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, lymphdenopathy, hypergammaglobu-linemia, 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. © 2009 by The American Society of Hematology.