title: Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS).
abstract: Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of disrupted lymphocyte homeostasis. Clinical manifestations of ALPS vary but typically include autoimmune cytopenias, organomegaly, lymphadenopathy, and increased risk of malignancies. A similar spectrum of symptoms may be seen in some patients with Evans syndrome (ES), a hematologic disorder defined by autoimmune destruction of at least 2 hematologic cell types. We hypothesized that a subset of patients diagnosed with ES may have ALPS. We screened 12 children with ES by flow cytometric analysis for CD4-/CD8- (double negative) T cells (DNTs) and with the definitive test for ALPS, defective in vitro Fas-mediated apoptosis. Six of the patients had elevated DNTs, suggestive of ALPS and also had defective Fas-mediated apoptosis. The other 6 patients displayed normal T-cell apoptosis; 5 of whom had normal DNTs, and 1 had a borderline result. Thus, 7 (58%) of 12 patients with ES had elevated DNTs suggestive of ALPS, with functional confirmation in 6 of 7. This suggests that analysis of DNTs may be a sensitive first-line screening test, serving as a marker of patients who should undergo definitive testing for ALPS. Our data further suggest that a number of patients with ES may have ALPS, a novel finding with important therapeutic implications.
authors.affiliation: Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, ARC 902, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Teachey
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Manno
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Axsom
authors.forename: Timothy
authors.initials: T
authors.lastname: Andrews
authors.forename: John K
authors.initials: JK
authors.lastname: Choi
authors.forename: Barbara H
authors.initials: BH
authors.lastname: Greenbaum
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McMann
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Sullivan
authors.forename: Susan F
authors.initials: SF
authors.lastname: Travis
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Grupp
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006403:Hematologic Tests; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000473:pathology; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007223:Infant; D008206:Lymphatic Diseases / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D008297:Male; D011237:Predictive Value of Tests; D013577:Syndrome; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D019014:fas Receptor / Q000276:immunology
chemical_list: D019014:fas Receptor