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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.
Afiliación
  • Shabrish S; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Kelkar M; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Yadav RM; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Bargir UA; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Gupta M; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Dalvi A; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Aluri J; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Kulkarni M; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Shinde S; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Sawant-Desai S; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Kambli P; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Hule G; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Setia P; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Jodhawat N; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Gaikwad P; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Dhawale A; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Nambiar N; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
  • Gowri V; Department of Immunology, Bai Jerbai Wadia Hospital for Children, Mumbai, India.
  • Pandrowala A; Department of Bone Marrow Transplant, Bai Jerbai Wadia Hospital for Children, Mumbai, India.
  • Taur P; Department of Immunology, Bai Jerbai Wadia Hospital for Children, Mumbai, India.
  • Raj R; Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Apollo Hospitals, Chennai, India.
  • Uppuluri R; Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Apollo Hospitals, Chennai, India.
  • Sharma R; Comprehensive Thalassemia Care, Pediatric Hematology-Oncology & Bone Marrow Transplantation Centre, Mumbai, India.
  • Kini P; Comprehensive Thalassemia Care, Pediatric Hematology-Oncology & Bone Marrow Transplantation Centre, Mumbai, India.
  • Sivasankaran M; Department of Pediatric Hemato-Oncology, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India.
  • Munirathnam D; Department of Pediatric Hemato-Oncology, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India.
  • Vedam R; Medgenome Labs Pvt Ltd., Narayana Health City, Bommasandra, India.
  • Vignesh P; Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
  • Banday A; Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
  • Rawat A; Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
  • Aggarwal A; Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
  • Poddar U; Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
  • Girish M; Department of Pediatrics, All India Institute of Medical Sciences, Nagpur, India.
  • Chaudhary A; Department of Pediatrics, All India Institute of Medical Sciences, Nagpur, India.
  • Sampagar A; KAHER'S Jawaharlal Nehru Medical College, Belagavi, India.
  • Jayaraman D; Department of Pediatrics, Sri Ramchandra Institute of Higher Education and Research, Chennai, India.
  • Chaudhary N; Department of Pediatrics, All India Institute of Medical Sciences, Bhopal, India.
  • Shah N; P.D. Hinduja Hospital, Mumbai, India.
  • Jijina F; P.D. Hinduja Hospital, Mumbai, India.
  • Chandrakla S; Department of Haematology, Seth G. S. Medical College and King Edward Memorial Hospital, Mumbai, India.
  • Kanakia S; Lilavati Hospital and Research Centre, Mumbai, India.
  • Arora B; Department of Pediatric Oncology, Tata Memorial Hospital, Mumbai, India.
  • Sen S; Kokilaben Dhirubai Ambani Hospital, Mumbai, India.
  • Lokeshwar M; Kashyap Nursing Home, Mumbai, India.
  • Desai M; Department of Immunology, Bai Jerbai Wadia Hospital for Children, Mumbai, India.
  • Madkaikar M; Department of Pediatric Immunology and Leukocyte Biology, Indian Council of Medical Research-National Institute of Immunohaematology, Mumbai, India.
Front Immunol ; 12: 612583, 2021.
Article en En | MEDLINE | ID: mdl-33746956
ABSTRACT
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Biomarcadores / Susceptibilidad a Enfermedades / Linfohistiocitosis Hemofagocítica Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Child / Child, preschool / Female / Humans / Infant / Male País/Región como asunto: Asia Idioma: En Revista: Front Immunol Año: 2021 Tipo del documento: Article País de afiliación: India

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Biomarcadores / Susceptibilidad a Enfermedades / Linfohistiocitosis Hemofagocítica Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Child / Child, preschool / Female / Humans / Infant / Male País/Región como asunto: Asia Idioma: En Revista: Front Immunol Año: 2021 Tipo del documento: Article País de afiliación: India