A Heterozygous Gain-of-Function Variant in IKBKB Associated with Autoimmunity and Autoinflammation.

ABSTRACT:

Purpose

Biallelic loss-of-function variants in IKBKB cause severe combined immunodeficiency. We describe a case of autoimmunity and autoinflammation in a male infant with a heterozygous gain-of-function (GOF) IKBKB variant.

Methods

Case report and review of the literature. We performed in silico variant analysis, measurement of plasma soluble biomarkers associated with immune activation, functional stimulation of patient peripheral blood mononuclear cells, and functional validation of variants transduced in Jurkat cells.

Results

A patient with two heterozygous IKBKB variants (E518K and T559M) presents with previously undescribed autoimmune cytopenias and autoinflammation. He had decreased TNF-α-induced IkBα degradation in vitro, and had increased serum biomarkers asso

SUBMITTER: Sacco K 

PROVIDER: S-EPMC10362980 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature