What We Have Here Is a Failure to Communicate: Interleukin-12 / Interferon-gamma Axis Defects and Mendelian Susceptibility to Mycobacterial Disease.

Abstract

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare group of immunodeficiencies with high mortality characterized by a failure of communication between phagocytic cells and their regulatory/support networks. The objective of this article was to review key aspects of MSMD management. A defective IL-12/IFN-γ circuit can result in overwhelming intracellular infection, leading to lymphadenopathy, organomegaly, and sepsis. In the setting of unexplained lymphadenopathy, early tissue and blood culture, with special attention to mycobacteria, is essential. If MSMD is suspected, genetic testing to assess for pathogenic variants affecting the IFN-γ/IL-12 signaling pathway is available. To date, at least 19 genes with hundreds of unique mutations have been identified; thus, genetic testing is essential to determine the specific defect and direct therapy. Multiple antibiotics, cytokine therapy in selected cases, and bone marrow transplantation should be considered.