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.
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.
Magerus-Chatinet
Aude
A
Inserm U768, Paris, France.
Stolzenberg
Marie-Claude
MC
Loffredo
Maria S
MS
Neven
Bénédicte
B
Schaffner
Catherine
C
Ducrot
Nicolas
N
Arkwright
Peter D
PD
Bader-Meunier
Brigitte
B
Barbot
José
J
Blanche
Stéphane
S
Casanova
Jean-Laurent
JL
Debré
Marianne
M
Ferster
Alina
A
Fieschi
Claire
C
Florkin
Benoit
B
Galambrun
Claire
C
Hermine
Olivier
O
Lambotte
Olivier
O
Solary
Eric
E
Thomas
Caroline
C
Le Deist
Francoise
F
Picard
Capucine
C
Fischer
Alain
A
Rieux-Laucat
Frédéric
F
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
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