AUTHOR=Taur Prasad D. , Gowri Vijaya , Pandrowala Ambreen Abdulwahab , Iyengar Vaishnavi V. , Chougule Akshaya , Golwala Zainab , Chandak Shraddha , Agarwal Reepa , Keni Purva , Dighe Neha , Bodhanwala Minnie , Prabhu Shakuntala , George Biju , Fouzia N. A. , Edison Eunice Sindhuvi , Arunachalam Arun Kumar , Madkaikar Manisha Rajan , Dalvi Aparna Dhondi , Yadav Reetika Malik , Bargir Umair Ahmed , Kambli Priyanka Madhav , Rawat Amit , Das Jhumki , Joshi Vibhu , Pilania Rakesh Kumar , Jindal Ankur Kumar , Bhat Sunil , Bhattad Sagar , Unni Jeeson , Radhakrishnan Nita , Raj Revathi , Uppuluri Ramya , Patel Shivani , Lashkari Harsha Prasada , Aggarwal Amita , Kalra Manas , Udwadia Zarir , Bafna Vibha Sanjay , Kanade Tarun , Puel Anne , Bustamante Jacinta , Casanova Jean Laurent , Desai Mukesh M. TITLE=Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.631298 DOI=10.3389/fimmu.2021.631298 ISSN=1664-3224 ABSTRACT=

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.