The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India
| Autor: | Amruta Dhawale, Pallavi Gaikwad, Ramya Uppuluri, Snehal Shabrish, Swati Kanakia, Meena Sivasankaran, Ambreen Pandrowala, Dharani Jayaraman, Pranoti Kini, Abhilasha Sampagar, Deenadayalan Munirathnam, Sneha Sawant-Desai, Mukesh Desai, Aparna Dalvi, Shweta Shinde, Brijesh Arora, Pandiarajan Vignesh, Aaqib Zaffar Banday, Madhura Kelkar, Meenakshi Girish, Manisha Madkaikar, Jahnavi Aluri, Santanu Sen, Amit Rawat, Gouri Hule, Narendra K Chaudhary, Ramprasad Vedam, R Yadav, Nayana Nambiar, Umair Ahmed Bargir, Revathi Raj, Vijaya Gowri, Farah Jijina, Priyanka Setia, Neha Jodhawat, Manasi Kulkarni, M. R. Lokeshwar, Abhijit Chaudhary, S. Chandrakla, Priyanka Kambli, Ratna Sharma, Nitin Shah, Prasad Taur, Maya Gupta, Ujjal Poddar, Amita Aggarwal |
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| Rok vydání: | 2021 |
| Předmět: |
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lcsh:Immunologic diseases. Allergy Immunology India medicine.disease_cause Lymphohistiocytosis Hemophagocytic familial hemophagocytic lymphohistocytosis T-Lymphocyte Subsets Databases Genetic medicine Humans Immunology and Allergy Genetic Predisposition to Disease UNC13D HLH-targeted therapy Child flow cytomertry Alleles perforin Original Research degranulation Hemophagocytic lymphohistiocytosis biology Genetic heterogeneity business.industry Computational Biology Disease Management Infant Familial Hemophagocytic Lymphohistiocytosis Immune dysregulation medicine.disease Combined Modality Therapy Phenotype Treatment Outcome Perforin STX11 Child Preschool NGS Mutation biology.protein Female Cytokine secretion Disease Susceptibility lcsh:RC581-607 business Biomarkers |
| Zdroj: | Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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