Characterization of Epstein-Barr virus (EBV)-infected cells in EBV-associated hemophagocytic lymphohistiocytosis in two patients with X-linked lymphoproliferative syndrome type 1 and type 2.
BACKGROUND
X-linked lymphoproliferative syndrome (XLP) is a rare inherited immunodeficiency by an extreme vulnerability to Epstein-Barr virus (EBV) infection, frequently resulting in hemophagocytic lymphohistiocytosis (HLH). XLP are now divided into type 1 (XLP-1) and type 2 (XLP-2), which are caused by mutations of SH2D1A/SLAM-associated protein (SAP) and X-linked inhibitor of apoptosis protein (XIAP) genes, respectively. The diagnosis of XLP in individuals with EBV-associated HLH (EBV-HLH) is generally difficult because they show basically similar symptoms to sporadic EBV-HLH. Although EBV-infected cells in sporadic EBV-HLH are known to be mainly in CD8+ T cells, the cell-type of EBV-infected cells in EBV-HLH seen in XLP patients remains undetermined.


METHODS
EBV-infected cells in two patients (XLP-1 and XLP-2) presenting EBV-HLH were evaluated by in EBER-1 in situ hybridization or quantitative PCR methods.


RESULTS
Both XLP patients showed that the dominant population of EBV-infected cells was CD19+ B cells, whereas EBV-infected CD8+ T cells were very few.


CONCLUSIONS
In XLP-related EBV-HLH, EBV-infected cells appear to be predominantly B cells. B cell directed therapy such as rituximab may be a valuable option in the treatment of EBV-HLH in XLP patients.
Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan. kanegane@med.u-toyama.ac.jp.
Xi
X
Yang
Taizo
T
Wada
Ken-Ichi
K
Imadome
Naonori
N
Nishida
Takeo
T
Mukai
Mitsuhiro
M
Fujiwara
Haruka
H
Kawashima
Fumiyo
F
Kato
Shigeyoshi
S
Fujiwara
Akihiro
A
Yachie
Xiaodong
X
Zhao
Toshio
T
Miyawaki
Hirokazu
H
Kanegane