FAS-L, IL-10, and double-negative CD4- CD8- TCR alpha/beta+ T cells are reliable markers of autoimmune lymphoproliferative syndrome (ALPS) associated with FAS loss of function

Aude Magerus-Chatinet; Marie-Claude Stolzenberg; Maria S Loffredo; Bénédicte Neven; Catherine Schaffner; Nicolas Ducrot; Peter D Arkwright; Brigitte Bader-Meunier; José Barbot; Stéphane Blanche; Jean-Laurent Casanova; Marianne Debré; Alina Ferster; Claire Fieschi; Benoit Florkin; Claire Galambrun; Olivier Hermine; Olivier Lambotte; Eric Solary; Caroline Thomas; Francoise Le Deist; Capucine Picard; Alain Fischer; Frédéric Rieux-Laucat

doi:10.1182/blood-2008-09-179630

FAS-L, IL-10, and double-negative CD4- CD8- TCR alpha/beta+ T cells are reliable markers of autoimmune lymphoproliferative syndrome (ALPS) associated with FAS loss of function

Blood. 2009 Mar 26;113(13):3027-30. doi: 10.1182/blood-2008-09-179630. Epub 2009 Jan 27.

Affiliation

¹ Inserm U768, Paris, France.

PMID: 19176318
DOI: 10.1182/blood-2008-09-179630

Abstract

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by splenomegaly, lymphadenopathy, hypergammaglobulinemia, accumulation of double-negative TCRalphabeta(+) CD4(-)CD8(-) T cells (DNT cells), and autoimmunity. Previously, DNT cell detection and a functional defect of T cells in a FAS-induced apoptosis test in vitro had been used for ALPS diagnosis. However, a functional defect can also be detected in mutation-positive relatives (MPRs) who remain free of any ALPS-related disease. In contrast, lymphocytes from patients carrying a somatic mutation of FAS exhibit normal sensitivity to FAS-induced apoptosis in vitro. We assessed the soluble FAS-L concentration in the plasma of ALPS patients carrying FAS mutations. Overall, we showed that determination of the FAS-L represents, together with the IL-10 concentration and the DNT cell percentage, a reliable tool for the diagnosis of ALPS.

Publication types

Evaluation Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Autoimmune Diseases / blood
Autoimmune Diseases / diagnosis*
Autoimmune Diseases / genetics
Autoimmune Diseases / metabolism
Biomarkers / blood
Biomarkers / metabolism
CD4 Antigens / blood
CD4 Antigens / metabolism
CD8 Antigens / blood
CD8 Antigens / metabolism
Case-Control Studies
Child
Child, Preschool
Fas Ligand Protein / blood
Fas Ligand Protein / metabolism*
Humans
Infant
Infant, Newborn
Interleukin-10 / blood
Interleukin-10 / metabolism*
Lymphoproliferative Disorders / blood
Lymphoproliferative Disorders / diagnosis*
Lymphoproliferative Disorders / genetics
Lymphoproliferative Disorders / metabolism
Middle Aged
Mutation / physiology
Receptors, Antigen, T-Cell, alpha-beta / metabolism*
Syndrome
T-Lymphocytes / metabolism*
T-Lymphocytes / pathology
Young Adult
fas Receptor / genetics*
fas Receptor / physiology

Substances

Biomarkers
CD4 Antigens
CD8 Antigens
Fas Ligand Protein
Receptors, Antigen, T-Cell, alpha-beta
fas Receptor
Interleukin-10