Impaired IL-12- and IL-23-Mediated Immunity Due to IL-12R?1 Deficiency in Iranian Patients with Mendelian Susceptibility to Mycobacterial Disease.

ABSTRACT: PURPOSE:Inborn errors of IFN-?-mediated immunity underlie Mendelian Susceptibility to Mycobacterial Disease (MSMD), which is characterized by an increased susceptibility to severe and recurrent infections caused by weakly virulent mycobacteria, such as Bacillus Calmette-Guérin (BCG) vaccines and environmental, nontuberculous mycobacteria (NTM). METHODS:In this study, we investigated four patients from four unrelated consanguineous families from Isfahan, Iran, with disseminated BCG disease. We evaluated the patients' whole blood cell response to IL-12 and IFN-?, IL-12R?1 expression on T cell blasts, and sequenced candidate genes. RESULTS:We report four patients from Isfahan, Iran, ranging from 3 months to 26 years old, with impaired IL-12 signaling. All patients suffered from BCG disease. One of them presented mycobacterial osteomyelitis. By Sanger sequencing, we identified three different types of homozygous mutations in IL12RB1. Expression of IL-12R?1 was completely abolished in the four patients with IL12RB1 mutations. CONCLUSIONS:IL-12R?1 deficiency was found in the four MSMD Iranian families tested. It is the first report of an Iranian case with S321* mutant IL-12R?1 protein. Mycobacterial osteomyelitis is another type of location of BCG infection in an IL-12R?1-deficient patient, notified for the first time in this study.

SUBMITTER: Nekooie-Marnany N 

PROVIDER: S-EPMC6469360 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature