1. Subtypes of Familial Hemophagocytic Lymphohistiocytosis in Japan Based on Genetic and Functional Analyses of Cytotoxic T Lymphocytes.
- Author
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Nagai, Kozo, Yamamoto, Ken, Fujiwara, Hiroshi, An, Jun, Ochi, Toshiki, Suemori, Koichiro, Yasumi, Takahiro, Tauchi, Hisamichi, Koh, Katsuyoshi, Sato, Maho, Morimoto, Akira, Heike, Toshio, Ishii, Eiichi, and Yasukawa, Masaki
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INFANT diseases , *LYMPHOCYTES , *GENETIC mutation , *GRANULATION , *FUNCTIONAL analysis - Abstract
Background: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare disease of infancy or early childhood. To clarify the incidence and subtypes of FHL in Japan, we performed genetic and functional analyses of cytotoxic T lymphocytes (CTLs) in Japanese patients with FHL. Design and Methods: Among the Japanese children with hemophagocytic lymphohistiocytosis (HLH) registered at our laboratory, those with more than one of the following findings were eligible for study entry under a diagnosis of FHL: positive for known genetic mutations, a family history of HLH, and impaired CTL-mediated cytotoxicity. Mutations of the newly identified causative gene for FHL5, STXBP2, and the cytotoxicity and degranulation activity of CTLs in FHL patients, were analyzed. Results: Among 31 FHL patients who satisfied the above criteria, PRF1 mutation was detected in 17 (FHL2) and UNC13D mutation was in 10 (FHL3). In 2 other patients, 3 novel mutations of STXBP2 gene were confirmed (FHL5). Finally, the remaining 2 were classified as having FHL with unknown genetic mutations. In all FHL patients, CTL-mediated cytotoxicity was low or deficient, and degranulation activity was also low or absent except FHL2 patients. In 2 patients with unknown genetic mutations, the cytotoxicity and degranulation activity of CTLs appeared to be deficient in one patient and moderately impaired in the other. Conclusions: FHL can be diagnosed and classified on the basis of CTL-mediated cytotoxicity, degranulation activity, and genetic analysis. Based on the data obtained from functional analysis of CTLs, other unknown gene(s) responsible for FHL remain to be identified. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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