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

J Clin Immunol. 2018 Oct;38(7):787-793. doi: 10.1007/s10875-018-0548-1. Epub 2018 Sep 25.


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 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-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 S321* mutant IL-12Rβ1 protein. Mycobacterial osteomyelitis is another type of location of BCG infection in an IL-12Rβ1-deficient patient, notified for the first time in this study.

Keywords: (BCG)-osis; Bacillus Calmette–Guérin vaccination; IL-12; Mendelian susceptibility to mycobacterial disease; interferon.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • BCG Vaccine / immunology
  • Biomarkers
  • Child
  • Child, Preschool
  • Disease Susceptibility*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Immunophenotyping
  • Infant
  • Interleukin-12 / metabolism*
  • Interleukin-23 / metabolism*
  • Iran / epidemiology
  • Male
  • Mutation
  • Mycobacterium Infections / epidemiology
  • Mycobacterium Infections / etiology*
  • Mycobacterium Infections / metabolism*
  • Mycobacterium Infections / prevention & control
  • Prognosis
  • Receptors, Interleukin-12 / deficiency*
  • Young Adult


  • BCG Vaccine
  • Biomarkers
  • IL12RB1 protein, human
  • Interleukin-23
  • Receptors, Interleukin-12
  • Interleukin-12