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Mendelian Susceptibility to Mycobacterial Disease Due to Il-12Rβ1 Deficiency in Three Iranian Children



Sarrafzadeh SA1 ; Mahloojirad M1 ; Nourizadeh M1 ; Casanova JL2, 3, 4, 6, 7 ; Pourpak Z1 ; Bustamante J2, 4, 5, 6 ; Moin M1
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Authors Affiliations
  1. 1. Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sante et de la Recherche Medicale, INSERM-U1163, Paris, France
  3. 3. Howard Hughes Medical Institute, NY, United States
  4. 4. Paris Descartes University, Imagine Institute, Paris, France
  5. 5. Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, Paris, France
  6. 6. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller branch, The Rockefeller University, New York, NY, United States
  7. 7. Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France

Source: Iranian Journal of Public Health Published:2016

Abstract

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare inheritance syndrome, characterized by a dissemi-nated infection with mycobacterium in children following BCG vaccination at birth. Regarding the vaccination pro-gram in Iran, it may consider as a public health problem. The pathogenesis of MSMD is dependent on either insuffi-cient production of IFN-gamma (γ) or inadequate response to it. Here, we want to introduce three cases including two siblings and one girl from two unrelated families with severe mycobacterial infections referred to Immunology, Asth-ma and Allergy Research Institute (IAARI), from 2013 to 2015; their MSMD was confirmed by both cytokine assess-ment and genetic analysis. Regarding the clinical features of the patients, cell proliferation against a mitogen and BCG antigen was ordered in a lymphocyte transformation test (LTT) setting. ELISA was performed for the measurement of IL-12p70 and IFN-γ in whole blood samples activated by BCG + recombinant human IFN-γ and BCG + recombi-nant human IL-12, respectively. In contrast to mitogen, the antigen-dependent proliferation activity of the patients’ leukocytes was significantly lower than that in normal range. We identified a homozygous mutation in IL12RB1 gene for two kindred who had a homozygous mutation affecting an essential splice site. For the third patient, a novel frameshift deletion in IL12RB1 gene was found. The genetic study results confirmed the impaired function of stimu-lated lymphocytes to release IFN-γ following stimulation with BCG+IL-12 while the response to rhIFN-γ for IL-12p70 production was relatively intact. Our findings show that cellular and molecular assessments are needed for pre-cise identification of immunodeficiency disorders especially those without clear-cut diagnostic criteria. © 2016, Iranian Journal of Public Health. All rights reserved.
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