Subtypes of Familial Hemophagocytic Lymphohistiocytosis in Japan Based on Genetic and Functional Analyses of Cytotoxic T Lymphocytes
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{"title"=>"Subtypes of familial hemophagocytic lymphohistiocytosis in Japan based on genetic and functional analyses of cytotoxic T lymphocytes", "type"=>"journal", "authors"=>[{"first_name"=>"Kozo", "last_name"=>"Nagai", "scopus_author_id"=>"55602549700"}, {"first_name"=>"Ken", "last_name"=>"Yamamoto", "scopus_author_id"=>"55613983600"}, {"first_name"=>"Hiroshi", "last_name"=>"Fujiwara", "scopus_author_id"=>"56585248400"}, {"first_name"=>"Jun", "last_name"=>"An", "scopus_author_id"=>"36698788400"}, {"first_name"=>"Toshiki", "last_name"=>"Ochi", "scopus_author_id"=>"24335514100"}, {"first_name"=>"Koichiro", "last_name"=>"Suemori", "scopus_author_id"=>"24336759200"}, {"first_name"=>"Takahiro", "last_name"=>"Yasumi", "scopus_author_id"=>"6603644396"}, {"first_name"=>"Hisamichi", "last_name"=>"Tauchi", "scopus_author_id"=>"7007010349"}, {"first_name"=>"Katsuyoshi", "last_name"=>"Koh", "scopus_author_id"=>"57197321700"}, {"first_name"=>"Maho", "last_name"=>"Sato", "scopus_author_id"=>"36997967700"}, {"first_name"=>"Akira", "last_name"=>"Morimoto", "scopus_author_id"=>"7103302942"}, {"first_name"=>"Toshio", "last_name"=>"Heike", "scopus_author_id"=>"7003595166"}, {"first_name"=>"Eiichi", "last_name"=>"Ishii", "scopus_author_id"=>"26643273800"}, {"first_name"=>"Masaki", "last_name"=>"Yasukawa", "scopus_author_id"=>"7103398346"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"360095142", "sgr"=>"78649779989", "doi"=>"10.1371/journal.pone.0014173", "scopus"=>"2-s2.0-78649779989", "pmid"=>"21152410"}, "id"=>"40f278dd-0f9d-3329-a866-67a075b657f9", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/subtypes-familial-hemophagocytic-lymphohistiocytosis-japan-based-genetic-functional-analyses-cytotox-3", "reader_count"=>4, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>2, "Student > Master"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>2, "Student > Master"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/815915"], "description"=>"<p>Flow cytometric analysis of CD107a expression was performed using CD8<sup>+</sup> T-cell lines generated from a healthy individual and FHL patients, as detailed in the text. Left panel of each column shows CD107a expression in CD8<sup>+</sup> T cells without any stimulation. Right panel of each column shows CD107a expression in CD8<sup>+</sup> T cells stimulated with KI-LCL cells.</p>", "links"=>[], "tags"=>["alloantigen-specific", "t-cell"], "article_id"=>486272, "categories"=>["Medicine", "Genetics", "Immunology"], "users"=>["Kozo Nagai", "Ken Yamamoto", "Hiroshi Fujiwara", "Jun An", "Toshiki Ochi", "Koichiro Suemori", "Takahiro Yasumi", "Hisamichi Tauchi", "Katsuyoshi Koh", "Maho Sato", "Akira Morimoto", "Toshio Heike", "Eiichi Ishii", "Masaki Yasukawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014173.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CD107a_expression_of_alloantigen_specific_CD8_T_cell_lines_/486272", "title"=>"CD107a expression of alloantigen-specific CD8<sup>+</sup> T-cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-11-30 01:44:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/815495"], "description"=>"<p>(A) Sequencing analysis of 4 patients with non-FHL2/3/4 and detection of 3 novel mutations in 2 of them: a compound heterozygous mutation of 292_294delGCG resulting in Ala98del at exon 5 (upper panel) and 88-1g>a in intron 2 (lower panel) in one patient (UPN28), and a homozygous mutation of 1243-1246AGTG resulting in Ser415ArgfsX6 at exon 15 in the other (UPN29). (B) Expression of <i>STXBP2</i> cDNA in UPN28 with 88-1g>a mutation. Schematic representation of positions of the primers for RT-PCR and 88-1g>a mutation is shown in the upper panel, and for RT-PCR products from 88-1G>A mutation of <i>STXBP2</i> in the lower panel. The expected 350-bp product of <i>STXBP2</i> exons 1–5 was detected in a healthy control individual, whereas extra larger- and smaller-sized products were detected in UPN28 (arrow). (C) Sequence analysis revealed that the 88-1g>a mutation retained the entire intron 2 (243 bp) in the cDNA. This insertion is predicted to cause addition of 81 amino acids to the N-terminal region of the large Sec1 domain of the Munc18-2 protein (upper panel). Sequence analysis of the smaller fragment revealed that the mutation caused skipping of exon 3 (82 bp), resulting in a frame shift and translational arrest after an additional 20 amino acids (lower panel).</p>", "links"=>[], "tags"=>["genetics and genomics/genetics of the immune system", "immunology/genetics of the immune system", "hematology/pediatric hematology"], "article_id"=>485849, "categories"=>["Medicine", "Genetics", "Immunology"], "users"=>["Kozo Nagai", "Ken Yamamoto", "Hiroshi Fujiwara", "Jun An", "Toshiki Ochi", "Koichiro Suemori", "Takahiro Yasumi", "Hisamichi Tauchi", "Katsuyoshi Koh", "Maho Sato", "Akira Morimoto", "Toshio Heike", "Eiichi Ishii", "Masaki Yasukawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014173.g001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_STXBP2_mutations_/485849", "title"=>"Identification of <i>STXBP2</i> mutations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-11-30 01:37:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/815701"], "description"=>"<p>CD8<sup>+</sup> T-cell lines were generated from the PBMCs of the patients with FHL and healthy individuals as controls by stimulation with allogeneic B-LCL (KI-LCL) cells. Responder cells were co-cultured with or without KI-LCL or TA-LCL, which shared no HLA antigens with KI-LCL, in the presence or absence of anti-HLA class I monoclonal antibody for 24 hours. IFN-γ production was measured by ELISA. All FHL patients showed normal production of IFN-γ. The HLA type of KI-LCL is HLA-A01/30, B13/17, Cw6/-, DRB1*0701/*0701, and that of TA-LCL is HLA-A24/26, B62/-, Cw4/w9, DRB1*0405/*0901. NS indicates <i>PRF1</i> nonsense mutation.</p>", "links"=>[], "tags"=>["alloantigen-specific"], "article_id"=>486056, "categories"=>["Medicine", "Genetics", "Immunology"], "users"=>["Kozo Nagai", "Ken Yamamoto", "Hiroshi Fujiwara", "Jun An", "Toshiki Ochi", "Koichiro Suemori", "Takahiro Yasumi", "Hisamichi Tauchi", "Katsuyoshi Koh", "Maho Sato", "Akira Morimoto", "Toshio Heike", "Eiichi Ishii", "Masaki Yasukawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014173.g003", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IFN_production_by_alloantigen_specific_CD8_T_cell_lines_/486056", "title"=>"IFN-γ production by alloantigen-specific CD8<sup>+</sup> T cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-11-30 01:40:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/815643"], "description"=>"<p>Expression of Munc18-2 protein in each CD8<sup>+</sup> T-cell line that had been stimulated with allogeneic B-LCL cells was analyzed by Western blotting using anti-Munc18-2 antibody. Munc18-2 protein was abundantly detected at 67 kDa in CTL lines established from healthy control individuals and 2 non-FHL2/3/4/5 patients (UPN30, and UPN31).</p>", "links"=>[], "tags"=>["blot", "munc18-2"], "article_id"=>485993, "categories"=>["Medicine", "Genetics", "Immunology"], "users"=>["Kozo Nagai", "Ken Yamamoto", "Hiroshi Fujiwara", "Jun An", "Toshiki Ochi", "Koichiro Suemori", "Takahiro Yasumi", "Hisamichi Tauchi", "Katsuyoshi Koh", "Maho Sato", "Akira Morimoto", "Toshio Heike", "Eiichi Ishii", "Masaki Yasukawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014173.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Western_blot_analysis_of_Munc18_2_protein_expression_/485993", "title"=>"Western blot analysis of Munc18-2 protein expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-11-30 01:39:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/815814"], "description"=>"<p>CD8<sup>+</sup> T-cell lines were generated from the PBMCs of the patients with FHL and 24 healthy individuals as controls by stimulation with allogeneic B-LCL (KI-LCL) cells. Their cytotoxicity was determined against allogeneic KI-LCL (clear circles) and against allogeneic TA-LCL (solid circles). All FHL patients showed various degrees of impairment of CTL-mediated cytotoxicity against allogeneic B-LCLs. NS indicates <i>PRF1</i> nonsense mutation.</p>", "links"=>[], "tags"=>["alloantigen-specific", "t-cell"], "article_id"=>486170, "categories"=>["Medicine", "Genetics", "Immunology"], "users"=>["Kozo Nagai", "Ken Yamamoto", "Hiroshi Fujiwara", "Jun An", "Toshiki Ochi", "Koichiro Suemori", "Takahiro Yasumi", "Hisamichi Tauchi", "Katsuyoshi Koh", "Maho Sato", "Akira Morimoto", "Toshio Heike", "Eiichi Ishii", "Masaki Yasukawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014173.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytotoxicity_of_alloantigen_specific_CD8_T_cell_lines_/486170", "title"=>"Cytotoxicity of alloantigen-specific CD8<sup>+</sup> T-cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-11-30 01:42:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/816021"], "description"=>"<p>UPN, unique patient number; M, male; F, female; -, not detected, NT, not tested.</p><p>In parenthesis, M means missense mutation, N means nonsense mutation, and S means splicing abnormality.</p>", "links"=>[], "tags"=>["mutations", "31"], "article_id"=>486379, "categories"=>["Medicine", "Genetics", "Immunology"], "users"=>["Kozo Nagai", "Ken Yamamoto", "Hiroshi Fujiwara", "Jun An", "Toshiki Ochi", "Koichiro Suemori", "Takahiro Yasumi", "Hisamichi Tauchi", "Katsuyoshi Koh", "Maho Sato", "Akira Morimoto", "Toshio Heike", "Eiichi Ishii", "Masaki Yasukawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014173.t001", "stats"=>{"downloads"=>3, "page_views"=>39, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genetic_mutations_of_PRF1_UNC13D_STX11_and_STXBP2_identified_in_31_patients_/486379", "title"=>"Genetic mutations of <i>PRF1</i>, <i>UNC13D</i>, <i>STX11</i>, and <i>STXBP2</i> identified in 31 patients.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-11-30 01:46:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/406633"], "description"=>"<div><h3>Background</h3><p>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.</p><h3>Design and Methods</h3><p>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, <em>STXBP2</em>, and the cytotoxicity and degranulation activity of CTLs in FHL patients, were analyzed.</p><h3>Results</h3><p>Among 31 FHL patients who satisfied the above criteria, <em>PRF1</em> mutation was detected in 17 (FHL2) and <em>UNC13D</em> mutation was in 10 (FHL3). In 2 other patients, 3 novel mutations of <em>STXBP2</em> 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.</p><h3>Conclusions</h3><p>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.</p></div>", "links"=>[], "tags"=>["subtypes", "familial", "hemophagocytic", "lymphohistiocytosis", "japan", "based", "analyses", "cytotoxic", "lymphocytes"], "article_id"=>140332, "categories"=>["Medicine", "Genetics", "Immunology"], "users"=>["Kozo Nagai", "Ken Yamamoto", "Hiroshi Fujiwara", "Jun An", "Toshiki Ochi", "Koichiro Suemori", "Takahiro Yasumi", "Hisamichi Tauchi", "Katsuyoshi Koh", "Maho Sato", "Akira Morimoto", "Toshio Heike", "Eiichi Ishii", "Masaki Yasukawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014173", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Subtypes_of_Familial_Hemophagocytic_Lymphohistiocytosis_in_Japan_Based_on_Genetic_and_Functional_Analyses_of_Cytotoxic_T_Lymphocytes/140332", "title"=>"Subtypes of Familial Hemophagocytic Lymphohistiocytosis in Japan Based on Genetic and Functional Analyses of Cytotoxic T Lymphocytes", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-11-30 00:05:32"}

PMC Usage Stats | Further Information

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