Case Report: A patient with a novel heterozygous IRF8 variant with repeated infection and immune-mediated organ disease, but without disseminated mycobacterial disease despite BCG immunization.

ABSTRACT: We describe a patient with a novel, de novo heterozygous IRF8 variant (c.1182dup) who presented with viral and bacterial susceptibility, lymphoproliferation, and liver and lung diseases characteristically seen in patients with underlying inborn errors of immunity, but without disseminated mycobacterial disease, despite vaccination with Bacillus Calmette-Guérin (BCG), the live attenuated vaccine form of Mycobacterium bovis. Laboratory evaluation revealed an absence of circulating plasmacytoid dendritic cells (pDC) with poor IL-12p70 and IFN-γ secretion upon LPS stimulation, and poor IFN-γ secretion upon PHA stimulation. In contrast, another patient with a different novel, de novo heterozygous IRF8 variant (c.10C>T) had milder early life infection susceptib

SUBMITTER: Chiang SCC 

PROVIDER: S-EPMC12602488 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature