Mendelian susceptibility to mycobacterial disease: Clinical, immunological, and genetic study in India
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare syndrome characterized by increased and selective susceptibility to weakly virulent mycobacteria and other intramacrophagic pathogens. This study emphasizes the utility of immunological and functional assays in diagnosing MSMD by analyzing clinical, immunological, and genetic features in 50 Indian patients. Immunological workup included lymphocyte subset analysis, nitroblue tetrazolium test (NBT), and flow cytometric assessment of IFN-γR1 (CD119), IL-12Rβ1 (CD212), and phosphorylated STAT1/STAT4 following cytokine stimulation. Functional assays measured IFN-γ and IL-12p70 production. Genetic evaluation was performed using whole-exome or Sanger sequencing. The median age at onset was 3 mo. BCG complications were the most common presentation (96%), while 4% had non-tuberculous mycobacterial infections. Additional infections included Mycobacterium tuberculosis, Salmonella spp., Candida spp., and multiple types of viruses. IL-12Rβ1 deficiency was the most frequent diagnosis, with 10 novel variants in the IL12RB1 gene identified. These results demonstrate that combining flow cytometry with functional and genetic analyses enables accurate and timely MSMD diagnosis.
Authors
- Priyanka Kambli (ORCID: https://orcid.org/0000-0001-5713-9482)
- Jahnavi Aluri (ORCID: https://orcid.org/0000-0002-0350-1439)
- Parag Mohan Tamhankar (ORCID: https://orcid.org/0000-0003-3584-2382)
- Aparna Dhondi Dalvi (ORCID: https://orcid.org/0009-0007-6972-6474)
- Swati Garg (ORCID: https://orcid.org/0000-0002-3719-4342)
- Priyanka Setia (ORCID: https://orcid.org/0000-0003-0985-0303)
- Harsha Prasada Lashkari (ORCID: https://orcid.org/0000-0002-6398-6546)
- Manisha Rajan Madkaikar (ORCID: https://orcid.org/0000-0001-6380-3116)
- Shweta Shinde (ORCID: https://orcid.org/0009-0003-7012-7605)
- Shraddha Shelar (ORCID: https://orcid.org/0009-0001-1475-3770)
- Jean‐Laurent Casanova (ORCID: https://orcid.org/0000-0002-7782-4169)
- Gouri Hule (ORCID: https://orcid.org/0000-0003-0558-743X)
- Umair Ahmed Bargir (ORCID: https://orcid.org/0000-0001-6785-8042)
- Asruti Kacha (ORCID: https://orcid.org/0009-0000-4636-9469)
- Reetika Malik Yadav (ORCID: https://orcid.org/0000-0002-5030-0437)
- Meena Sivasankaran (ORCID: https://orcid.org/0000-0001-5759-125X)
- Amruta Dhawale (ORCID: https://orcid.org/0000-0002-8755-9426)
- Jacinta Bustamante (ORCID: https://orcid.org/0000-0002-3439-2482)
- Neha Jodhawat (ORCID: https://orcid.org/0000-0002-7752-3956)
- Swati Kanakia (ORCID: https://orcid.org/0009-0002-1424-5634)
- Sagar Bhattad (ORCID: https://orcid.org/0000-0002-5048-9727)
- Mukesh Desai (ORCID: https://orcid.org/0000-0002-9253-7934)
- T. Usha Bharathi (ORCID: https://orcid.org/0000-0001-7526-9571)
- K Gandhi (ORCID: https://orcid.org/0009-0005-6105-9190)
- Lavina Temkar (ORCID: https://orcid.org/0000-0002-3448-5638)
- Ramesh Kawale (ORCID: https://orcid.org/0009-0004-1049-4638)
- Nitin Salve (ORCID: https://orcid.org/0009-0002-6269-2869)
Institutions
- Inserm (FR)
- Manipal Academy of Higher Education (IN)
- Université Paris Cité (FR)
- Lilavati Hospital & Research Centre (IN)
- Sorbonne Paris Cité (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Government Medical College (IN)
- ICMR - National Institute of Immunohaemotology (IN)
- Bai Jerbai Wadia Hospital for Children (IN)
- Research Centre for Medical Genetics (RU)
- Kanchi Kamakoti CHILDS Trust Hospital (IN)
- Human Genetic of Infectious Diseases (FR)
- Institut des Maladies Génétiques Imagine (FR)
- Pediatric Infectious Diseases Society (US)
- Immune Deficiency Foundation (US)
- Kurnool Medical College (IN)
- Kasturba Medical College, Manipal (IN)
- Rockefeller University (US)
Publication Details
- Journal
- Journal of Human Immunity
- Published
- 2025-11-11
- DOI
- https://doi.org/10.70962/jhi.20250153
- Primary Topic
- Mycobacterium research and diagnosis
- Type
- article
- Field-Weighted Citation Impact
- 0.00