Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS)

• Published in: Blood Vol. 105; no. 6; pp. 2443 - 2448
• Main Authors: Teachey, David T., Manno, Catherine S., Axsom, Kelly M., Andrews, Timothy, Choi, John K., Greenbaum, Barbara H., McMann, Joseph M., Sullivan, Kathleen E., Travis, Susan F., Grupp, Stephan A.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.03.2005; The Americain Society of Hematology
• Subjects: Adolescent; Adult; Apoptosis - immunology; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Biological and medical sciences; Cells, Cultured; Child; Child, Preschool; fas Receptor - immunology; Female; General aspects; Hematologic and hematopoietic diseases; Hematologic Tests; Hematopoietic Stem Cells - immunology; Hematopoietic Stem Cells - pathology; Homeostasis - immunology; Humans; Immunopathology; Infant; Lymphatic Diseases - diagnosis; Lymphatic Diseases - immunology; Lymphatic Diseases - pathology; Lymphoproliferative Disorders - diagnosis; Lymphoproliferative Disorders - immunology; Lymphoproliferative Disorders - pathology; Male; Medical sciences; Other diseases. Hematologic involvement in other diseases; Predictive Value of Tests; Syndrome; T-Lymphocytes - immunology; T-Lymphocytes - pathology; Human; Platelet; Autoimmune lymphoproliferative syndrome; Immune response; Immunophenotype; T-Lymphocyte; Autoimmune disease; Hemopathy; Evans syndrome; Differential diagnostic; Apoptosis
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-09-3542

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.