Impaired IL-12- and IL-23-Mediated Immunity due to IL-12Rβ1 deficiency in Iranian Patients with Mendelian Susceptibility to Mycobacterial Disease

Abstract

Purpose.

Inborn errors of IFN- γ-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- γ, IL-12Rβ1 expression on T-cell blasts, and sequenced candidate genes.

Results.

We reported four patients from Isfahan, Iran, ranging from 3 months to 26 years old, who had impaired IL-12 signaling. All patients suffered from BCG infectious diseases. One of them presented mycobacterial osteomyelitis as a form of infection. By Sanger sequencing, we identified three different types of homozygous mutations in IL12RB1. Expression of IL-12Rβ1 was completely abolished in the four patients with IL12RB1 mutations.

Conclusions.

IL-12Rβ1 deficiency was found in the four MSMD Iranian families tested. It is the first report of an Iranian case with S321X mutant IL-12Rβ1 protein. Mycobacterial osteomyelitis is another type of location of mycobacterial infection in an IL-12Rβ1-deficient patient, notified for the first time in this study.