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J Clin Immunol. 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.

Author information

1
Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
2
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Imagine Institute, Necker Hospital for Sick Children, Paris, EU, France.
3
Paris Descartes University, Paris, EU, France.
4
Department of Pediatrics, Isfahan University of Medical Sciences, Isfahan, Iran.
5
Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris AP-HP, Necker Hospital for Sick Children, Paris, EU, France.
6
Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
7
Department of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Munich, EU, Germany.
8
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
9
Howard Hughes Medical Institute, New York, NY, USA.
10
Pediatric Hematology-Immunology Unit, Assistance Publique-Hôpitaux de Paris AP-HP, Necker Hospital for Sick Children, Paris, EU, France.
11
Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. sherkat@med.mui.ac.ir.

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

PMID:
30255293
DOI:
10.1007/s10875-018-0548-1

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