Pathophysiological analysis and clinical application of oligosaccharide alterations in inflammatory bowel disease

• Project/Area Number: 22790643
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Osaka University
• Principal Investigator: SHINZAKI Shinichiro 大阪大学, 大学院・医学系研究科, 助教 (60546860)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 下部消化管学(小腸、大腸) / 炎症性腸疾患 / 糖鎖 / IgG / B細胞 / インフリキシマブ / B4GaｌT / B4GalT

Research Abstract

Focused on the increase in agalactosyl IgG in patients with inflammatory bowel disease (IBD), the pathophysiological roles of oligosaccharide alterations on immunoglobulin and immune cells were investigated using colitis model. For clinical application, the relationship between oligosaccharide alterations and patient characteristics in IBD patients were also clarified.

Research Products

• [Journal Article] Lectin-based immunoassay for aberrant IgG glycosylation as the biomarker for Crohn's disease (2013)
  • Author(s): Shinzaki S., Kuroki E., Iijima H., Takehara T ., Miyoshi E., et al
  • Journal Title: Inflamm Bowel Dis Volume: 19(2):321-331
  • Peer Reviewed
• [Journal Article] Lectin-based Immunoassay for Aberrant IgG Glycosylation as the Biomarker for Crohn's Disease (2013)
  • Author(s): Shinzaki S.
  • Journal Title: Inflamm Bowel Dis. Volume: 19(2) Pages: 321-331
  • Peer Reviewed
• [Journal Article] Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in ulcerative colitis (2012)
  • Author(s): Serada S, Fujimoto M, Shinzaki S, Naka T, et al
  • Journal Title: Inflamm Bowel Dis Volume: 18(11):2169-79
  • Peer Reviewed
• [Journal Article] Altered oligosaccharide structures reduce colitis induction in mice defective in β-1,4-galactosyltransferase (2012)
  • Author(s): Shinzaki S, Iijima H, Fujii H, Takehara T, Miyoshi E, et al.
  • Journal Title: Gastroenterology Volume: 142(5):1172-82
  • Peer Reviewed
• [Journal Article] The Importance of Vitamins D and K for the bone health and immune function in Inflammatory Bowel Disease (2012)
  • Author(s): Iijima H, Shinzaki S, Tsujii M, Takehara T
  • Journal Title: Curr Opin Clin Nutr Volume: 15(6):635-40
  • Peer Reviewed
• [Journal Article] N-Acetylglucosaminyltransferase V regulates TGF-β response in hepatic stellate cells and the progression of steatohepatitis (2012)
  • Author(s): Kamada Y, Shinzaki S, Takehara T, Miyoshi E, et al.
  • Journal Title: Glycobiology Volume: 22(6):778-87
  • Peer Reviewed
• [Journal Article] Deficiency of N-acetylgalactosamine in O-linked oligosaccharides of IgA is a novel biologic marker for Crohn's disease (2012)
  • Author(s): Inoue T, Iijima H, Shinzaki S, Takehara T, et al
  • Journal Title: Inflamm Bowel Dis Volume: 18(9): 1723-34
  • Peer Reviewed
• [Journal Article] 最新の疾患バイオマーカー研究-より適切な診療を目指して- 疾患バイオマーカーの臨床研究 (2012)
  • Author(s): 飯島英樹, 新崎信一郎, 辻井正彦, 竹原徹郎
  • Journal Title: 炎症性腸疾患 日本臨床 Volume: 70巻 5号 Pages: 869-873
• [Journal Article] シグナル伝達を理解するために必要な知識糖鎖修飾によるシグナル伝達制御 (2012)
  • Author(s): 新崎信一郎, 島佐知子, 飯島英樹
  • Journal Title: 分子消化器病 Volume: 9巻 1号 Pages: 63-67
• [Journal Article] The importance of vitamins D and K for the bone health and immune function in inflammatory bowel disease. (2012)
  • Author(s): Iijima H.
  • Journal Title: Curr Opin Clin Nutr Metab Care. Volume: 15(6) Issue: 6 Pages: 635-40
  • DOI: 10.1097/mco.0b013e328357f623
  • Peer Reviewed
• [Journal Article] Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in ulcerative colitis (2012)
  • Author(s): Serada S, Fujimoto M, Terabe F, Iijima H, Shinzaki S, Matsuzaki S, Ohkawara T, Nezu R, Nakajima S, Kobayashi T, Plevy SE, Takehara T, Naka T
  • Journal Title: Inflamm Bowel Dis Volume: (in press) Issue: 11 Pages: 2169-79
  • DOI: 10.1002/ibd.22936
  • Peer Reviewed
• [Journal Article] Altered oligosaccharide structures contribute to ameliorate murine colitis defective in beta 1,4 galactosyltransferase I. (2012)
  • Author(s): Shinzaki S, Miyoshi E, et al.
  • Journal Title: Gastroenterology Volume: 142(5) Issue: 5 Pages: 1172-82
  • DOI: 10.1053/j.gastro.2012.02.008
  • Peer Reviewed
• [Journal Article] N-Acetylglucosaminyltransferase V regulates TGF- response in hepatic stellate cells and the progression of steatohepatitis. (2012)
  • Author(s): Kamada Y, Miyoshi E, et al.
  • Journal Title: Glycobiology Volume: 22(6) Issue: 6 Pages: 778-87
  • DOI: 10.1093/glycob/cws012
  • Peer Reviewed
• [Journal Article] Deficiency of N-acetylgalactosamine in O-linked oligosaccharides of IgA is a novel biologic marker for inflammatory bowel diseases. (2012)
  • Author(s): InoueT, Miyoshi E, et al.
  • Journal Title: IBD Journal Volume: 18(9) Issue: 9 Pages: 1723-34
  • DOI: 10.1002/ibd.22876
  • Peer Reviewed
• [Journal Article] Association of Vitamin K Deficiency with Bone Metabolism and Clinical Disease Activity in Inflammatory Bowel Disease (2011)
  • Author(s): Nakajima S, Iijima H, Shinzaki S, Hayashi N, et al.
  • Journal Title: Nutrition Volume: 27(10):1023-8
  • Peer Reviewed
• [Journal Article] Functional analysis of agalactosyl IgG in inflammatory bowel disease patients (2011)
  • Author(s): Nakajima S, Iijima H, Shinzaki S, Hayashi N, et al.
  • Journal Title: Inflamm Bowel Dis Volume: 17(4):927-36
  • NAID: 10028268520
  • Peer Reviewed
• [Journal Article] Comparative Analysis of the Effects of Anti-IL-6 Receptor mAb and Anti-TNF mAb Treatment on CD4+ T Cell Responses in Murine Colitis (2011)
  • Author(s): T erabe F, Fujimoto M, Shinzaki S, Naka T, et al.
  • Journal Title: Inflamm Bowel Dis Volume: 17(2):491-502
  • Peer Reviewed
• [Journal Article] IBD と炎症性サイトカイン(第4回) (2011)
  • Author(s): 飯島英樹, 新崎信一郎, 辻井正彦, 竹原徹郎
  • Journal Title: IL-12/IL-23 G.I.Research Volume: 19巻 5号 Pages: 501-506
• [Journal Article] GP のためのセミナー 先端医学トレンド 炎症性腸疾患のバイオマーカー (2011)
  • Author(s): 新崎信一郎
  • Journal Title: クリ シアン Volume: 58巻 8号 Pages: 1001-1006
• [Journal Article] 炎症性腸疾患患者におけるMannan Binding Lectin の分布とガラクトース欠損 IgG の役割 (2011)
  • Author(s): 島佐知子,飯島英樹,新崎信一郎,辻井正彦ら
  • Journal Title: 潰瘍 Volume: 38巻 1号 Pages: 58-63
  • NAID: 10028268520
• [Journal Article] GDP-mannose-4, 6-dehydratase (GMDS) deficiency renders colon cancer cells resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor- and CD95-mediated apoptosis by inhibiting complex II formation (2011)
  • Author(s): Moriwaki K., Shinzaki S., et al
  • Journal Title: J Biol Chem Volume: 286(50) Issue: 50 Pages: 43123-33
  • DOI: 10.1074/jbc.m111.262741
  • Peer Reviewed
• [Journal Article] Fucosylated haptoglobin is a novel type of cancer biomarker linked to the prognosis after an operation in colorectral cancer (2011)
  • Author(s): Takeda Y, Shinzaki S, Okudo K, Miyoshi E, et al
  • Journal Title: Cancer Volume: 1002 Issue: 12 Pages: 3036-3043
  • DOI: 10.1002/cncr.26490
  • Peer Reviewed
• [Journal Article] Overexpression of α 1.6-fucosyltransferase in hepatoma enhances expression of Golgi phosphoprotein 2 in a fucosylation-independent manner (2011)
  • Author(s): Kawammoto S, Moriwaki K, Miyoshi E, et al
  • Journal Title: International Journal of Oncology Volume: 39 Pages: 203-208
  • DOI: 10.3892/ijo.2011.1005
  • Peer Reviewed
• [Journal Article] Association of vitamin K deficiency with bone metabolism and clinical disease activity in inflammatory bowel disease (2011)
  • Author(s): Nakajima S., Shinzaki S., et al
  • Journal Title: Nutrition Volume: 27(10) Issue: 10 Pages: 1023-8
  • DOI: 10.1016/j.nut.2010.10.021
  • Peer Reviewed
• [Journal Article] Functional analysis of agalactosyl IgG in inflammatory bowel disease patients. (2011)
  • Author(s): Nakajima S.Shinzaki S.
  • Journal Title: Inflamm Bowel Dis. Volume: (in press)
  • NAID: 10028268520
  • Peer Reviewed
• [Journal Article] Comparative Analysis of the Effects of Anti-IL-6 Receptor mAb and Anti-TNF mAb Treatment on CD4+ T Cell Responses in Murine Colitis. (2011)
  • Author(s): Terabe F. Shinzaki S., et al.
  • Journal Title: Inflamm Bowel Dis. Volume: 17(2) Pages: 491-502
  • Peer Reviewed
• [Journal Article] Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis. (2010)
  • Author(s): Obata T. Shinzaki S., et al.
  • Journal Title: Proc Natl Acad Sci USA. Volume: 107(16) Pages: 7419-24
  • Peer Reviewed
• [Journal Article] Clinical application of a lectin-antibody ELISA to measure fucosylated haptoglobin in sera of patients with pancreatic cancer. (2010)
  • Author(s): Matsumoto H. Shinzaki S., et al.
  • Journal Title: Clin Chem Lab Med. Volume: 48(4) Pages: 505-12
  • Peer Reviewed
• [Journal Article] iTRAQ-based proteomic identification of leucine rich alpha 2 glycoprotein (LRG) as a novel inflammatory biomarker in autoimmune diseases. (2010)
  • Author(s): Serada S. Shinzaki S., et al.
  • Journal Title: Ann Rheum Dis. Volume: 69(4) Pages: 770-4
  • Peer Reviewed
• [Presentation] 消化器疾患における新規分子マーカー クローン病バイオマーカーとしての「ガラクトース欠損 IgG」Agal-IgG ELISA の開発と臨床応用に けた検討 (2013)
  • Author(s): 新崎 信一郎ら
  • Organizer: 第99回日本消化器病学会総会
  • Place of Presentation: 鹿児島
  • Year and Date: 2013-03-21
• [Presentation] Altered oligosaccharide structures reduce colitis induction in mice defective in glycosyltransferases (2013)
  • Author(s): Shinzaki S.
  • Organizer: 8th Congress of European Crohn's and Colitis Organization
  • Place of Presentation: オーストリア・ウイーン
• [Presentation] N-アセチルグルコサミン転移酵素 V (GnT -V)はマクロフ の機能不全を介して腸管炎症を増悪させる (2012)
  • Author(s): 石井真悠子ら
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-14
• [Presentation] ポリラクトサミンを介したB 細胞とマクロフ による腸炎保護作用 (2012)
  • Author(s): 藤井宏修ら
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-14
• [Presentation] Regulation of oligosaccharide-associated enzymes by TNF-alpha in B cells of Crohn's disease (2012)
  • Author(s): Shinzaki S., et al
  • Organizer: アメリカ消化器病学会週間2012
  • Place of Presentation: アメリカ・サンディエゴ
  • Year and Date: 2012-05-20
• [Presentation] Lectin-based immunoassay for aberrant IgG glycosylation as the biomarker for Crohn's disease (2012)
  • Author(s): Shinzaki S., et al
  • Organizer: アメリカ消化器病学会週間 2012
  • Place of Presentation: アメリカ・サンディエゴ
  • Year and Date: 2012-05-20
• [Presentation] Overexpression of Nacetylglucosaminyltransferase V (GnT -V) exacerbates murine colitis with dysfunction of macrophages (2012)
  • Author(s): Ishii M., et al
  • Organizer: アメリカ消化器病学会週間 2012
  • Place of Presentation: アメリカ・サンディエゴ
  • Year and Date: 2012-05-20
• [Presentation] Overexpression of N-acetylglucosaminyltransferase V (GnT-V) exacerbates murine colitis with dysfunction of macrophages (2012)
  • Author(s): Ishii M.
  • Organizer: アメリカ消化器病学会週間（DDW)
  • Place of Presentation: アメリカ・サンディエゴ
• [Presentation] Lectin-based immunoassay for aberrant IgG glycosylation as the biomarker for Crohn’s disease (2012)
  • Author(s): Shinzaki S.
  • Organizer: アメリカ消化器病学会週間（DDW)
  • Place of Presentation: アメリカ・サンディエゴ
• [Presentation] Regulation of oligosaccharide-associated enzymes by TNF-alpha in B cells of Crohn’s disease (2012)
  • Author(s): Tatsunaka N.
  • Organizer: アメリカ消化器病学会週間（DDW)
  • Place of Presentation: アメリカ・サンディエゴ
• [Presentation] N-アセチルグルコサミン転移酵素V（GnT-V）は、マクロファージの機能不全を介して腸管炎症を増悪させる (2012)
  • Author(s): 石井真悠子
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] ポリラクトサミンを介したＢ細胞とマクロファージによる腸炎抑制機構 (2012)
  • Author(s): 藤井宏修
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] クローン病患者B細胞におけるTNF-αを介したガラクトシル化の制御 (2011)
  • Author(s): 竜中法佳、新崎信一郎
  • Organizer: 日本臨床検査医学会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2011-11-19
• [Presentation] 双子研究から明らかになったIgGの糖鎖構造の遺伝性について (2011)
  • Author(s): 浅澤瞳美、新崎信一郎
  • Organizer: 日本臨床検査医学会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2011-11-19
• [Presentation] 双子研究から明らかになった IgG の糖鎖構造の遺伝性について (2011)
  • Author(s): 浅澤 瞳美ら
  • Organizer: 第58回日本臨床検査医学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2011-11-17
• [Presentation] 腸管炎症における N-アセチルグルコサミン転移酵素V(GnT -V)の役割 (2011)
  • Author(s): 石井 真悠子ら
  • Organizer: 第58回日本臨床検査医学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2011-11-17
• [Presentation] クローン病患者 B 細胞における TNF-αを介したガラクトシル化の制御 (2011)
  • Author(s): 竜 法佳ら
  • Organizer: 第58回日本臨床検査医学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2011-11-17
• [Presentation] ポリラクトサミンを介した B 細胞とマクロフ における腸炎保護作用 (2011)
  • Author(s): 藤井 宏修ら
  • Organizer: 第53回日本消化器病学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2011-10-20
• [Presentation] IgA 糖鎖構造に基づく炎症性腸疾患の診断と予後予測 (2011)
  • Author(s): 井上 隆弘ら
  • Organizer: 第53回日本消化器病学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2011-10-20
• [Presentation] 炎症性腸疾患におけるIgA O 結合型糖鎖異常の機序について (2011)
  • Author(s): 井上 隆弘ら
  • Organizer: 第97回日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-13
• [Presentation] Galectin-polylactosamine interaction between B cells and macrophages contributes to protect murine colitis defective in beta-1, 4-galactosyltransferase I (2011)
  • Author(s): Shinzaki S., et al
  • Organizer: DDW2011(アメリカ消化器病学会週間)
  • Place of Presentation: シカゴ(アメリカ合衆国)
  • Year and Date: 2011-05-08
• [Presentation] Galectinpolylactosamine interaction between B cells and macrophages contributes to protect murine colitis defective in beta-1,4-galactosyltransferase I (2011)
  • Author(s): Shinzaki S, et al
  • Organizer: アメリカ消化器病学会週間 2011
  • Place of Presentation: アメリカ・シカゴ
  • Year and Date: 2011-05-07
• [Presentation] インフリキシマブによる IgG 糖鎖や B 細胞に於ける糖鎖関連酵素の制御 (2011)
  • Author(s): 新崎 信一郎ら
  • Organizer: 第7回日本消化管学会総会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2011-02-18
• [Presentation] ガラクトース転移酵素の欠損は、実験的腸炎を軽減させる (2010)
  • Author(s): 新崎 信一郎ら
  • Organizer: 第83回日本生化学会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] 糖鎖関連バイオマーカーを用いたクローン病に対するインフリキシマブ治療戦略 (2010)
  • Author(s): 新崎 信一郎ら
  • Organizer: 第52回日本消化器病学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-13
• [Presentation] 糖鎖関連バイオマーカーを用いたクローン病に対するインフリキシマブ治療戦略 (2010)
  • Author(s): 新崎信一郎、飯島英樹、三善英知
  • Organizer: 第52回日本消化器病学会大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2010-10-13
• [Presentation] Protective role in deficiency of galactosyltransferase for murine colitis with upregulation of IL-10 by communication of B cells and macrophages (2010)
  • Author(s): Shinzaki S., et al.
  • Organizer: DDW2010(アメリカ消化器病学会週間)
  • Place of Presentation: ニューオーリンズ(アメリカ合衆国)
  • Year and Date: 2010-05-03
• [Presentation] ガラクトース転移酵素欠損マウスB細胞の腸炎保護作用 (2010)
  • Author(s): 新崎信一郎、飯島英樹、三善英知
  • Organizer: 第96回日本消化器病学会総会
  • Place of Presentation: 新潟コンベンションセンター
  • Year and Date: 2010-04-22
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/gh/
• [Remarks]
  • URL: http://sahswww.med.osaka-u.ac.jp/~tousa/index.html