Immunodeficiency 38 D84.8

Autosomal recessive immunodeficiency 38 (IMD38; see also Mendelian susceptibility to mycobacterial diseases) is a rare immunodeficiency syndrome caused by a mutation in the ISG15 gene (ISG15 stands for "ubiquitin like modifier"). ISG15 is a protein-coding gene located at chromosome 1p36.33. The protein encoded by this gene is a ubiquitin-like protein that attaches to intracellular target proteins upon activation by interferon-alpha and interferon-beta(ubiquitination).

The autosomal recessive ISG15 mutation causes a specific immune deficiency that results in severe clinical disease in affected individuals when infected with low virulence mycobacteria including Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccines (Bogunovic et al. 2012). In contrast, there is no immune deficiency to viral infections. Affected individuals exhibit intracranial calcification (Zhang et al. 2015).

1. Bogunovic D et al. (2012) Mycobacterial disease and impaired IFN-gamma immunity in humans with inherited ISG15 deficiency. Science 337: 1684-1688.
2. Zhang X et all. (2015) Human intracellular ISG15 prevents interferon-alpha/beta over-amplification and auto-inflammation. Nature 517: 89-93.