Diseases associated with IRF8 include immunodeficiency 32A and immunodeficiency 32B.
AML: The transcription factor IRF8 has been identified as an AML-specific susceptibility gene in humans. IRF8 is upregulated in a subset of AML cells. Thus, high IRF8 expression is associated with a poorer prognosis of patients (Liss F et al. 2021). IRF8 regulates important signaling molecules such as the kinases SRC and FAK, the transcription factors RUNX1 and IRF5 as well as the cell cycle regulator cyclin D1.IRF8 could serve as a biomarker and potential molecular target in a subset of human AML in the future.
Immunodeficiency 32A (syn:IMD32A/ OMIM: 614893): autosomal dominant IRF8 deficiency causes an abnormal myeloid phenotype in peripheral blood with a marked loss of CD11C-positive dendritic cells. This dysfunction leads to a selective susceptibility to mycobacterial infections, an immune deficiency known as Mendelian susceptibility to mycobacterial disease (MSMD) (Hambleton et al. 2011). MSMD is a rare disorder characterized by a predisposition to disease caused by low virulent mycobacteria (e.g. BCG vaccines and environmental mycobacteria) in otherwise healthy individuals. MSMDs show no abnormalities in routine hematologic and immunologic tests. The term MSMD does not reflect all clinical features, as patients are also susceptible to salmonellosis, candidiasis and tuberculosis and, less frequently, infections with other intramacrophage bacteria, fungi or parasites and perhaps even some viruses.
Immunodeficiency 32B (syn:IMD32B/ OMIM: 226990): the autosomal recessive primary immunodeficiency characterized by recurrent infections resulting from variable defects in the development or function of immune cells, including monocytes, dendritic cells and natural killer (NK) cells. Patients are particularly susceptible to viral diseases (Mace et al. 2017).