Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS).
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.
Teachey
David T
DT
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.
Manno
Catherine S
CS
Axsom
Kelly M
KM
Andrews
Timothy
T
Choi
John K
JK
Greenbaum
Barbara H
BH
McMann
Joseph M
JM
Sullivan
Kathleen E
KE
Travis
Susan F
SF
Grupp
Stephan A
SA
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
D019014:fas Receptor