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Monogenic defects in lymphocyte apoptosis

Fleisher, Thomas A.; Oliveira, Joao Bosco

Current Opinion in Allergy and Clinical Immunology: December 2012 - Volume 12 - Issue 6 - p 609–615
doi: 10.1097/ACI.0b013e3283588da0
PRIMARY IMMUNE DEFICIENCY DISEASE: Edited by Amos Etzioni and Ramsey L. Fuleihan

Purpose of review 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.

Recent findings 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.

Summary 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, USA

Correspondence to Thomas A. Fleisher, MD, Department of Laboratory Medicine, NIH Clinical Center, NIH, Building 10, Room 2C410, Bethesda, MD 20892-1508, USA. E-mail:

Copyright © 2012 Wolters Kluwer Health, Inc. All rights reserved.