinemia and autoimmunity but also displayed increased susceptibility to recurrent bacterial infections. Common human genetic variants of TRAF3 associated with lower gene expression were found to carry an increased risk of autoimmune disease and some B cell malignancies. These findings point to functional impairment of TRAF3 as a shared mechanism leading to B cell dysfunction, hyperactivity, and disease in the presence of either rare loss-of-function germline mutations or much more common genetic variants.
Type of Medium:
Online Resource
ISSN:
2470-9468
DOI:
10.1126/sciimmunol.abn3800
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2022
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