Monogenic defects in lymphocyte apoptosisFleisher, Thomas A.; Oliveira, Joao BoscoCurrent 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 Abstract Author Information 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: email@example.com Copyright © 2012 Wolters Kluwer Health, Inc. All rights reserved.