Development of biomarker for IgAN: Development of biomarker for IgAN: An international collaboration study

• Project/Area Number: 15H05292
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Kidney internal medicine
• Research Institution: Fujita Health University
• Principal Investigator: Yuzawa Yukio 藤田保健衛生大学, 医学部, 教授 (00191479)
• Co-Investigator(Kenkyū-buntansha): 比企 能之 藤田保健衛生大学, 医学部, 教授 (20156566) ; 秋山 真一 名古屋大学, 医学系研究科, 特任講師 (20500010) ; 長谷川 みどり 藤田保健衛生大学, 医学部, 教授 (40298518) ; 高橋 和男 藤田保健衛生大学, 医学部, 講師 (90631391)
• Research Collaborator: Jan Novak University of Alabama at Birmingham, 教授 ; Renfrow Matthew B. University of Alabama at Birmingham, 准教授 ; Francesco Paolo Schena University of Bari, 教授
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2015: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: IgA腎症 / 糖鎖異常IgA / バイオマーカー開発 / 国際間共同研究 / 糖鎖医学 / 人種差 / 翻訳後修飾解析 / バイオマーカー / 糖鎖 / 質量分析 / O結合型糖鎖 / 翻訳後修飾 / 国際間研究

Outline of Final Research Achievements

IgA1 with galactose (Gal)-deficient hinge-region (HR) O-glycans (Gd-IgA1) plays a key role in the pathogenesis of IgA nephropathy (IgAN). To identify potentially disease-specific IgA1 HR O-glycoforms, we profiled serum IgA1 HR glycopeptides using specimens from Japanese IgAN patients and healthy controls (HC) of different races. IgA1 from sera of 20 Japanese IgAN patients and 50 HC, recruited from Caucasian, Black, Hispanic, Asian, and Japanese populations, was purified by affinity chromatography. IgA1 HR glycosylation heterogeneity including glycan attachment sites were analyzed by liquid chromatography-high-resolution mass spectrometry. We successfully characterized HR O-glycan profile in normal subjects and identified the O-glycoforms correlating with serum level of Gd-IgA1. Identification of specific HR O-glycoforms increasing in IgAN patients will lead to the development of robust biomarker in IgAN.

Research Products

• [Int'l Joint Research] University of Alabama at Birmingham(米国)
• [Int'l Joint Research] University of Bari(Italy)
• [Journal Article] A Multicenter Study of the Predictive Value of Crescents in IgA Nephropathy. (2017)
  • Author(s): Haas M, Verhave JC, Liu ZH, Alpers CE, Barratt J, Becker JU, Cattran D, Cook HT, Coppo R, Feehally J, Pani A, Perkowska-Ptasinska A, Roberts IS, Soares MF, Trimarchi H, Wang S, Yuzawa Y, Zhang H, Troyanov S, Katafuchi R.
  • Journal Title: J Am Soc Nephrol. Volume: 28(2) Issue: 2 Pages: 691-701
  • DOI: 10.1681/asn.2016040433
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Evidence-based clinical practice guidelines for IgA nephropathy 2014. (2016)
  • Author(s): Yuzawa Y, Yamamoto R, Takahashi K, Katafuchi R, Tomita M, Fujigaki Y, Kitamura H, Goto M, Yasuda T, Sato M, Urushihara M, Kondo S, Kagami S, Yasuda Y, Komatsu H, Takahara M, Harabuchi Y, Kimura K, Matsuo S.
  • Journal Title: Clin Exp Nephrol. Volume: 20 Issue: 4 Pages: 511-35
  • DOI: 10.1007/s10157-015-1223-y
  • Peer Reviewed / Open Access
• [Journal Article] The Level of IgA Antibodies to Endothelial Cells Correlates with Histological Evidence of Disease Activity in Patients with Lupus Nephritis. (2016)
  • Author(s): Kondo A, Takahashi K, Mizuno T, Kato A, Hirano D, Yamamoto N, Hayashi H, Koide S, Takahashi H, Hasegawa M, Hiki Y, Yoshida S, Miura K, Yuzawa Y.
  • Journal Title: PLoS One Volume: 11 Issue: 10 Pages: e0163085-e0163085
  • DOI: 10.1371/journal.pone.0163085
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] In a retrospective international study, circulating miR-148b and let-7b were found to be serum markers for detecting (2016)
  • Author(s): Serino G, Pesce F, Sallustio F, De Palma G, Cox SN, Curci C, Zaza G, Lai KN, Leung JC, Tang SC, Papagianni A
  • Journal Title: Kidney Int. Volume: 89(3) Issue: 3 Pages: 683-692
  • DOI: 10.1038/ki.2015.333
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] New Insights into the Pathogenesis of IgA Nephropathy. (2015)
  • Author(s): Novak J, Rizk D, Takahashi K, Zhang X, Bian Q, Ueda H, Ueda Y, Reily C, Lai LY, Hao C, Novak L, Huang ZQ, Renfrow MB, Suzuki H, Julian BA
  • Journal Title: Kidney Dis (Basel) Volume: 1(1) Pages: 8-18
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Analysis of IgA1 hinge-region O-glycoforms of multiracial healthy subjects by mass spectrometry. (2018)
  • Author(s): Yukako Ohyama, Kazuo Takahashi, Shoko Matsushita, Hisateru Yamaguchi, Kazuki Nakajima, Tomohiro Mizuno, Hiroki Hayashi, Shigehisa Koide, Daijo Inaguma, Midori Hasegawa, Matthew B. Renfrow, Jan Novak, Yoshiyuki Hiki, Yukio Yuzawa
  • Organizer: ISN Frontiers 2018
  • Int'l Joint Research
• [Presentation] Racial Comparison of IgA1 Hinge-Region O-Glycoforms by High-Resolution Mass Spectrometry (2017)
  • Author(s): Yukako Ohyama, Kazuo Takahashi, Shoko Matsushita, Hisateru Yamaguchi, Kazuki Nakajima, Tomohiro Mizuno,4 Hiroki Hayashi, Shigehisa Koide, Daijo Inaguma, Midori Hasegawa, Jan Novak,5 Yoshiyuki Hiki, Yukio Yuzawa.
  • Organizer: Kidney Week 2017 (ASN)
  • Int'l Joint Research
• [Presentation] 正常人IgA1 O結合型糖鎖構造の人種間比較 (2017)
  • Author(s): 大山 友香子, 高橋 和男, 山口 央輝, 松下 祥子, 加藤 彰浩, 吉田 祐理, 水野 智博, 深町 幸宏, 横井 靖人, 中嶋 和紀, 比企 能之, 湯澤 由紀夫
  • Organizer: 第42回日本医用マススペクトル学会年会
• [Presentation] 糖鎖異常IgA1とIgA腎症 (2017)
  • Author(s): 高橋 和男, 大山 友香子, 山口 央輝, 松下 祥子, 中嶋 和紀, 比企 能之, Matthew B. Renfrow, Jan Novak, 湯澤 由紀夫
  • Organizer: 第14回「若手の力」フォーラム
• [Presentation] Comprehensive Analysis of IgA1 Hinge-Region O-Glycoforms in Patients with IgA Nephropathy (2016)
  • Author(s): Kazuo Takahashi, Hisateru Yamaguchi, Yukako Ohyama, Akihiro Kato, Tomohiro Mizuno, Yoshiyuki Hiki, Matthew B. Renfrow, Jan Novak, Yukio Yuzawa.
  • Organizer: Kidney Week 2016
  • Place of Presentation: McCormick Place in Chicago, IL, USA
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] Elucidation of the Roles of Tissue Transglutaminase in Mesangial Proliferative Glomerulonephritis. (2016)
  • Author(s): Kato A, Mizuno T, Takahashi K, Yoshida Y, Tatsukawa H, Mizuno M, Hitomi K, Yuzawa Y.
  • Organizer: Kidney Week 2016
  • Place of Presentation: McCormick Place in Chicago, IL, USA
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] Mesangial Tissue Transglutaminase Activity in Patients with IgA Nephropathy: Implications for the Pathogenesis (2016)
  • Author(s): Takahashi K, Mizuno T, Onouchi T, Yoshida Y, Ohyama Y, Akiyama S, Tatsukawa H, Hiki Y, Kusaka M, Nagamatsu T, Tsutsumi Y, Maruyama S, Kitamura H, Novak J, Hitomi K, Yuzawa Y.
  • Organizer: International IgA Nephropathy Symposium
  • Place of Presentation: Tours, France
  • Year and Date: 2016-09-15
  • Int'l Joint Research
• [Presentation] Comprehensive analysis of IgA1 hinge-region O-glycoforms by a sequential deglycosylation protocol (2016)
  • Author(s): Takahashi K, Yamaguchi H, Ohyama Y, Kato A, Yoshida Y, Mizuno T, Hiki Y, Renfrow MB, Novak J, Yuzawa Y.
  • Organizer: International IgA Nephropathy Symposium
  • Place of Presentation: Tours, France
  • Year and Date: 2016-09-15
  • Int'l Joint Research
• [Presentation] 質量分析によるIgA1ヒンジ部糖鎖異常部位の定量及び同定 (2016)
  • Author(s): 高橋和男、加藤彰浩、比企能之、吉田祐理、水野智博、山口央輝、林宏樹、小出滋久、長谷川みどり、RenfrowMatthewB.、NovakJan、湯澤由紀夫
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜会議センター, 神奈川県横浜市
  • Year and Date: 2016-06-17
• [Presentation] Detection of Mesangial Tissue Transglutaminase Activity in Human Kidney Biopsy Specimens. (2015)
  • Author(s): Kazuo Takahashi, Tomohiro Mizuno, Takanori Onouchi, Shin’ichi Akiyama, Hideki Tatsukawa, Mamoru Kusaka, Tadashi Nagamatsu, Yutaka Tsutsumi, Shoichi Maruyama, Hiroshi Kitamura, Jan Novak, Kiyotaka Hitomi, Yukio Yuzawa.
  • Organizer: Kidney Week 2015 (ASN)
  • Place of Presentation: San Diego, CA, USA. (San Diego Convention Center)
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] Expression of Mesangial Tissue Transglutaminase Is Independent of Aberrantly Glycosylated IgA in Patients with IgA Nephropathy. (2015)
  • Author(s): Akihiro Kato, Kazuo Takahashi, Tomohiro Mizuno, Stacy D. Hall, Yoshiyuki Hiki, Kiyotaka Hitomi, Jan Novak, Yukio Yuzawa.
  • Organizer: Kidney Week 2015 (ASN)
  • Place of Presentation: San Diego, CA, USA. (San Diego Convention Center)
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] 総会長主導企画1：IgA腎症の診断と治療のUP TO DATE 2. Oxford分類改訂の方向性とポイント (2015)
  • Author(s): 湯澤由紀夫
  • Organizer: 第58回日本腎臓学会学術大会
  • Place of Presentation: 名古屋市、名古屋国際会議場
  • Year and Date: 2015-06-07
  • Invited
• [Presentation] IgA腎症のメサンギウム組織トランスグルタミナーゼ活性は糖鎖異常IgA1と独立して疾患活動性と関連する (2015)
  • Author(s): 高橋 和男, 水野 智博, 尾之内 高慶, 秋山 真一, 林 宏樹, 小出 滋久, 佐藤 和一, 長谷川 みどり, 日下 守, 永松 正, 堤 寛, 丸山 彰一, 比企 能之, 北村 博司, 人見 清隆, 湯澤 由紀夫
  • Organizer: 第58回日本腎臓学会学術大会
  • Place of Presentation: 名古屋市、名古屋国際会議場
  • Year and Date: 2015-06-07
• [Presentation] IgA腎症の血清IgA1ヒンジ部O結合型糖鎖の詳細な解析 (2015)
  • Author(s): 高橋 和男, 近藤 亜矢子, 水野 智博, 秋山 真一, 林 宏樹, 小出 滋久, 佐藤 和一, 長谷川 みどり, 比企 能之, 湯澤 由紀夫
  • Organizer: 第58回日本腎臓学会学術大会
  • Place of Presentation: 名古屋市、名古屋国際会議場
  • Year and Date: 2015-06-07
• [Presentation] IgA腎症における組織トランスグルタミナーゼ活性の検出 (2015)
  • Author(s): 高橋 和男, 水野 智博, 尾之内 高慶, 秋山 真一, 日下 守, 永松 正, 堤 寛, 丸山 彰一, 比企 能之, 北村 博司, 人見 清隆, 湯澤 由紀夫
  • Organizer: 第52回日本臨床分子医学会学術集会
  • Place of Presentation: 京都府京都市、みやこめっせ
  • Year and Date: 2015-04-10
• [Book] Pathogenesis and Treatment in IgA Nephropathy (2016)
  • Author(s): Kazuo Takahashi, Ryohei Yamamoto, Yukio Yuzawa
  • Total Pages: 11
  • Publisher: Springer
• [Remarks] 藤田保健衛生大学医学部腎内科学IgA腎症研究グループ
  • URL: http://fujita-jin.blogat.jp/blog/2013/02/iga-f52d.html