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.

journal_name

Blood

journal_title

Blood

authors

Tabata Y,Villanueva J,Lee SM,Zhang K,Kanegane H,Miyawaki T,Sumegi J,Filipovich AH

doi

10.1182/blood-2004-09-3651

subject

Has Abstract

pub_date

2005-04-15 00:00:00

pages

3066-71

issue

8

eissn

0006-4971

issn

1528-0020

pii

2004-09-3651

journal_volume

105

pub_type

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