Impaired in-vitro responses to IL-12 and IFN-γ in Iranian patients with Mendelian susceptibility to mycobacterial disease

Allergol Immunopathol (Madr). 2015 Sep-Oct;43(5):456-60. doi: 10.1016/j.aller.2014.05.008. Epub 2014 Sep 6.

Abstract

Introduction: Diagnosis of specific molecular defects of Mendelian susceptibility to mycobacterial diseases (MSMD) patients is important with respect to their clinical outcomes and their response to therapy. The aim of this study was to perform functional tests on blood samples of a group of patients who were suspected of having MSMD.

Methods: This study was performed on 11 cases who had mycobacterial infections and suspected MSMD. Whole blood cell culture was performed in presence of different stimulators. The supernatants were assayed for IFN-γ, IL-12p40 by ELISA method.

Results: All patients presented with complications of BCG vaccine in the form of localised lymphadenitis or disseminated BCG infection and chronic mycobacterial osteomyelitis. Infections with Salmonella species occurred in two patients. In-vitro studies showed that 10 cases had impaired response to IL-12. However, the baseline levels of IL-12p40 were normal, while one of our patients may have a potential IFN-γ signalling defect or an IL-12p40 defect.

Conclusions: Early detection of MSMD and commencing of appropriate combination therapy could prevent severe or even fatal complications of uncontrolled mycobacterial infections.

Keywords: Immunodeficiency; Mendelian susceptibility to mycobacterial diseases; Mycobacterial diseases.

MeSH terms

  • Biomarkers / blood
  • Child, Preschool
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Infant
  • Interferon-gamma / blood
  • Interferon-gamma / immunology*
  • Interleukin-12 Subunit p40 / blood
  • Interleukin-12 Subunit p40 / immunology*
  • Iran
  • Male
  • Mycobacterium Infections, Nontuberculous / blood
  • Mycobacterium Infections, Nontuberculous / immunology*

Substances

  • Biomarkers
  • Interleukin-12 Subunit p40
  • Interferon-gamma