NFκB pathway dysregulation due to reduced RelB expression leads to severe autoimmune disorders and declining immunity.

ABSTRACT:

Background

Genetic aberrations in the NFκB pathway lead to primary immunodeficiencies with various degrees of severity. We previously demonstrated that complete ablation of the RelB transcription factor, a key component of the alternative pathway, results in an early manifested combined immunodeficiency requiring stem cell transplantation.

Objective

To study the molecular basis of a progressive severe autoimmunity and immunodeficiency in three patients.

Methods

Whole exome sequencing was performed to identify the genetic defect. Molecular and cellular techniques were utilized to assess the variant impact on NFκB signaling, canonical and alternative pathway crosstalk, as well as the resultant effects on immune function.

Results

Patients presented with multiple a

SUBMITTER: Sharfe N 

PROVIDER: S-EPMC10861023 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature