Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2018 Oct;38(7):787-793.
doi: 10.1007/s10875-018-0548-1. Epub 2018 Sep 25.

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

Nioosha Nekooie-Marnany  1 , Caroline Deswarte  2   3 , Vajiheh Ostadi  1 , Bahram Bagherpour  1 , Elaheh Taleby  1 , Mazdak Ganjalikhani-Hakemi  1 , Tom Le Voyer  2   3 , Hamid Rahimi  4 , Jérémie Rosain  2   3   5 , Zahra Pourmoghadas  6 , Saba Sheikhbahaei  1 , Razieh Khoshnevisan  1 , Daniel Petersheim  7 , Daniel Kotlarz  7 , Christoph Klein  7 , Stéphanie Boisson-Dupuis  2   3   8 , Jean-Laurent Casanova  2   3   8   9   10 , Jacinta Bustamante  2   3   5   8 , Roya Sherkat  11
Affiliations
Case Reports

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

Nioosha Nekooie-Marnany et al. J Clin Immunol. 2018 Oct.

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 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.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest

The authors have no conflict of interest to declare.

Figures

Figure 1:
Figure 1:. IL-12Rβ1 expression in the cells of IL-12Rβ1 patients.
A. T-cell blasts from c.1172delC (P1), c.1791+2T>G (P2,3) and C.C962A (P4) patients and from healthy control (C+) were stained with IL-12Rβ1-specific mAbs (solid line) and isotype control antibodies (dashed line). B. Expression of IL-12Rβ1 protein in patients were indicated by fluorescence intensity (MFI). A p-value <0.05, <0.01 and <0.001 in one way Anowa is indicated by *, ** and ** Respectively. ns, not significant. NS, not stimulated
Figure 2:
Figure 2:. The IL-12 and IFN-γ responses on whole blood activation.
A. Production of IFN-γ (pg/mL) in response to Bacille Calmette–Guérin (BCG) and BCG+IL-12 in whole blood cells was quantified in patients with IL-12Rβ1 deficiency (P1, P2, P3 and P4). B. Production of IL-12 was assessed in supernants of whole blood activation by BCG and BCG+IFN-γ activation. C. TNF production was indicated in response to Lipopolysacharide (LPS) and LPS + IFN-γ. 1.II is the sister of P.1, C- is an IL-12Rβ1 deficient, ns, not significant. NS, not stimulated
See this image and copyright information in PMC

References

    1. Casanova J-L, Mendelian susceptibility to mycobacterial infection in man. Swiss medical weekly, 2001. 131(31-32): p. 445–454. - PubMed
    1. Flynn JL and Chan J, Immunology of tuberculosis. Annual review of immunology, 2001. 19(1): p. 93–129. - PubMed
    1. Feinberg J, et al. , Bacillus Calmette Guérin triggers the IL-12/IFN-γ axis by an IRAK-4- and NEMO-dependent, non-cognate interaction between monocytes, NK, and T lymphocytes. European journal of immunology, 2004. 34(11): p. 3276–3284. - PubMed
    1. Lee W-I, et al. , Immune defects in active mycobacterial diseases in patients with primary immunodeficiency diseases (PIDs). Journal of the Formosan Medical Association, 2011. 110(12): p. 750–758. - PubMed
    1. Bustamante J, et al. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity. in Seminars in immunology. Seminars in Immunology, 2014. 26(6): p. 454–470 - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources