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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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