Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India
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 M...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.631298/full |
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| author | Prasad D. Taur Vijaya Gowri Ambreen Abdulwahab Pandrowala Vaishnavi V. Iyengar Akshaya Chougule Zainab Golwala Shraddha Chandak Reepa Agarwal Purva Keni Neha Dighe Minnie Bodhanwala Shakuntala Prabhu Biju George N. A. Fouzia Eunice Sindhuvi Edison Arun Kumar Arunachalam Manisha Rajan Madkaikar Aparna Dhondi Dalvi Reetika Malik Yadav Umair Ahmed Bargir Priyanka Madhav Kambli Amit Rawat Jhumki Das Vibhu Joshi Rakesh Kumar Pilania Ankur Kumar Jindal Sunil Bhat Sagar Bhattad Jeeson Unni Nita Radhakrishnan Revathi Raj Ramya Uppuluri Shivani Patel Harsha Prasada Lashkari Amita Aggarwal Manas Kalra Zarir Udwadia Vibha Sanjay Bafna Tarun Kanade Anne Puel Anne Puel Anne Puel Jacinta Bustamante Jacinta Bustamante Jacinta Bustamante Jacinta Bustamante Jean Laurent Casanova Jean Laurent Casanova Jean Laurent Casanova Jean Laurent Casanova Mukesh M. Desai |
| author_facet | Prasad D. Taur Vijaya Gowri Ambreen Abdulwahab Pandrowala Vaishnavi V. Iyengar Akshaya Chougule Zainab Golwala Shraddha Chandak Reepa Agarwal Purva Keni Neha Dighe Minnie Bodhanwala Shakuntala Prabhu Biju George N. A. Fouzia Eunice Sindhuvi Edison Arun Kumar Arunachalam Manisha Rajan Madkaikar Aparna Dhondi Dalvi Reetika Malik Yadav Umair Ahmed Bargir Priyanka Madhav Kambli Amit Rawat Jhumki Das Vibhu Joshi Rakesh Kumar Pilania Ankur Kumar Jindal Sunil Bhat Sagar Bhattad Jeeson Unni Nita Radhakrishnan Revathi Raj Ramya Uppuluri Shivani Patel Harsha Prasada Lashkari Amita Aggarwal Manas Kalra Zarir Udwadia Vibha Sanjay Bafna Tarun Kanade Anne Puel Anne Puel Anne Puel Jacinta Bustamante Jacinta Bustamante Jacinta Bustamante Jacinta Bustamante Jean Laurent Casanova Jean Laurent Casanova Jean Laurent Casanova Jean Laurent Casanova Mukesh M. Desai |
| author_sort | Prasad D. Taur |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T16:50:41Z |
| format | Article |
| id | doaj.art-8a04c992f5fc4d16bb35320fd3aa42b4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T16:50:41Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8a04c992f5fc4d16bb35320fd3aa42b42022-12-21T22:24:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011210.3389/fimmu.2021.631298631298Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From IndiaPrasad D. Taur0Vijaya Gowri1Ambreen Abdulwahab Pandrowala2Vaishnavi V. Iyengar3Akshaya Chougule4Zainab Golwala5Shraddha Chandak6Reepa Agarwal7Purva Keni8Neha Dighe9Minnie Bodhanwala10Shakuntala Prabhu11Biju George12N. A. Fouzia13Eunice Sindhuvi Edison14Arun Kumar Arunachalam15Manisha Rajan Madkaikar16Aparna Dhondi Dalvi17Reetika Malik Yadav18Umair Ahmed Bargir19Priyanka Madhav Kambli20Amit Rawat21Jhumki Das22Vibhu Joshi23Rakesh Kumar Pilania24Ankur Kumar Jindal25Sunil Bhat26Sagar Bhattad27Jeeson Unni28Nita Radhakrishnan29Revathi Raj30Ramya Uppuluri31Shivani Patel32Harsha Prasada Lashkari33Amita Aggarwal34Manas Kalra35Zarir Udwadia36Vibha Sanjay Bafna37Tarun Kanade38Anne Puel39Anne Puel40Anne Puel41Jacinta Bustamante42Jacinta Bustamante43Jacinta Bustamante44Jacinta Bustamante45Jean Laurent Casanova46Jean Laurent Casanova47Jean Laurent Casanova48Jean Laurent Casanova49Mukesh M. Desai50Department of Immunology, B. J. Wadia Hospital for Children, Mumbai, IndiaDepartment of Immunology, B. J. Wadia Hospital for Children, Mumbai, IndiaDepartment of Immunology, B. J. Wadia Hospital for Children, Mumbai, IndiaDepartment of Immunology, B. J. Wadia Hospital for Children, Mumbai, IndiaDepartment of Immunology, B. J. Wadia Hospital for Children, Mumbai, IndiaDepartment of Immunology, B. J. Wadia Hospital for Children, Mumbai, IndiaDepartment of Immunology, B. J. Wadia Hospital for Children, Mumbai, IndiaDepartment of Immunology, B. J. Wadia Hospital for Children, Mumbai, IndiaDepartment of Immunology, B. J. Wadia Hospital for Children, Mumbai, IndiaDepartment of Immunology, B. J. Wadia Hospital for Children, Mumbai, IndiaDepartment of Immunology, B. J. Wadia Hospital for Children, Mumbai, IndiaDepartment of Immunology, B. J. Wadia Hospital for Children, Mumbai, IndiaDepartment of Clinical Hematology, Christian Medical College, Vellore, IndiaDepartment of Clinical Hematology, Christian Medical College, Vellore, IndiaDepartment of Clinical Hematology, Christian Medical College, Vellore, IndiaDepartment of Clinical Hematology, Christian Medical College, Vellore, IndiaIndian Council of Medical Research-National Institute of Immunohematology, Mumbai, IndiaIndian Council of Medical Research-National Institute of Immunohematology, Mumbai, IndiaIndian Council of Medical Research-National Institute of Immunohematology, Mumbai, IndiaIndian Council of Medical Research-National Institute of Immunohematology, Mumbai, IndiaIndian Council of Medical Research-National Institute of Immunohematology, Mumbai, IndiaDepartment of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, IndiaDepartment of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, IndiaDepartment of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, IndiaDepartment of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, IndiaDepartment of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, IndiaMazumdar Shaw Cancer Centre, Narayana Health City, Bengaluru, IndiaASTER CMI Hospitals, Bengaluru, IndiaASTER CMI Hospitals, Bengaluru, IndiaSuperspeciality Hospital, Noida, IndiaApollo Hospitals, Chennai, IndiaApollo Hospitals, Chennai, IndiaApollo Hospitals, Chennai, IndiaKasturba Medical College and Hospital, Mangalore, India0Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India1Sir Ganga Ram Hospital, New Delhi, India2Hinduja Hospital, Mumbai, India3Bharati Hospital, Pune, India4Rainbow Safalya Hospital, Nashik, India5University of Paris, Institute Imagine, INSERM, Paris, France6Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France7St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, United States5University of Paris, Institute Imagine, INSERM, Paris, France6Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France7St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, United States8Study Center for Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, Paris, France5University of Paris, Institute Imagine, INSERM, Paris, France6Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France7St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, United States9Howard Hughes Medical Institute, New York, NY, United StatesDepartment of Immunology, B. J. Wadia Hospital for Children, Mumbai, IndiaMendelian 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.631298/fullIL-12/IL-23/ISG15/IFN-γ axisintracellular pathogensBCG-osisMycobacterium tuberculosis complexIL-12Rβ1 defectanti-tubercular treatment |
| spellingShingle | Prasad D. Taur Vijaya Gowri Ambreen Abdulwahab Pandrowala Vaishnavi V. Iyengar Akshaya Chougule Zainab Golwala Shraddha Chandak Reepa Agarwal Purva Keni Neha Dighe Minnie Bodhanwala Shakuntala Prabhu Biju George N. A. Fouzia Eunice Sindhuvi Edison Arun Kumar Arunachalam Manisha Rajan Madkaikar Aparna Dhondi Dalvi Reetika Malik Yadav Umair Ahmed Bargir Priyanka Madhav Kambli Amit Rawat Jhumki Das Vibhu Joshi Rakesh Kumar Pilania Ankur Kumar Jindal Sunil Bhat Sagar Bhattad Jeeson Unni Nita Radhakrishnan Revathi Raj Ramya Uppuluri Shivani Patel Harsha Prasada Lashkari Amita Aggarwal Manas Kalra Zarir Udwadia Vibha Sanjay Bafna Tarun Kanade Anne Puel Anne Puel Anne Puel Jacinta Bustamante Jacinta Bustamante Jacinta Bustamante Jacinta Bustamante Jean Laurent Casanova Jean Laurent Casanova Jean Laurent Casanova Jean Laurent Casanova Mukesh M. Desai Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India Frontiers in Immunology IL-12/IL-23/ISG15/IFN-γ axis intracellular pathogens BCG-osis Mycobacterium tuberculosis complex IL-12Rβ1 defect anti-tubercular treatment |
| title | Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India |
| title_full | Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India |
| title_fullStr | Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India |
| title_full_unstemmed | Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India |
| title_short | Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India |
| title_sort | clinical and molecular findings in mendelian susceptibility to mycobacterial diseases experience from india |
| topic | IL-12/IL-23/ISG15/IFN-γ axis intracellular pathogens BCG-osis Mycobacterium tuberculosis complex IL-12Rβ1 defect anti-tubercular treatment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.631298/full |
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