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Vol. 47. Issue 1.
Pages 38-42 (January - February 2019)
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Vol. 47. Issue 1.
Pages 38-42 (January - February 2019)
Original Article
DOI: 10.1016/j.aller.2018.06.005
Evaluation of interleukin-12 receptor β1 and interferon gamma receptor 1 deficiency in patients with disseminated BCG infection
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B. Pourakbaria, R. Hosseinpour Sadeghia, S. Mahmoudia, N. Parvaneha, S. Keshavarz Valianb, S. Mamishia,c,
Corresponding author
smamishi@sina.tums.ac.ir

Corresponding author.
a Pediatric Infectious Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
b School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
c Department of Infectious Diseases, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
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Abstract
Introduction

Disseminated BCG infections among other complications of Bacillus Calmette–Guérin (BCG) vaccine are rare and have occurred in children with immunodeficiency disorders such as mendelian susceptibility to mycobacterial disease (MSMD) which could be due to defects in some elements of IL-12/IFN-γ axis. MSMD-causing mutations have been identified in 10 genes during the last two decades. Among them, mutations in the IL12Rβ1 and IFNγR1 genes constitute about 80% of recorded cases of MSMD syndrome. The aim of this study was to investigate IL-12Rβ1 and IFN-γR1 deficiencies in patients with disseminated BCG infection.

Methods

This study was performed on 31 children with disseminated BCG infections who referred to children's medical center. Whole blood cell culture was performed in presence of BCG, IL-12 and IFN-γ stimulators. The supernatants were assayed for IFN-γ and IL-12p70 by ELISA method. In order to evaluate IL12Rβ1 and IFN-γR1 receptors expression, flow cytometry staining was performed on the patients’ T-cells stimulated with PHA.

Results

Flow cytometry staining of 31 Iranian patients with disseminated BCG infections with the average age of 43 months showed lack of the expression of IL-12Rβ1 and IFN-γR1 genes in PHA-T-cells of the nine and one patients, respectively in whom the incomplete production of IFN-γ and IL-12 was reported by ELISA. Among these 10 patients, eight cases had related parents (80%).

Conclusion

It is recommended that to avoid BCG complications, screening be performed for MSMD before BCG inoculation in individuals with positive family history of primary immunodeficiency diseases and inhabitants of areas with high frequency of consanguinity.

Keywords:
Disseminated BCG infection
MSMD
IL-12Rβ1
IFN-γR1

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