Monogenic defects in lymphocyte apoptosis.
OBJECTIVE
The recognition that apoptosis - programmed cell death - is an important mechanism in immune homeostasis has led to the identification of human disorders associated with defects in the critical control mechanism.


RESULTS
Patients have been identified with defects affecting the extrinsic apoptotic pathway mediated by the protein receptor FAS which results in the autoimmune lymphoproliferative syndrome and more recently in defects affecting the intrinsic apoptotic pathway mediated by RAS proteins resulting in the RAS-associated autoimmune leukoproliferative disorder. This review summarizes the immunopathogenesis, clinical features and diagnostic approaches to these human disorders.


CONCLUSIONS
Apoptotic pathways are critical in the maintenance of leukocyte homeostasis, and genetic defects impacting these can result in clinical disease manifested as expansion of selected leukocyte populations, autoimmunity, increased risk for malignancy and in some situations defects in host defense.
NIH Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1508, USA. tfleishe@mail.nih.gov
Thomas A
TA
Fleisher
Joao Bosco
JB
Oliveira
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D056735:Autoimmune Lymphoproliferative Syndrome / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000097:blood; D019014:fas Receptor / Q000235:genetics / Q000276:immunology; D018631:ras Proteins / Q000235:genetics / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta; D019014:fas Receptor; D018631:ras Proteins