Mendelian susceptibility to mycobacterial disease: Clinical and immunological findings of patients suspected for IL12Rβ1 deficiency

Allergol Immunopathol (Madr). 2019 Sep-Oct;47(5):491-498. doi: 10.1016/j.aller.2019.02.004. Epub 2019 Jul 23.

Abstract

Background: Mendelian susceptibility to mycobacterial disease (MSMD) is characterized by increased susceptibility to weakly virulent mycobacteria (Bacillus Calmette-Guérin [BCG] vaccines and environmental mycobacteria), Mycobacterium tuberculosis, Candida spp. and Salmonella spp. The aim of this study is to evaluate clinical features and immunological findings of MSMD patients with interleukin 12 receptor beta 1 (IL12Rβ1) deficiency.

Methods: Among 117 screened patients with BCG infection following vaccination, 23 suspected MSMD subjects were recruited to this study by the exclusion of severe combined immunodeficiencies and chronic granulomatous diseases. Flow cytometric assessment for surface expression of IL12Rβ1 was performed. Moreover, the clinical and immunological data from the patients was evaluated.

Results: A significant decrease (less than 1%) in the surface expression of IL12Rβ1 was reported in six cases which showed a significant increase in the count of lymphocytes (p=0.009) and CD8+ T cells (p=0.008) as compared to MSMD subjects with normal expression of surface IL12Rβ1. The frequency of disseminated BCGosis (50% vs. 20%, p=0.29), recurrent infection (83.3% vs. 40%, p=0.14) and salmonellosis (33.3% vs. 0.0%, p=0.07) was higher in IL12Rβ1 deficient subjects than IL12Rβ1 sufficient individuals.

Conclusion: MSMD patients with childhood onset of mycobacteriosis (mostly after BCG vaccination) and recurrent salmonellosis could be evaluated for IL12Rβ1 expression with flow cytometry for punctual diagnosis.

Keywords: IL12Rβ1; Mendelian susceptibility to mycobacterial diseases; Primary immunodeficiency; Vaccination side effects.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Female
  • Genetic Predisposition to Disease
  • Herpes Simplex / genetics
  • Herpes Simplex / immunology*
  • Humans
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / immunology*
  • Infant
  • Male
  • Mutation / genetics*
  • Mycobacterium Infections, Nontuberculous / genetics
  • Mycobacterium Infections, Nontuberculous / immunology*
  • Mycobacterium bovis / immunology*
  • Prospective Studies
  • Receptors, Interleukin-12 / genetics*
  • Receptors, Interleukin-12 / metabolism
  • Simplexvirus / physiology*

Substances

  • IL12RB1 protein, human
  • Receptors, Interleukin-12