Subject(s)
Bone Marrow Diseases/blood , Bone Marrow Diseases/genetics , Chromosomes, Human, Pair 7/genetics , Exocrine Pancreatic Insufficiency/blood , Exocrine Pancreatic Insufficiency/genetics , Hematopoiesis/physiology , Lipomatosis/blood , Lipomatosis/genetics , Loss of Heterozygosity , Bone Marrow Diseases/pathology , Chromosome Aberrations , DNA Copy Number Variations , Exocrine Pancreatic Insufficiency/pathology , Female , Humans , Infant , Lipomatosis/pathology , Shwachman-Diamond SyndromeABSTRACT
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.
Subject(s)
Apoptosis/immunology , Autoimmune Diseases/immunology , Hematopoietic Stem Cells/immunology , Lymphoproliferative Disorders/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Autoimmune Diseases/pathology , Cells, Cultured , Child , Child, Preschool , Female , Hematologic Tests , Hematopoietic Stem Cells/pathology , Homeostasis/immunology , Humans , Infant , Lymphatic Diseases/diagnosis , Lymphatic Diseases/immunology , Lymphatic Diseases/pathology , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/pathology , Male , Predictive Value of Tests , Syndrome , T-Lymphocytes/pathology , fas Receptor/immunologyABSTRACT
Transcranial Doppler ultrasonography provides a noninvasive method of predicting stroke risk in children with sickle cell disease. Elevated cerebral blood flow velocity in the terminal internal carotid or middle cerebral artery is associated with an increased stroke risk, but the clinical significance of elevated velocities in the other large intracranial vessels is unknown. The authors report stroke in two children with sickle cell disease and high blood flow velocity limited to the anterior cerebral artery. This suggests that elevated velocity in this vessel may be associated with an increased risk of stroke.