2002 Fiscal Year Annual Research Report

抗体欠乏をきたす原発性免疫不全症候群の包括的解析:診断と治療の展開

Research Project

Project/Area Number	13470162
Research Institution	Shinshu University
Principal Investigator	小宮山淳信州大学, 医学部, 教授 (50020798)
Co-Investigator(Kenkyū-buntansha)	南雲治夫信州大学, 附属病院, 助手 (20332679) 上松一永信州大学, 医学研究科, 助教授 (60262721)
Keywords	抗体不全 / B細胞 / 免疫学的記憶 / 免疫不全症
Research Abstract	抗体産生は生体防御において主要な役割を演じている。原発性免疫不全症の中で、抗体欠乏を主徴とする免疫不全症はかなりの割合を占め、臨床的にも重要な疾患群となっている。本症おける病因を解明とともに、その責任遺伝子を応用して臨床的に有用な診断や治療法を開発した。全国から収集したX連鎖無ガンマグロブリン血症患者やX連鎖高IgM血症患者の遺伝子解析に加え、新たに臨床導入されたフローサイトメーターによる診断法の有用性を検証した(Gombart et al. Blood 2001)。X連鎖高IgM血症II型については、責任遺伝子AIDの機能解析を行うとともにAIDノックアウトマウスを用いた解析を行った。病因不明の分類不能型免疫不全症に関しては、CD27、ICOS, B7hなどの分子群を中心に多角的な解析を行った(Agematsu et al. Clin Immunol 2002)。また、抗体産生のない重症複合免疫不全症(SCID)のB細胞機能解析(Agematsu et al. Clin Exp Immunol 2001)、ならびにその責任遺伝子、Artemisの本邦初の変異を4家系で同定し報告した(Kobayashi et al. Hum Genet in press)。さらに、NGFR (nerve growth factor receptor)/TNFR (tumor necrosis factor receptor)ファミリーに属するCD27分子をメモリーB細胞のマーカーとして用いて、新生児における抗体産生低下や分類不能型免疫不全症の病因・病態について解析した(Nagumo et al. Blood 2002)。本研究によって、抗体欠乏をきたす既知ならびに原因不明の免疫不全症の病態解析、簡易法を含む診断法の開発、新たな治療法の試みを行なうことができた。

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] Kobayashi N, Agematsu K, Sugita K, Sako M, Nonoyama S, Yachie A, Kumaki S, Tsuchiya S, Ochs HD, Sugita K, Fukushima Y, Komiyama A: "Novel Artemis gene mutations of radiosensitive severe combined immunodeficiency in Japanese families"Hum Genet. (in press).
[Publications] Yamada S, Shinozaki K, Agematsu K.: "Involvement of CD27/CD70 interactions in antigen-specific cytotoxic T-lymphocyte (CTL) activity by perforin-mediated cytotoxicity"Clin Exp Immunol. 130. 424-430 (2002)
[Publications] Kobayashi N, Nagumo H, Agematsu K.: "IL-10 enhances B-cell IgE synthesis by promoting differentiation into plasma cells, a process that is inhibited by CD27/CD70 interaction"Clin. Exp. Immunol. 129. 446-452 (2002)
[Publications] Agematsu K, Futatani T, Hokibara S, Kobayashi H, Takamoto M, Tsukada S, Suzuki H, Koyasu S, Miyawaki T, Sugane K, Komiyama A, Ochs HD.: "Absence of memory B cell in patients with common variable immunodeficiency"Clinical Immunology. 103. 34-42 (2002)
[Publications] Nagumo H, Agematsu K, Kobayashi N, Shinozaki S, Hokibara S, Nagase H, Takamoto M, Yasui K, Sugane S, Komiyama A: "Different process of class switching and somatic hypermutation ; a novel analysis by CD27^-naive B cells"Blood. 99. 567-575 (2002)
[Publications] Shinozaki K, Agematsu K, Yasui K, Nagumo H, Naito H, Naganuma K, Komiyama A: "Familial Mediterranean fever two Japanese families"The Journal of Rheumatology. 29. 1324-1325 (2001)
[Publications] Cui SH, Tanabe F, Terunuma H, Iwatani Y, Nunoi H, Agematsu K, Komiyama A, Nomura A, Ito M: "A thiol proteinase inhibitor, E-64-d, corrects the abnormalities in concanavalin A cap formation and the lysosomal enzyme activity in leucocytes from patients with Chediak-Higashi syndrome by reversing the down-regulated protein kinase C activity"Clin Exp Immunol. 125. 283-290 (2001)
[Publications] Hisashi Nagase, Kazunaga Agematsu, Kiyoshi Kitano, Atsushi Komiyama, Kazuo Sugane: "Mechanism of Hypergammaglobulinemia by Human Immunodeficiency Virus Infection : Circulating Memory B-cell Reduction with Plasmacytosis"Clin. Immunol.. 100. 250-259 (2001)
[Publications] Agematsu K, Haruo Nagumo, Sho Hokibara, Tetsuo Mori, Akihiro Yachie, Hirokazu Kanegane, Toshio Miyawaki., Katsuo Sugita, Hajime Karasuyama: "Atsushi Komiyama. Complete arrest from pro-to pre-B cells in a case of B cell-negative severe combined immunodeficiency (SCID) without recombinase activating gene (RAG) mutations"Clin. Exp. Immunol.. 124. 461-464 (2001)
[Publications] Koji Shinozaki, Kozo Yasui, Kazunaga Agematsu: "Direct B/B-cell interactions in immunoglobulin synthesis"Clin. Exp. Immunol. 124. 386-391 (2001)
[Publications] Gombart AF, Shiohara M, Kwok SH, Agematsu K, Komiyama A, Koeffler HP.: "Neutrophil-specific granule deficiency : homozygous recessive inheritance of a frameshift mutation in the gene encoding transcription factor CCAAT/enhancer binding protein-epsilon"Blood. 97. 2561-2567 (2001)
[Publications] Uehara Y, Kikuchi K, Nakamura T, Nakama H, Agematsu K, Kawakami Y, Maruchi N, Totsuka K: "H202 Produced by Viridans Group Streptococci May Contribute to Inhibition of Methicillin-Resistant Staphylococcus aureus Colonization of Oral Cavities in Newborns"Clin. Infect. Dis.. 32. 1408-1413 (2001)
[Publications] Uehara Y, Kikuchi K, Nakamura T, Nakama H, Agematsu K, Kawakami Y, Maruchi N, Totsuka K.: "Inhibition of Methicillin-Resistant Staphylococcus aureus Colonization of Oral Cavities in Newborns by Viridans Group Streptococci"Clin. Infect. Dis.. 32. 1399-1407 (2001)

2002 Fiscal Year Annual Research Report

抗体欠乏をきたす原発性免疫不全症候群の包括的解析:診断と治療の展開

Principal Investigator

小宮山 淳 信州大学, 医学部, 教授 (50020798)

Research Products

[Publications] Kobayashi N, Agematsu K, Sugita K, Sako M, Nonoyama S, Yachie A, Kumaki S, Tsuchiya S, Ochs HD, Sugita K, Fukushima Y, Komiyama A: "Novel Artemis gene mutations of radiosensitive severe combined immunodeficiency in Japanese families"Hum Genet. (in press).

[Publications] Yamada S, Shinozaki K, Agematsu K.: "Involvement of CD27/CD70 interactions in antigen-specific cytotoxic T-lymphocyte (CTL) activity by perforin-mediated cytotoxicity"Clin Exp Immunol. 130. 424-430 (2002)

[Publications] Kobayashi N, Nagumo H, Agematsu K.: "IL-10 enhances B-cell IgE synthesis by promoting differentiation into plasma cells, a process that is inhibited by CD27/CD70 interaction"Clin. Exp. Immunol. 129. 446-452 (2002)

[Publications] Agematsu K, Futatani T, Hokibara S, Kobayashi H, Takamoto M, Tsukada S, Suzuki H, Koyasu S, Miyawaki T, Sugane K, Komiyama A, Ochs HD.: "Absence of memory B cell in patients with common variable immunodeficiency"Clinical Immunology. 103. 34-42 (2002)

[Publications] Nagumo H, Agematsu K, Kobayashi N, Shinozaki S, Hokibara S, Nagase H, Takamoto M, Yasui K, Sugane S, Komiyama A: "Different process of class switching and somatic hypermutation ; a novel analysis by CD27^-naive B cells"Blood. 99. 567-575 (2002)

[Publications] Shinozaki K, Agematsu K, Yasui K, Nagumo H, Naito H, Naganuma K, Komiyama A: "Familial Mediterranean fever two Japanese families"The Journal of Rheumatology. 29. 1324-1325 (2001)

[Publications] Hisashi Nagase, Kazunaga Agematsu, Kiyoshi Kitano, Atsushi Komiyama, Kazuo Sugane: "Mechanism of Hypergammaglobulinemia by Human Immunodeficiency Virus Infection : Circulating Memory B-cell Reduction with Plasmacytosis"Clin. Immunol.. 100. 250-259 (2001)

[Publications] Koji Shinozaki, Kozo Yasui, Kazunaga Agematsu: "Direct B/B-cell interactions in immunoglobulin synthesis"Clin. Exp. Immunol. 124. 386-391 (2001)

[Publications] Gombart AF, Shiohara M, Kwok SH, Agematsu K, Komiyama A, Koeffler HP.: "Neutrophil-specific granule deficiency : homozygous recessive inheritance of a frameshift mutation in the gene encoding transcription factor CCAAT/enhancer binding protein-epsilon"Blood. 97. 2561-2567 (2001)

[Publications] Uehara Y, Kikuchi K, Nakamura T, Nakama H, Agematsu K, Kawakami Y, Maruchi N, Totsuka K.: "Inhibition of Methicillin-Resistant Staphylococcus aureus Colonization of Oral Cavities in Newborns by Viridans Group Streptococci"Clin. Infect. Dis.. 32. 1399-1407 (2001)

小宮山淳信州大学, 医学部, 教授 (50020798)