Document Detail

A rapid ex vivo clinical diagnostic assay for fas receptor-induced T lymphocyte apoptosis.
MedLine Citation:
PMID:  23054345     Owner:  NLM     Status:  MEDLINE    
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.
Bernice Lo; Madhu Ramaswamy; Joie Davis; Susan Price; V Koneti Rao; Richard M Siegel; Michael J Lenardo
Related Documents :
21801845 - The transcriptional response of saccharomyces cerevisiae to proapoptotic concentrations...
8048225 - Cytokines and reproduction.
12687145 - Immunotherapy and immunorehabilitation in clinic of internal diseases.
9283955 - The effects of gonadotropin-releasing hormone immunization and recombinant follicle-sti...
21536105 - Lps elicits a much larger and broader inflammatory response than escherichia coli infec...
8608165 - Increased p53 mrna expression in liver and kidney apoptosis.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2012-10-11
Journal Detail:
Title:  Journal of clinical immunology     Volume:  33     ISSN:  1573-2592     ISO Abbreviation:  J. Clin. Immunol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-18     Completed Date:  2013-08-02     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  8102137     Medline TA:  J Clin Immunol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  479-88     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Aged, 80 and over
Antigens, CD95 / genetics,  metabolism*
Apoptosis* / immunology
Autoimmune Lymphoproliferative Syndrome / diagnosis*,  genetics,  immunology
Child, Preschool
Cytotoxicity Tests, Immunologic / methods*
Flow Cytometry
Middle Aged
Reproducibility of Results
Sensitivity and Specificity
T-Lymphocytes / immunology,  metabolism*
Young Adult
Grant Support
Reg. No./Substance:
0/Antigens, CD95

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Expression of IL-27, Th1 and Th17 in Patients with Aplastic Anemia.
Next Document:  Primary Immunodeficiency Diseases in Children: 15 Year Experience in a Tertiary Care Medical Center ...