Familial hemophagocytic lymphohistiocytosis: too little cell death can seriously damage your health.

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.

journal_name

Leuk Lymphoma

journal_title

Leukemia & lymphoma

authors

Fadeel B,Orrenius S,Henter JI

doi

10.3109/10428190109097672

keywords:

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

13-20

issue

1-2

eissn

1042-8194

issn

1029-2403

journal_volume

42

pub_type

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