Publication Date:
1999-12-03
Description:
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, rapidly fatal, autosomal recessive immune disorder characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines. Linkage analyses indicate that FHL is genetically heterogeneous and linked to 9q21.3-22, 10q21-22, or another as yet undefined locus. Sequencing of the coding regions of the perforin gene of eight unrelated 10q21-22-linked FHL patients revealed homozygous nonsense mutations in four patients and missense mutations in the other four patients. Cultured lymphocytes from patients had defective cytotoxic activity, and immunostaining revealed little or no perforin in the granules. Thus, defects in perforin are responsible for 10q21-22-linked FHL. Perforin-based effector systems are, therefore, involved not only in the lysis of abnormal cells but also in the down-regulation of cellular immune activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stepp, S E -- Dufourcq-Lagelouse, R -- Le Deist, F -- Bhawan, S -- Certain, S -- Mathew, P A -- Henter, J I -- Bennett, M -- Fischer, A -- de Saint Basile, G -- Kumar, V -- New York, N.Y. -- Science. 1999 Dec 3;286(5446):1957-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and the Graduate Program in Immunology, University of Texas Southwestern Medical School, Dallas, TX 75235, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10583959" target="_blank"〉PubMed〈/a〉
Keywords:
Antigen-Presenting Cells/immunology
;
Cell Death
;
Cell Line
;
Cells, Cultured
;
Chromosome Mapping
;
Chromosomes, Human, Pair 10/*genetics
;
Codon, Terminator
;
Cytoplasmic Granules/chemistry
;
Cytotoxicity, Immunologic
;
Frameshift Mutation
;
Genetic Linkage
;
Granzymes
;
Heterozygote
;
Histiocytosis, Non-Langerhans-Cell/*genetics/immunology
;
Humans
;
Lymphocyte Activation
;
Membrane Glycoproteins/analysis/*genetics/physiology
;
Mutation, Missense
;
Perforin
;
Point Mutation
;
Pore Forming Cytotoxic Proteins
;
Serine Endopeptidases/analysis
;
T-Lymphocytes, Cytotoxic/chemistry/immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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