title: Rapid detection of intracellular SH2D1A protein in cytotoxic lymphocytes from patients with X-linked lymphoproliferative disease and their family members.
abstract: Mutations in the SH2D1A gene have been described in most patients with the clinical syndrome of X-linked lymphoproliferative disease (XLP). The diagnosis of XLP is still difficult given its clinical heterogeneity and the lack of a readily available rapid diagnostic laboratory test, particularly in patients without a family history of XLP. XLP should always be a consideration in males with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH). Four-color flow cytometric analysis was used to establish normal patterns of SH2D1A protein expression in lymphocyte subsets for healthy subjects. Three of 4 patients with XLP, as confirmed by the detection of mutations in the SH2D1A gene, had minimal intracellular SH2D1A protein in all cytotoxic cell types. The remaining patient lacked intracellular SH2D1A protein in CD56+ natural killer (NK) and T lymphocytes and had an abnormal bimodal pattern in CD8+ T cells. Carriers of SH2D1A mutations had decreased SH2D1A protein staining patterns compared with healthy controls. Eleven males with clinical syndromes consistent with XLP, predominantly EBV-HLH, had patterns of SH2D1A protein expression similar to those of healthy controls. Four-color flow cytometry provides diagnostic information that may speed the identification of this fatal disease, differentiating it from other causes of EBV-HLH.
authors.affiliation: Division of Hematology/Oncology and Division of Human Genetics, Children's Hospital Medical Center, MLC 7015, Cincinnati, OH 45229-3039, USA. yasuhiro.tabata@cchmc.org
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tabata
authors.forename: Joyce
authors.initials: J
authors.lastname: Villanueva
authors.forename: Susan Molleran
authors.initials: SM
authors.lastname: Lee
authors.forename: Kejian
authors.initials: K
authors.lastname: Zhang
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
authors.forename: Janos
authors.initials: J
authors.lastname: Sumegi
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D005820:Genetic Testing; D006801:Humans; D015151:Immunoblotting; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008232:Lymphoproliferative Disorders / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein