title: Mendelian Susceptibility to Mycobacterial Disease due to IL-12Rβ1 Deficiency in Three Iranian Children.
abstract: Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare inheritance syndrome, characterized by a disseminated infection with mycobacterium in children following BCG vaccination at birth. Regarding the vaccination program in Iran, it may consider as a public health problem. The pathogenesis of MSMD is dependent on either insufficient 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, Asthma and Allergy Research Institute (IAARI), from 2013 to 2015; their MSMD was confirmed by both cytokine assessment 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 + recombinant 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 stimulated 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 precise identification of immunodeficiency disorders especially those without clear-cut diagnostic criteria.
authors.affiliation: Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shokouh Azam
authors.initials: SA
authors.lastname: Sarrafzadeh
authors.affiliation: Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Mahloojirad
authors.affiliation: Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Nourizadeh
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, INSERM-U1163, Paris, France; Howard Hughes Medical Institute, NY, USA; Paris Descartes University, Imagine Institute, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller branch, the Rockefeller University, New York, NY, USA; Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France.
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.affiliation: Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Pourpak
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, INSERM-U1163, Paris, France; Paris Descartes University, Imagine Institute, Paris, France; Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller branch, the Rockefeller University, New York, NY, USA.
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
authors.affiliation: Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Moin
keywords: IL-12Rβ1 Deficiency; Interfron-gamma; Interleukin 12; Mendelian; Mycobacterium