Faculty Opinions recommendation of Mendelian susceptibility to mycobacterial disease: 2014-2018 update.

Abstract

Mendelian susceptibility to mycobacterial disease (MSMD) is caused by inborn errors of IFN-γ immunity. Since 1996, disease-causing mutations have been found in 11 genes, which, through allelic heterogeneity, underlie 21 different genetic disorders. We briefly review here progress in the study of molecular, cellular and clinical aspects of MSMD since the last comprehensive review published in 2014. Highlights include the discoveries of (i) a new genetic etiology, autosomal recessive SPPL2a deficiency, (ii) TYK2-deficient patients with a clinical phenotype of MSMD, (iii) an allelic form of partial recessive IFN-γR2 deficiency, and (iv) two forms of syndromic MSMD: RORγ/RORγT and JAK1 deficiencies. These recent findings illustrate how genetic and immunological studies of MSMD can shed a unique light onto the mechanisms of protective immunity to mycobacteria in humans.