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2016 Fiscal Year Annual Research Report

The study on the effect of tonsillectomy combined with steroid pulse therapy against IgA nephropathy

Research Project

Project/Area Number 26460449
Research InstitutionTohoku University

Principal Investigator

城 謙輔  東北大学, 医学系研究科, 客員教授 (10057086)

Co-Investigator(Kenkyū-buntansha) 中村 保宏  東北大学, 医学系研究科, 大学院非常勤講師 (80396499)
Project Period (FY) 2014-04-01 – 2017-03-31
KeywordsIgA腎症 / 扁桃炎 / 樹状細胞 / 定量RTーPCR / T細胞 / B細胞
Outline of Annual Research Achievements

IgA腎症の扁桃炎と腎糸球体病変との連関に関する分子病理学的研究
扁桃に由来し、糸球体病変を惹起する諸因子の扁桃内での分子発現を、これまでの成果を参考に分子生物学的手法を用いてIgA腎症患者の扁桃を検討した。凍結したIgA腎症患者の扁桃(5検体)と慢性扁桃炎の扁桃(4検体)のTotal RNAを定量RT-PCR法にて増幅し、Human Genome U133 Plus 2.0 Array(Affymetrix,Inc)によるトランスクリプトーム解析(38,500遺伝子)を行った。その結果、対照群に用いた慢性扁桃炎の扁桃に対し、IgA腎症患者の扁桃で異なるRNA発現パターンを示す遺伝子は、Cancer関連やリンパ腫関連などの17個の遺伝子に絞られた。また、これまでの研究から、腎糸球体の急性活動性病変に相関する扁桃病変としてT細胞結節の増加とその中心のCD208陽性の樹状細胞LAMP-3の発現が相関し、一方、慢性病変である分節性硬化病変は、扁桃陰窩上皮の網状化阻害の程度に相関した。そのため、扁桃のT細胞結節数の増加と陰窩上皮の網状化阻害の二極化に関与する遺伝子を検索したところ、167個の遺伝子が同定された。
共同研究の成果として、IgA腎症患者扁桃の慢性刺激に伴うToll-Like Receptor 9が、扁桃におけるリンパ濾胞明中心のB 細胞 を介して TNF family member a proliferation-inducing ligand (APRIL)の過剰産生を誘導して、糖鎖不全IgA1の過剰産生に関与した(Muto M et al. JASN 2017)。さらに、担IgA形質細胞の増加によるIgA産生能(IgA class switching)を促進する因子として、リンパ濾胞の樹状細胞に発現するthymic stromal lymphopoietin (TSLP)が関与した(Meng H, et al. Transl Res. 2016)。今回の定量RT-PCR法を用いたトランスクリプトーム解析により確認された遺伝子群とIgA産生亢進に関与する分子との関連も解析する予定である。

  • Research Products

    (14 results)

All 2017 2016

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 10 results,  Acknowledgement Compliant: 5 results) Presentation (3 results) (of which Int'l Joint Research: 3 results) Book (1 results)

  • [Journal Article] Toll-Like Receptor 9 Stimulation Induces Aberrant Expression of a Proliferation-Inducing Ligand by Tonsillar Germinal Center B Cells in IgA Nephropathy.2017

    • Author(s)
      Muto M, Manfroi B, Suzuki H, Joh K, Nagai M, Wakai S, Righini C, Maiguma M, Izui S, Tomino Y, Huard B, Suzuki Y.
    • Journal Title

      J Am Soc Nephrol

      Volume: 28 Pages: 1227-1238

    • DOI

      10.1681/ASN.2016050496

    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Evidence from the Oxford Classification cohort supports the clinical value of subclassification of focal segmental glomerulosclerosis in IgA nephropathy.2017

    • Author(s)
      Bellur SS, Lepeytre F, Vorobyeva O, Troyanov S, Cook HT, Roberts IS, Alpers CE, Jennette JC, Joh K, et al.
    • Journal Title

      Kidney Int

      Volume: 91 Pages: 235-243

    • DOI

      10.1016/j.kint.2016.09.029

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Treatment of pediatric-onset lupus nephritis: a proposal of optimal therapy.2017

    • Author(s)
      Tanaka H, Joh K, Imaizumi T.
    • Journal Title

      Clin Exp Nephrol

      Volume: - Pages: -

    • DOI

      10.1007/s10157-017-1381-1

    • Peer Reviewed / Open Access
  • [Journal Article] Power Doppler Ultrasonography for Detection of Increased Vascularity in the Fascia:A Potential Early Diagnostic Tool in Fasciitis of Dermatomyositis.2016

    • Author(s)
      Yoshida K, Nishioka M, Matsushima S, Joh K, Oto Y, Yoshiga M, Otani K, Ito H, Hirai K, Furuya K, Ukichi T, Noda K, Kingetsu I, Kurosaka D.
    • Journal Title

      Arthritis Rheumatol

      Volume: 68 Pages: 2986-2991.

    • DOI

      10.1002/art.39798

    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Thymic stromal lymphopoietin in tonsillar follicular dendritic cells correlates2016

    • Author(s)
      Meng H, Li H, Ohe R, Naing YA, Yang S, Kabasawa T, Kato T, Osakabe M, Ohtake H, Ishida A, Lu J, Zhang L, Ohta N, Kakehata S, Joh K, Shi Q, Jin X, Geng J, Yamakawa M.
    • Journal Title

      Transl Res

      Volume: 176 Pages: 1-17

    • DOI

      10.1016/j.trsl.2016.04.008

    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Does Dent disease remain an underrecognized cause for young boys with focal glomerulosclerosis?2016

    • Author(s)
      Kubo K, Aizawa T, Watanabe S, Tsugawa K, Tsuruga K, Ito E, Joh K, Tanaka H.
    • Journal Title

      Pediatr Int

      Volume: 58 Pages: 747-749

    • DOI

      10.1111/ped.12944

    • Peer Reviewed / Open Access
  • [Journal Article] Reproducibility for pathological prognostic parameters of the Oxford classification of IgA nephropathy: a Japanese cohort study of the Ministry of Health, Labor and Welfare.2016

    • Author(s)
      Hisano S, Joh K, Katafuchi R, Shimizu A, Hashiguchi N, Kawamura T, Matsuo S.
    • Journal Title

      Clin Exp Nephrol

      Volume: 21 Pages: 92-96

    • DOI

      10.1007/s10157-016-1258-8

    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Rapid specimen preparation to improve the throughput of electron microscopic2016

    • Author(s)
      Thai TQ, Nguyen HB, Saitoh S, Wu B, Saitoh Y, Shimo S, Elewa YH, Ichii O, Kon Y, Takaki T, Joh K, Ohno N.
    • Journal Title

      Med Mol Morphol

      Volume: 49 Pages: 154-162

    • DOI

      10.1007/s00795-016-0134-7

    • Peer Reviewed / Open Access
  • [Journal Article] Interferon-Stimulated Gene 15, a Type I Interferon-Dependent Transcript, Is Involved in a Negative Feedback Loop in Innate Immune Reactions in Human Mesangial Cells.2016

    • Author(s)
      Imaizumi T, Shimada T, Matsumiya T, Yoshida H, Watanabe S, Tsuruga K, Kawaguchi S, Murakami M, Joh K, Tanaka H.
    • Journal Title

      Nephron

      Volume: 132 Pages: 144-52

    • DOI

      10.1159/000443934

    • Peer Reviewed / Open Access
  • [Journal Article] Pathological sub-analysis of a multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy versus steroid pulse monotherapy in patients with immunoglobulin A nephropathy.2016

    • Author(s)
      Katafuchi R, Kawamura T, Joh K, Hashiguchi A, Hisano S, Shimizu A, Miyazaki Y, Nagata M, Matsuo S.
    • Journal Title

      Clin Exp Nephrol

      Volume: 20 Pages: 244-252

    • DOI

      10.1007/s10157-015-1159-2

    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Potassium chloride in hypoelectrolytic isoosmotic solution for infusion prevents an artifact of electron microscopic morphology for fresh renal biopsy specimen2016

    • Author(s)
      Takaki T, Nakamura Y, Sato N, Joh K
    • Organizer
      Kidney Week 2016
    • Place of Presentation
      Chicago, USA.
    • Year and Date
      2016-11-15 – 2016-11-20
    • Int'l Joint Research
  • [Presentation] Pathology of lupus nephritis and antiphospholipid syndrome in renal biopsy. UPTODATE; Leiden Consensus Meeting2016

    • Author(s)
      Joh K
    • Organizer
      5th Heilongjiang International Forum on Renal Pathology and Kidney Research Progress
    • Place of Presentation
      Harbin, China
    • Year and Date
      2016-08-05 – 2016-08-06
    • Int'l Joint Research
  • [Presentation] Histological Classification of IgA nephropathy;2016

    • Author(s)
      Joh K
    • Organizer
      The 36th Annual Meeting of the Korean Society of Nephrology
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2016-06-02 – 2016-06-05
    • Int'l Joint Research
  • [Book] 腎生検電顕アトラス2016

    • Author(s)
      城 謙輔
    • Total Pages
      1-219
    • Publisher
      南山堂、東京

URL: 

Published: 2018-01-16  

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