Document Detail

Biology and treatment of familial hemophagocytic lymphohistiocytosis: importance of perforin in lymphocyte-mediated cytotoxicity and triggering of apoptosis.
MedLine Citation:
PMID:  11979453     Owner:  NLM     Status:  MEDLINE    
Familial hemophagocytic lymphohistiocytosis (FHL) is, without treatment, an invariably fatal disease of infancy and early childhood characterized by fever, hepatosplenomegaly, pancytopenia, and a widespread accumulation of T-lymphocytes and macrophages. During recent years, the diagnosis and the survival as well as the understanding of the disease have improved dramatically. Recent studies suggest that FHL is caused by impaired lymphocyte-mediated cytotoxicity and defective triggering of apoptosis, and that the symptoms are mediated by a pro-inflammatory hypercytokinemia. Moreover, specific genetic alterations, mutations in the perforin gene, have been revealed in FHL patients. Perforin, which normally is secreted from cytotoxic T-lymphocytes and natural killer (NK) cells upon conjugation between effector and target cells, is able to insert into the membrane of the target cell. It there polymerizes to form a cell death-inducing pore through which toxic granzymes may enter the cell and trigger apoptosis. The establishment of perforin deficiency as a cause of the rapidly fatal disease FHL has demonstrated the essential role of perforin in human immune homeostasis.
Jan-Inge Henter
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Medical and pediatric oncology     Volume:  38     ISSN:  0098-1532     ISO Abbreviation:  Med. Pediatr. Oncol.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-05-23     Completed Date:  2002-06-04     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7506654     Medline TA:  Med Pediatr Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  305-9     Citation Subset:  IM    
Copyright Information:
Copyright 2002 Wiley-Liss, Inc.
Childhood Cancer Research Unit, Karolinska Institute, Department of Pediatric Hematology and Oncology, Astrid Lindgren Children's Hospital, Karolinska Hospital, Stockholm, Sweden.
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MeSH Terms
Apoptosis / physiology*
Child, Preschool
Diagnosis, Differential
Histiocytosis, Non-Langerhans-Cell / genetics*,  physiopathology*
Infant, Newborn
Killer Cells, Natural / physiology
Membrane Glycoproteins / deficiency*,  pharmacology*
Pore Forming Cytotoxic Proteins
T-Lymphocytes, Cytotoxic / physiology*
Reg. No./Substance:
0/Membrane Glycoproteins; 0/Pore Forming Cytotoxic Proteins; 126465-35-8/Perforin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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