Impaired IL-12-and IL-23-Mediated Immunity Due to IL-12R1 Deficiency in Iranian Patients with Mendelian Susceptibility to Mycobacterial Disease

Abstract

PurposeInborn 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-Guerin (BCG) vaccines and environmental, nontuberculous mycobacteria (NTM).MethodsIn 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-12R1 expression on T cell blasts, and sequenced candidate genes.ResultsWe report four patients from Isfahan, Iran, ranging from 3months to 26years 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-12R1 was completely abolished in the four patients with IL12RB1 mutations.ConclusionsIL-12R1 deficiency was found in the four MSMD Iranian families tested. It is the first report of an Iranian case with S321* mutant IL-12R1 protein. Mycobacterial osteomyelitis is another type of location of BCG infection in an IL-12R1-deficient patient, notified for the first time in this study.