NDLI: A Rapid Ex Vivo Clinical Diagnostic Assay for Fas Receptor-Induced T Lymphocyte Apoptosis

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A Rapid Ex Vivo Clinical Diagnostic Assay for Fas Receptor-Induced T Lymphocyte Apoptosis

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A Rapid Ex Vivo Clinical Diagnostic Assay for Fas Receptor-Induced T Lymphocyte Apoptosis

Content Provider	Springer Nature Link
Author	Lo, Bernice Ramaswamy, Madhu Davis, Joie Price, Susan Rao, V. Koneti Siegel, Richard M. Lenardo, Michael J.
Copyright Year	2012
Abstract	Deleterious mutations in genes involved in the Fas apoptosis pathway lead to Autoimmune Lymphoproliferative Syndrome (ALPS). Demonstration of an apoptosis defect is critical for the diagnosis and study of ALPS. The traditional in vitro apoptosis assay, however, requires a week of experimental procedures. Here, we show that defects in Fas-induced apoptosis in PBMCs can be evaluated directly ex vivo using multicolor flow cytometry to analyze the apoptosis of effector memory T cells, a Fas-sensitive subset of PBMCs. This method allowed us to sensitively quantify defective apoptosis in ALPS patients within a few hours. Some ALPS patients (ALPS-sFAS) without germline mutations have somatic mutations in Fas specifically in double-negative αβ T cells (DNTs), an unusual lymphocyte population that is characteristically expanded in ALPS. Since DNTs have been notoriously difficult to culture, defective apoptosis has not been previously demonstrated for ALPS-sFAS patients. Using our novel ex vivo apoptosis assay, we measured Fas-induced apoptosis of DNTs for the first time and found that ALPS-sFAS patients had significant apoptosis defects in these cells compared to healthy controls. Hence, this rapid apoptosis assay can expedite the diagnosis of new ALPS patients, including those with somatic mutations, and facilitate clinical and molecular investigation of these diseases.
Starting Page	479
Ending Page	488
Page Count	10
File Format	PDF
ISSN	02719142
Journal	Journal of Clinical Immunology
Volume Number	33
Issue Number	2
e-ISSN	15732592
Language	English
Publisher	Springer US
Publisher Date	2012-10-11
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Apoptosis Fas Autoimmune Lymphoproliferative syndrome diagnosis effector memory T cells double-negative T cells Immunology Infectious Diseases Internal Medicine Medical Microbiology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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A rapid ex vivo clinical diagnostic assay for Fas receptor-induced T lymphocyte apoptosis

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A novel homozygous Fas ligand mutation leads to early protein truncation, abrogation of death receptor and reverse signaling and a severe form of the autoimmune lymphoproliferative syndrome.

A Rapid Ex Vivo Clinical Diagnostic Assay for Fas Receptor-Induced T Lymphocyte Apoptosis

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A rapid ex vivo clinical diagnostic assay for Fas receptor-induced T lymphocyte apoptosis

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A Rapid Ex Vivo Clinical Diagnostic Assay for Fas Receptor-Induced T Lymphocyte Apoptosis