title: The apoptosis-1/Fas protein in human systemic lupus erythematosus.
abstract: Three independent mutations involving the apoptosis-1 (APO-1)/Fas receptor or its putative ligand have led to lupuslike diseases associated with lymphadenopathy in different strains of mice. To determine whether humans with SLE also have a defect in this apotosis pathway, we analyzed the expression of APO-1 on freshly isolated blood mononuclear cells and on lymphocytes activated in vitro using flow cytometry and the monoclonal antibody anti-APO-1. Significantly higher level of APO-1 expression were detected on freshly isolated peripheral B cells and both CD4+ and CD8+ T lymphocyte populations obtained from lupus patients when compared with normal controls (P < 0.001). Almost 90% of the cells that stained positive for APO-1 also expressed the CD29 antigen, suggesting that APO-1 was upregulated after lymphocyte activation in vivo. No defect in APO-1 regulation was detected after activation of SLE T (with anti-CD3) or B (with Staphylococcus aureus Cowan 1) lymphocytes in the presence of IL-2 in vitro. Similarly, the anti-APO-1 antibody induced apoptosis in 74 +/- 5% of activated SLE T cells in vitro compared with 79 +/- 6% of the normal controls (P > 0.05). These results reveal that, while APO-1/Fas may play an important role in the regulation of lymphocyte survival in SLE, no consistent defect in the expression or function of the receptor could be detected in these studies.
authors.affiliation: Hospital for Special Surgery, Cornell University Medical Center, New York 10021.
authors.forename: E
authors.initials: E
authors.lastname: Mysler
authors.forename: P
authors.initials: P
authors.lastname: Bini
authors.forename: J
authors.initials: J
authors.lastname: Drappa
authors.forename: P
authors.initials: P
authors.lastname: Ramos
authors.forename: S M
authors.initials: SM
authors.lastname: Friedman
authors.forename: P H
authors.initials: PH
authors.lastname: Krammer
authors.forename: K B
authors.initials: KB
authors.lastname: Elkon
mesh_terms: D000954:Antigens, Surface / Q000032:analysis*; D017209:Apoptosis; D002478:Cells, Cultured; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008214:Lymphocytes / Q000737:chemistry / Q000502:physiology; D011956:Receptors, Cell Surface / Q000032:analysis*; D019014:fas Receptor
chemical_list: D000954:Antigens, Surface; D011956:Receptors, Cell Surface; D019014:fas Receptor