Analysis of mechanisms for formation of pathogenic immune complexes and establishment of novel therapeutic approach in IgA nephropathy

• Project/Area Number: 22790802
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: Juntendo University
• Principal Investigator: SUZUKI Hitoshi 順天堂大学, 医学部, 助教 (10468572)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: IgA腎症 / 糖鎖異常IgA1 / 免疫複合体 / 粘膜免疫

Research Abstract

IgA nephropathy(IgAN), the most common glomerulonephritis, is characterized by mesangial IgA1-containing immunodeposits. Aberrant IgA1 and anti-glycan IgG are produced by activation of TLR9 and several cytokines. Serum levels of aberrant IgA1, anti-glycan IgG, and IgG-IgA immune complexes may be useful biomarkers for judgment of indication of tonsillectomy and efficacy of therapy.

Research Products

• [Journal Article] IgA分子の糖鎖異常と発症・進展における役割 (2012)
  • Author(s): 鈴木仁、富野康日己
  • Journal Title: 腎と透析 Volume: 72巻(in press)
• [Journal Article] The pathophysiology of IgA nephropathy (2011)
  • Author(s): Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB, Wyatt RJ, Scolari F, Mestecky J, Gharavi AG, Julian BA
  • Journal Title: J Am Soc Nephrol Volume: 22 Pages: 1795-1803
  • Peer Reviewed
• [Journal Article] Aberrant glycosylation of IgA1 and anti-glycan antibodies in IgA nephropathy : role of mucosal immune system (2011)
  • Author(s): Novak J, Moldoveanu Z, Julian BA, Raska M, Wyatt RJ, Suzuki Y, Tomino Y, Gharavi AG, Mestecky J, Suzuki H
  • Journal Title: Adv Otorhinolaryngol Volume: 72 Pages: 60-3
• [Journal Article] Reevaluation of the mucosa-bone marrow axis in IgA nephropathy with animal models (2011)
  • Author(s): Suzuki Y, Suzuki H, Sato D, Kajiyama T, Okazaki K, Hashimoto A, Kihara M, Yamaji K, Satake K, Nakata J, Aizawa M, Novak J, Tomino Y.
  • Journal Title: Adv Otorhinolaryngol Volume: 72 Pages: 64-7
  • Peer Reviewed
• [Journal Article] IgA1 immune complexes from pediatric patients with IgA nephropathy activate cultured human mesangial cells (2011)
  • Author(s): Novak J, Kafkova LR, Suzuki H, Tomana M, Matousovic K, Brown R, Stacy Hall, Sanders JT, Eison TM, Moldoveanu Z, Novak L, Novak Z, Mayne R, Julian BA, Mestecky J, Wyatt RJ
  • Journal Title: Nephrol Dial Transplant Volume: 26 Pages: 3451-3457
  • Peer Reviewed
• [Journal Article] Oxidative stress and galactose-deficient IgA1 as markers of progression in IgA nephropathy (2011)
  • Author(s): Camilla R, Suzuki H, Dapra V, Loiacono E, Peruzzi L, Amore A, Ghiggeri GM, Mazzucco G, Scolari F, Gharavi AG, Appel GB, Troyanov S, Novak J, Julian BA, Coppo R
  • Journal Title: Clin J Am Soc Nephrol Volume: 6 Pages: 1903-11
  • Peer Reviewed
• [Journal Article] Pathological role of tonsillar B cells in IgA nephropathy (2011)
  • Author(s): Suzuki Y, Suzuki H, Nakata J, Sato D, Kajiyama T, Watanabe T, Tomino Y
  • Journal Title: Clinical and Developmental Immunology
  • Peer Reviewed
• [Journal Article] Different pathological roles of Toll-like receptor 9 on mucosal B cells and dendritic cells in murine IgA nephropathy (2011)
  • Author(s): Kajiyama T, Suzuki Y, Kihara M, Suzuki H, Horikoshi S, Tomino Y
  • Journal Title: Clinical and Developmental Immunology
  • Peer Reviewed
• [Journal Article] Aberrant Glycosylation of IgA1 is Inherited in Pediatric IgA Nephropathy and Henoch-Schonlein Purpura Nephritis (2011)
  • Author(s): Kiryluk K, Moldoveanu Z, Sanders JT, Elison TM, Suzuki H, Julian BA, Novak J, Gharavi AG, Wyatt RJ
  • Journal Title: Kidney Int Volume: 80 Pages: 79-87
  • Peer Reviewed
• [Journal Article] 糖鎖異常IgA1 (2011)
  • Author(s): 鈴木仁、富野康日己
  • Journal Title: IgA腎症診療マニュアル Pages: 11-17
• [Journal Article] IgA腎症の成因 (2011)
  • Author(s): 鈴木仁、富野康日己
  • Journal Title: Annual Review腎臓 Pages: 21-29
• [Journal Article] IgA腎症の発症、扁桃病巣感染、粘膜免疫 (2011)
  • Author(s): 鈴木仁
  • Journal Title: IgA腎症診療ガイドQ & A進行性腎障害診療指針シリーズ Pages: 34-35
• [Journal Article] Reevaluation of the mucosa-bone marrow axis in IgA nephropathy with animal models (2011)
  • Author(s): Suzuki Y, Suzuki H, et al
  • Journal Title: Adv Otorhinolaryngol Volume: 72 Pages: 64-67
  • DOI: 10.1159/000324608
  • ISBN: 9783805597227, 9783805597234
• [Journal Article] Aberrant glycosylation of IgA1 and anti-glycan antibodies in IgA nephropathy : role of mucosal immune system (2011)
  • Author(s): Novak J, Moldoveanu Z, Julian BA, Raska M, et al
  • Journal Title: Adv Otorhinolaryngol Volume: 72 Pages: 60-63
  • DOI: 10.1159/000324607
  • ISBN: 9783805597227, 9783805597234
• [Journal Article] Oxidative stress and galactose-deficient IgA1 as markers of progression in IgA nephropathy (2011)
  • Author(s): Camilla R, Suzuki H, et al
  • Journal Title: Clin J Am Soc Nephrol Volume: 6 Issue: 8 Pages: 1903-1911
  • DOI: 10.2215/cjn.11571210
  • Peer Reviewed
• [Journal Article] Pathological role of tonsillar B cells in IgA nephropathy (2011)
  • Author(s): Suzuki Y, Suzuki H, et al
  • Journal Title: Clinical and Developmental Immunology Volume: (In press) Pages: 1-8
  • DOI: 10.1155/2011/639074
  • Peer Reviewed
• [Journal Article] Different pathological roles of Toll-like receptor 9 on mucosal Bcells and dendritic cells in murine IgA nephropathy (2011)
  • Author(s): Kajiyama T, Suzuki Y, Kihara M, Suzuki H, et al
  • Journal Title: Clinical and Developmental Immunology Volume: (In press) Pages: 1-10
  • DOI: 10.1155/2011/819646
  • Peer Reviewed
• [Journal Article] IgA腎症の発症、扁桃病巣感染、粘膜免疫 (2011)
  • Author(s): 鈴木仁
  • Journal Title: IgA腎症診療ガイドQ&A進行性腎障害診療指針シリーズ Pages: 34-35
• [Journal Article] Galactosylation of serum IgA1 O-glycan in celiac disease (2010)
  • Author(s): Lindfors K, Suzuki H, Novak J, Collin P, Saavalainen P, Koskinen L, Maki M, Kaukinen K
  • Journal Title: J Clin Immunol Volume: 31 Pages: 74-79
  • Peer Reviewed
• [Journal Article] Clustered O-glycans of IgA1 : Defining macro-and micro-heterogeneity by use of electron capture/transfer dissociation (2010)
  • Author(s): Takahashi K, Wall SB, Suzuki H, Smith AD, Hall S, Paulsen K, Kilian M, Mobley JA, Julian BA, Mestecky J, Novak J, Renfrow MB
  • Journal Title: Mol Cell Proteomics Volume: 9 Pages: 2545-2557
  • Peer Reviewed
• [Journal Article] Recognition of Galactose-Deficient O-Glycans in the Hinge Region of IgA1 by N-Acetylgalactosamine-Specific Snail Lectins : A Comparative Binding Study (2010)
  • Author(s): Gomes MM, Suzuki H, Brooks MT, Tomana M, Moldoveanu Z, Mestecky J, Julian BA, Novak J, Herr AB
  • Journal Title: Biochemistry Volume: 13 Pages: 5671-5682
  • Peer Reviewed
• [Journal Article] IgA腎症における糖鎖異常IgA1と免疫複合体の病的意義 (2010)
  • Author(s): 鈴木仁
  • Journal Title: 医学のあゆみ Volume: 232巻 Pages: 1107-1112
• [Journal Article] IgA腎症における糖鎖異常 (2010)
  • Author(s): 鈴木仁
  • Journal Title: 臨床内科 Volume: 106巻 Pages: 98-101
• [Journal Article] Recognition of Galactose-Deficient O-Glycans in the Hinge Region of IgA1 by N-Acetylgalactosamine-Specific Snail Lectins (2010)
  • Author(s): Suzuki H
  • Journal Title: Biochemistry Volume: 13 Pages: 5671-5682
  • Peer Reviewed
• [Presentation] Novel diagnostic approach for IgA nephropathy (2011)
  • Author(s): Yanagawa H, Suzuki H, et al
  • Organizer: The ASN (American Society of Nephrology) 44^<th> Annual Meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2011-11-11
• [Presentation] Characterization of Galactose-deficient IgA1 Secreted by IgA1-producing Cell Lines : Implication for Pathogenesis of IgA Nephropathy (2011)
  • Author(s): Takahashi K, Suzuki H, et al
  • Organizer: The ASN (American Society of Nephrology) 44^<th> Annual Meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2011-11-11
• [Presentation] Effect of gp130 Cytokines on IgA1-producing Cells from Patients with IgA Nephropathy (2011)
  • Author(s): Yamada K, Raska M, Moldoveanu Z, Suzuki H, et al
  • Organizer: The ASN (American Society of Nephrology) 44^<th> Annual Meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2011-11-11
• [Presentation] Role of N-acetylgalactosaminyl Transferases in the Synthesis of Aberrant IgA1 O-glycans in IgA Nephropathy (2011)
  • Author(s): Raska M, Yamada K, Horynova M, Takahashi K, Suzuki H, et al
  • Organizer: The ASN (American Society of Nephrology) 44^<th> Annual Meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2011-11-11
• [Presentation] Evaluation of Serial Serum Levels of IgA-IgG Immune Complexes Prior To Diagnosis of IgA Nephropathy (2011)
  • Author(s): Olson SW, Suzuki H, et al
  • Organizer: The ASN (American Society of Nephrology) 44^<th> Annual Meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2011-11-11
• [Presentation] Novel noninvasive biomarkers for disease activity of IgA nephropathy (2011)
  • Author(s): Suzuki Y, Matsuzaki K, Suzuki H, et al
  • Organizer: The ASN (American Society of Nephrology) 44^<th> Annual Meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2011-11-10
• [Presentation] Evaluation of Serial Serum Levels of IgA-IgG Immune Complexes Prior To Diagnosis of IgA Nephropathy (2011)
  • Author(s): Olson SW, Suzuki H
  • Organizer: The ASN(American Society of Nephrology) 44^<th> Annual Meeting
  • Place of Presentation: Philadelphia, USA
• [Presentation] Role of N-acetylgalactosaminyl Transferases in the Synthesis of Aberrant IgA1 O-glycans in IgA Nephropathy (2011)
  • Author(s): Raska M, Yamada K, Horynova M, Takahashi K, Suzuki H
  • Organizer: The ASN(American Society of Nephrology) 44^<th> Annual Meeting
  • Place of Presentation: Philadelphia, USA
• [Presentation] Novel noninvasive biomarkers for disease activity of IgA nephropathy (2011)
  • Author(s): Suzuki Y, Matsuzaki K, Suzuki H
  • Organizer: The ASN(American Society of Nephrology) 44^<th> Annual Meeting
  • Place of Presentation: Philadelphia, USA
• [Presentation] Effect of gp130 Cytokines on IgA1-producing Cells from Patients with IgA Nephropathy (2011)
  • Author(s): Yamada K, Raska M, Moldoveanu Z, Suzuki H
  • Organizer: The ASN(American Society of Nephrology) 44^<th> Annual Meeting
  • Place of Presentation: Philadelphia, USA
• [Presentation] Characterization of Galactose-deficient IgA1 Secreted by IgA1-producing Cell Lines : Implication for Pathogenesis of IgA Nephropathy (2011)
  • Author(s): Takahashi K, Suzuki H
  • Organizer: The ASN(American Society of Nephrology) 44^<th> Annual Meeting
  • Place of Presentation: Philadelphia, USA
• [Presentation] Novel diagnostic approach for IgA nephropathy (2011)
  • Author(s): Yanagawa H, Suzuki H
  • Organizer: The ASN(American Society of Nephrology) 44^<th> Annual Meeting.
  • Place of Presentation: Philadelphia, USA
• [Presentation] Glycosylation pathways of O-glycans in the hinge region of monomeric and polymeric circulatory IgA1 (2011)
  • Author(s): Novak J, Suzuki H
  • Organizer: 15^<th> International Congress of Mucosal Immunology
  • Place of Presentation: Paris, France
• [Presentation] Pathways of aberrant O-glycosylation of IgA1 in IgA nephropathy (2011)
  • Author(s): Novak J, Suzuki H
  • Organizer: Annual meeting of European Renal Association-European Dialysis and Transplant Association
  • Place of Presentation: Prague, Czech Republic
• [Presentation] IgA腎症患者のTLR9遺伝子の一塩基多型と重症度の検討 (2011)
  • Author(s): 松崎慶一、鈴木祐介、鈴木仁, ほか
  • Organizer: 日本腎臓学会
  • Place of Presentation: 横浜
• [Presentation] Glycosylation pathways of O-glycans in the hinge region of monomeric and polymeric circulatory IgA1 (2011)
  • Author(s): Novak J, Suzuki H, et al
  • Organizer: 15^<th> international Congress of Mucosal Immunology
  • Place of Presentation: Paris, France
• [Presentation] The role of tonsillar B cells in the pathogenesis of IgA nephropathy (2010)
  • Author(s): 鈴木仁
  • Organizer: 国際扁桃粘膜免疫学会
  • Place of Presentation: 旭川