Immunodeficiency 32AD81.4

The very rare immunodeficiency 32A is caused by an autosomal dominant IRF8 deficiency.

This deficiency causes an abnormal myeloid phenotype in the peripheral blood with a marked loss of CD11C-positive dendritic cells.

The dysfunction results in selective susceptibility to mycobacterial infections, an immune deficiency termed Mendelian susceptibility to mycobacterial diseases -MSMD (Hambleton et al. 2011).

MSMD is a rare disease characterized by a predisposition to disease caused by low virulence mycobacteria (e.g., BCG vaccines and environmental mycobacteria) in otherwise healthy individuals. MSMD do not show abnormalities in routine hematological and immunological tests.

The designation MSMD does not reflect all clinical features, as patients are also susceptible to salmonellosis, candidiasis, and tuberculosis, and less commonly to infections with other intramacrophageous bacteria, fungi, or parasites, and perhaps even some viruses.

Lit

1. Bustamante J et al (2014) Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity. Semin Immunol 26:454-470.
2. DiNardo CD et al.(2016) Mutations in AML: prognostic and therapeutic implications. Hematol. Am Soc Hematol Educ Program 2016:348-355.
3. Hambleton S et al (2011) IRF8 mutations and human dendritic-cell immunodeficiency. New Eng. J Med 365: 127-138.
4. Liss F et al (2021) IRF8 Is an AML-Specific Susceptibility Factor That Regulates Signaling Pathways and Proliferation of AML Cells. Cancers (Basel) 13:764.
5. Mace EM et al (2017) Biallelic mutations in IRF8 impair human NK cell maturation and function. J Clin Invest 127: 306-320.