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

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by splenomegaly, lymphadenopathy, hypergammaglobulinemia, accumulation of double-negative TCRαβ+ CD4−CD8− T cells (DNT cells), and autoimmunity. Previously, DNT cell detection and a functional defect of T cells in a FAS-induced apoptosi...

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Published in:Blood 2009-03, Vol.113 (13), p.3027-3030
Main Authors: Magerus-Chatinet, Aude, Stolzenberg, Marie-Claude, Loffredo, Maria S., Neven, Bénédicte, Schaffner, Catherine, Ducrot, Nicolas, Arkwright, Peter D., Bader-Meunier, Brigitte, Barbot, José, Blanche, Stéphane, Casanova, Jean-Laurent, Debré, Marianne, Ferster, Alina, Fieschi, Claire, Florkin, Benoit, Galambrun, Claire, Hermine, Olivier, Lambotte, Olivier, Solary, Eric, Thomas, Caroline, Le Deist, Francoise, Picard, Capucine, Fischer, Alain, Rieux-Laucat, Frédéric
Format: Article
Language:English
Subjects:
Adolescent
Adult
Autoimmune Diseases - blood
Autoimmune Diseases - diagnosis
Autoimmune Diseases - genetics
Autoimmune Diseases - metabolism
Biomarkers - blood
Biomarkers - metabolism
Case-Control Studies
CD4 Antigens - blood
CD4 Antigens - metabolism
CD8 Antigens - blood
CD8 Antigens - metabolism
Child
Child, Preschool
Fas Ligand Protein - blood
Fas Ligand Protein - metabolism
fas Receptor - genetics
fas Receptor - physiology
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
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Summary:Autoimmune lymphoproliferative syndrome (ALPS) is characterized by splenomegaly, lymphadenopathy, hypergammaglobulinemia, accumulation of double-negative TCRαβ+ 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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2008-09-179630