Investigation of suspected deficient Fas‐mediated apoptosis in a father and son

Abstract

Background A 2-year-old boy presented with symptoms consistent with a diagnosis of autoimmune lymphoproliferative syndrome (ALPS). His father had been splenectomized at age 12 with similar symptoms. ALPS is a rare hereditary syndrome that may result from a functional defect in Fas-mediated apoptosis. Methods Peripheral blood lymphocytes (PBL) and splenic lymphocytes from the patient and PBL from his father and a normal control were analyzed for surface Fas expression. They were then stimulated with an anti-Fas monoclonal antibody (DX2). Apoptosis was assayed by flow cytometry at 0, 20, 28, and 34 h. Results There was no significant difference in expression of Fas (CD95) in the PBL of the patient, his father, or the normal control, or the splenic lymphocytes. Compared with the normal control, the PBL of the patient and his father failed to progress to apoptosis. They also contained a markedly elevated proportion of CD3+CD4−CD8− “double-negative” cells. Conclusions PBL from both the patient and his father expressed CD95, but failed to proceed to apoptosis after stimulation, suggesting a functional defect. These results and the clinical presentation are consistent with published descriptions of ALPS. Cytometry 43:195–198, 2001. © 2001 Wiley-Liss, Inc.