Familial hemophagocytic lymphohistiocytosis: too little cell death can seriously damage your health.
Leuk Lymphoma
; 42(1-2): 13-20, 2001 Jun.
Article
em En
| MEDLINE
| ID: mdl-11699200
ABSTRACT
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare and fatal disease of early childhood characterized by a non-malignant accumulation of activated T lymphocytes and histiocytes in the reticuloendothelial system. Moreover, immune system derangement, with prominent hypercytokinemia and low or absent cytotoxic T and natural killer (NK) cell activity, is a consistent feature of this autosomal recessive disorder. Recent work has demonstrated that the degree of spontaneous caspase activation in FHL lymphocytes is attenuated in vitro whereas Fas-mediated caspase activation and apoptosis induction remains unmitigated, and FHL can thus be distinguished from the related chronic disorder of immune regulation termed autoimmune lymphoproliferative syndrome or ALPS. However, subsequent studies have identified mutations in the gene encoding perforin, a cytotoxic granule constituent required for apoptotic killing of target cells, in a number of FHL patients. Hence, the underlying defect in FHL may be conceived of as a lack of apoptosis triggering within the immune system, rather than apoptosis resistance per se. These observations represent an important step in our understanding of the pathogenesis of FHL and also serve to emphasize the pivotal role of cellular (perforin-based) cytotoxicity in the regulation of immune homeostasis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Histiocitose de Células não Langerhans
Limite:
Animals
/
Child
/
Child, preschool
/
Humans
Idioma:
En
Revista:
Leuk Lymphoma
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Suécia