title: 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.
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.
authors.affiliation: Inserm U768, Paris, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Magerus-Chatinet
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Stolzenberg
authors.forename: Maria S
authors.initials: MS
authors.lastname: Loffredo
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Neven
authors.forename: Catherine
authors.initials: C
authors.lastname: Schaffner
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ducrot
authors.forename: Peter D
authors.initials: PD
authors.lastname: Arkwright
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bader-Meunier
authors.forename: José
authors.initials: J
authors.lastname: Barbot
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Marianne
authors.initials: M
authors.lastname: Debré
authors.forename: Alina
authors.initials: A
authors.lastname: Ferster
authors.forename: Claire
authors.initials: C
authors.lastname: Fieschi
authors.forename: Benoit
authors.initials: B
authors.lastname: Florkin
authors.forename: Claire
authors.initials: C
authors.lastname: Galambrun
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.forename: Caroline
authors.initials: C
authors.lastname: Thomas
authors.forename: Francoise
authors.initials: F
authors.lastname: Le Deist
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rieux-Laucat
mesh_terms: D000293:Adolescent; D000328:Adult; D001327:Autoimmune Diseases / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D015704:CD4 Antigens / Q000097:blood / Q000378:metabolism; D016827:CD8 Antigens / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D053222:Fas Ligand Protein / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism*; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D013577:Syndrome; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult; D019014:fas Receptor / Q000235:genetics* / Q000502:physiology
chemical_list: D015415:Biomarkers; D015704:CD4 Antigens; D016827:CD8 Antigens; D053222:Fas Ligand Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019014:fas Receptor; D016753:Interleukin-10