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The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of immune dysregulation characterized by hyperactivation of the immune system, excessive cytokine secretion and severe systemic inflammation. HLH is classified as familial (FHL) when associated with mutations in PRF1, UNC13D, STX11, and STXBP2 g...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973116/ https://www.ncbi.nlm.nih.gov/pubmed/33746956 http://dx.doi.org/10.3389/fimmu.2021.612583 |
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author | Shabrish, Snehal Kelkar, Madhura Yadav, Reetika Malik Bargir, Umair Ahmed Gupta, Maya Dalvi, Aparna Aluri, Jahnavi Kulkarni, Manasi Shinde, Shweta Sawant-Desai, Sneha Kambli, Priyanka Hule, Gouri Setia, Priyanka Jodhawat, Neha Gaikwad, Pallavi Dhawale, Amruta Nambiar, Nayana Gowri, Vijaya Pandrowala, Ambreen Taur, Prasad Raj, Revathi Uppuluri, Ramya Sharma, Ratna Kini, Pranoti Sivasankaran, Meena Munirathnam, Deenadayalan Vedam, Ramprasad Vignesh, Pandiarajan Banday, Aaqib Rawat, Amit Aggarwal, Amita Poddar, Ujjal Girish, Meenakshi Chaudhary, Abhijit Sampagar, Abhilasha Jayaraman, Dharani Chaudhary, Narendra Shah, Nitin Jijina, Farah Chandrakla, S. Kanakia, Swati Arora, Brijesh Sen, Santanu Lokeshwar, Madhukar Desai, Mukesh Madkaikar, Manisha |
author_facet | Shabrish, Snehal Kelkar, Madhura Yadav, Reetika Malik Bargir, Umair Ahmed Gupta, Maya Dalvi, Aparna Aluri, Jahnavi Kulkarni, Manasi Shinde, Shweta Sawant-Desai, Sneha Kambli, Priyanka Hule, Gouri Setia, Priyanka Jodhawat, Neha Gaikwad, Pallavi Dhawale, Amruta Nambiar, Nayana Gowri, Vijaya Pandrowala, Ambreen Taur, Prasad Raj, Revathi Uppuluri, Ramya Sharma, Ratna Kini, Pranoti Sivasankaran, Meena Munirathnam, Deenadayalan Vedam, Ramprasad Vignesh, Pandiarajan Banday, Aaqib Rawat, Amit Aggarwal, Amita Poddar, Ujjal Girish, Meenakshi Chaudhary, Abhijit Sampagar, Abhilasha Jayaraman, Dharani Chaudhary, Narendra Shah, Nitin Jijina, Farah Chandrakla, S. Kanakia, Swati Arora, Brijesh Sen, Santanu Lokeshwar, Madhukar Desai, Mukesh Madkaikar, Manisha |
author_sort | Shabrish, Snehal |
collection | PubMed |
description | Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of immune dysregulation characterized by hyperactivation of the immune system, excessive cytokine secretion and severe systemic inflammation. HLH is classified as familial (FHL) when associated with mutations in PRF1, UNC13D, STX11, and STXBP2 genes. There is limited information available about the clinical and mutational spectrum of FHL patients in Indian population. This study is a retrospective analysis of 101 molecularly characterized FHL patients over the last 10 years from 20 different referral centers in India. FHL2 and FHL3 together accounted for 84% of cases of FHL in our cohort. Patients belonging to different FHL subtypes were indistinguishable based on clinical and biochemical parameters. However, flow cytometry-based assays viz. perforin expression and degranulation assay were found to be specific and sensitive in diagnosis and classification of FHL patients. Molecular characterization of respective genes revealed 76 different disease-causing mutations including 39 (51%) novel mutations in PRF1, UNC13D, STX11, and STXBP2 genes. Overall, survival was poor (28%) irrespective of the age of onset or the type of mutation in our cohort. Altogether, this article sheds light on the current scenario of FHL in India. Our data reveal a wide genetic heterogeneity of FHL in the Indian population and confirms the poor prognosis of FHL. This study also emphasizes that though mutational analysis is important for diagnostic confirmation of FHL, flow cytometry based assays help significantly in rapid diagnosis and functional validation of novel variants identified. |
format | Online Article Text |
id | pubmed-7973116 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79731162021-03-20 The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India Shabrish, Snehal Kelkar, Madhura Yadav, Reetika Malik Bargir, Umair Ahmed Gupta, Maya Dalvi, Aparna Aluri, Jahnavi Kulkarni, Manasi Shinde, Shweta Sawant-Desai, Sneha Kambli, Priyanka Hule, Gouri Setia, Priyanka Jodhawat, Neha Gaikwad, Pallavi Dhawale, Amruta Nambiar, Nayana Gowri, Vijaya Pandrowala, Ambreen Taur, Prasad Raj, Revathi Uppuluri, Ramya Sharma, Ratna Kini, Pranoti Sivasankaran, Meena Munirathnam, Deenadayalan Vedam, Ramprasad Vignesh, Pandiarajan Banday, Aaqib Rawat, Amit Aggarwal, Amita Poddar, Ujjal Girish, Meenakshi Chaudhary, Abhijit Sampagar, Abhilasha Jayaraman, Dharani Chaudhary, Narendra Shah, Nitin Jijina, Farah Chandrakla, S. Kanakia, Swati Arora, Brijesh Sen, Santanu Lokeshwar, Madhukar Desai, Mukesh Madkaikar, Manisha Front Immunol Immunology Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of immune dysregulation characterized by hyperactivation of the immune system, excessive cytokine secretion and severe systemic inflammation. HLH is classified as familial (FHL) when associated with mutations in PRF1, UNC13D, STX11, and STXBP2 genes. There is limited information available about the clinical and mutational spectrum of FHL patients in Indian population. This study is a retrospective analysis of 101 molecularly characterized FHL patients over the last 10 years from 20 different referral centers in India. FHL2 and FHL3 together accounted for 84% of cases of FHL in our cohort. Patients belonging to different FHL subtypes were indistinguishable based on clinical and biochemical parameters. However, flow cytometry-based assays viz. perforin expression and degranulation assay were found to be specific and sensitive in diagnosis and classification of FHL patients. Molecular characterization of respective genes revealed 76 different disease-causing mutations including 39 (51%) novel mutations in PRF1, UNC13D, STX11, and STXBP2 genes. Overall, survival was poor (28%) irrespective of the age of onset or the type of mutation in our cohort. Altogether, this article sheds light on the current scenario of FHL in India. Our data reveal a wide genetic heterogeneity of FHL in the Indian population and confirms the poor prognosis of FHL. This study also emphasizes that though mutational analysis is important for diagnostic confirmation of FHL, flow cytometry based assays help significantly in rapid diagnosis and functional validation of novel variants identified. Frontiers Media S.A. 2021-03-05 /pmc/articles/PMC7973116/ /pubmed/33746956 http://dx.doi.org/10.3389/fimmu.2021.612583 Text en Copyright © 2021 Shabrish, Kelkar, Yadav, Bargir, Gupta, Dalvi, Aluri, Kulkarni, Shinde, Sawant-Desai, Kambli, Hule, Setia, Jodhawat, Gaikwad, Dhawale, Nambiar, Gowri, Pandrowala, Taur, Raj, Uppuluri, Sharma, Kini, Sivasankaran, Munirathnam, Vedam, Vignesh, Banday, Rawat, Aggarwal, Poddar, Girish, Chaudhary, Sampagar, Jayaraman, Chaudhary, Shah, Jijina, Chandrakla, Kanakia, Arora, Sen, Lokeshwar, Desai and Madkaikar. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Shabrish, Snehal Kelkar, Madhura Yadav, Reetika Malik Bargir, Umair Ahmed Gupta, Maya Dalvi, Aparna Aluri, Jahnavi Kulkarni, Manasi Shinde, Shweta Sawant-Desai, Sneha Kambli, Priyanka Hule, Gouri Setia, Priyanka Jodhawat, Neha Gaikwad, Pallavi Dhawale, Amruta Nambiar, Nayana Gowri, Vijaya Pandrowala, Ambreen Taur, Prasad Raj, Revathi Uppuluri, Ramya Sharma, Ratna Kini, Pranoti Sivasankaran, Meena Munirathnam, Deenadayalan Vedam, Ramprasad Vignesh, Pandiarajan Banday, Aaqib Rawat, Amit Aggarwal, Amita Poddar, Ujjal Girish, Meenakshi Chaudhary, Abhijit Sampagar, Abhilasha Jayaraman, Dharani Chaudhary, Narendra Shah, Nitin Jijina, Farah Chandrakla, S. Kanakia, Swati Arora, Brijesh Sen, Santanu Lokeshwar, Madhukar Desai, Mukesh Madkaikar, Manisha The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India |
title | The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India |
title_full | The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India |
title_fullStr | The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India |
title_full_unstemmed | The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India |
title_short | The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India |
title_sort | spectrum of clinical, immunological, and molecular findings in familial hemophagocytic lymphohistiocytosis: experience from india |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973116/ https://www.ncbi.nlm.nih.gov/pubmed/33746956 http://dx.doi.org/10.3389/fimmu.2021.612583 |
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