TY - JOUR
T1 - Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases
T2 - Experience From India
AU - Taur, Prasad D.
AU - Gowri, Vijaya
AU - Pandrowala, Ambreen Abdulwahab
AU - Iyengar, Vaishnavi V.
AU - Chougule, Akshaya
AU - Golwala, Zainab
AU - Chandak, Shraddha
AU - Agarwal, Reepa
AU - Keni, Purva
AU - Dighe, Neha
AU - Bodhanwala, Minnie
AU - Prabhu, Shakuntala
AU - George, Biju
AU - Fouzia, N. A.
AU - Edison, Eunice Sindhuvi
AU - Arunachalam, Arun Kumar
AU - Madkaikar, Manisha Rajan
AU - Dalvi, Aparna Dhondi
AU - Yadav, Reetika Malik
AU - Bargir, Umair Ahmed
AU - Kambli, Priyanka Madhav
AU - Rawat, Amit
AU - Das, Jhumki
AU - Joshi, Vibhu
AU - Pilania, Rakesh Kumar
AU - Jindal, Ankur Kumar
AU - Bhat, Sunil
AU - Bhattad, Sagar
AU - Unni, Jeeson
AU - Radhakrishnan, Nita
AU - Raj, Revathi
AU - Uppuluri, Ramya
AU - Patel, Shivani
AU - Lashkari, Harsha Prasada
AU - Aggarwal, Amita
AU - Kalra, Manas
AU - Udwadia, Zarir
AU - Bafna, Vibha Sanjay
AU - Kanade, Tarun
AU - Puel, Anne
AU - Bustamante, Jacinta
AU - Casanova, Jean Laurent
AU - Desai, Mukesh M.
N1 - Funding Information:
We would like to acknowledge Dr. Zinet Currimbhoy who started the Immunology Department at B. J. Wadia Hospital for Children in early 2000s and continues to support and mentor the department. We thankfully acknowledge Foundation for Primary Immunodeficiencies, USA for providing a platform to collate and present the data regarding MSMD in India. We acknowledge Indian Council of Medical Research (ICMR), New Delhi, India for funding the Centre of Excellence in PID (vide Grant No. 61/02/2012/IMM/BMS) which supports the diagnostic workup of the cases. However, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would also like to thank Dr. Dinakantha Kumararatne, Cambridge University, who helped us with the diagnosis of our first case of IL12RB1 defect. The Laboratory of Human Genetics of Infectious Diseases is supported in part by institutional grants from INSERM, University of Paris, The Rockefeller University and the St. Giles Foundation, the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) (R37AI095983 for JLC), and grants from the French National Research Agency (GENMSMD, ANR-16-CE17-0005-01 for JB, and ANR GENCMCD, ANR-11-BSV3-005-01 for AP).
Publisher Copyright:
© Copyright © 2021 Taur, Gowri, Pandrowala, Iyengar, Chougule, Golwala, Chandak, Agarwal, Keni, Dighe, Bodhanwala, Prabhu, George, Fouzia, Edison, Arunachalam, Madkaikar, Dalvi, Yadav, Bargir, Kambli, Rawat, Das, Joshi, Pilania, Jindal, Bhat, Bhattad, Unni, Radhakrishnan, Raj, Uppuluri, Patel, Lashkari, Aggarwal, Kalra, Udwadia, Bafna, Kanade, Puel, Bustamante, Casanova and Desai.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2/25
Y1 - 2021/2/25
N2 - Mendelian Susceptibility to Mycobacterial diseases (MSMD) are a group of innate immune defects with more than 17 genes and 32 clinical phenotypes identified. Defects in the IFN-γ mediated immunity lead to an increased susceptibility to intracellular pathogens like mycobacteria including attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains and non-tuberculous environmental mycobacteria (NTM), Salmonella, fungi, parasites like Leishmania and some viruses, in otherwise healthy individuals. Mutations in the IL12RB1 gene are the commonest genetic defects identified. This retrospective study reports the clinical, immunological, and molecular characteristics of a cohort of 55 MSMD patients from 10 centers across India. Mycobacterial infection was confirmed by GeneXpert, Histopathology, and acid fast bacilli staining. Immunological workup included lymphocyte subset analysis, Nitro blue tetrazolium (NBT) test, immunoglobulin levels, and flow-cytometric evaluation of the IFN-γ mediated immunity. Genetic analysis was done by next generation sequencing (NGS). Disseminated BCG-osis was the commonest presenting manifestation (82%) with a median age of presentation of 6 months due to the practice of BCG vaccination at birth. This was followed by infection with Salmonella and non-typhi Salmonella (13%), Cytomegalovirus (CMV) (11%), Candida (7%), NTM (4%), and Histoplasma (2%). Thirty-six percent of patients in cohort were infected by more than one organism. This study is the largest cohort of MSMD patients reported from India to the best of our knowledge and we highlight the importance of work up for IL-12/IL-23/ISG15/IFN-γ circuit in all patients with BCG-osis and suspected MSMD irrespective of age.
AB - Mendelian Susceptibility to Mycobacterial diseases (MSMD) are a group of innate immune defects with more than 17 genes and 32 clinical phenotypes identified. Defects in the IFN-γ mediated immunity lead to an increased susceptibility to intracellular pathogens like mycobacteria including attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains and non-tuberculous environmental mycobacteria (NTM), Salmonella, fungi, parasites like Leishmania and some viruses, in otherwise healthy individuals. Mutations in the IL12RB1 gene are the commonest genetic defects identified. This retrospective study reports the clinical, immunological, and molecular characteristics of a cohort of 55 MSMD patients from 10 centers across India. Mycobacterial infection was confirmed by GeneXpert, Histopathology, and acid fast bacilli staining. Immunological workup included lymphocyte subset analysis, Nitro blue tetrazolium (NBT) test, immunoglobulin levels, and flow-cytometric evaluation of the IFN-γ mediated immunity. Genetic analysis was done by next generation sequencing (NGS). Disseminated BCG-osis was the commonest presenting manifestation (82%) with a median age of presentation of 6 months due to the practice of BCG vaccination at birth. This was followed by infection with Salmonella and non-typhi Salmonella (13%), Cytomegalovirus (CMV) (11%), Candida (7%), NTM (4%), and Histoplasma (2%). Thirty-six percent of patients in cohort were infected by more than one organism. This study is the largest cohort of MSMD patients reported from India to the best of our knowledge and we highlight the importance of work up for IL-12/IL-23/ISG15/IFN-γ circuit in all patients with BCG-osis and suspected MSMD irrespective of age.
UR - http://www.scopus.com/inward/record.url?scp=85102477696&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102477696&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.631298
DO - 10.3389/fimmu.2021.631298
M3 - Article
AN - SCOPUS:85102477696
SN - 1664-3224
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 631298
ER -
