Proteomics analysis in IgG4-related disease

• Project/Area Number: 15K09537
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kanazawa Medical University
• Principal Investigator: KAWANAMI Takafumi 金沢医科大学, 医学部, 講師 (20350762)
• Co-Investigator(Kenkyū-buntansha): 岩男 悠 金沢医科大学, 医学部, 助教 (10612244) ; 正木 康史 金沢医科大学, 医学部, 教授 (40238895)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: IgG4関連疾患 / プロテオミクス / クラススイッチ / Alpha-1 antitrypsin / LRA2G / IgG4 related disease / 2D-DIGE

Outline of Final Research Achievements

To understand the etiology/pathology of IgG4-related disease and its mechanism, we analyzed the proteins whose expression vary depending on the disease and its treatment using a proteomics approach. The proteins whose expressions are significantly different between before and after treatment and between healthy individuals and the patients were identified and validated by ELISA. In the serum before the treatment of IgG4-related disease, we observed the increases in IgG1, IgG4, Ig lambda, Ig kappa, as well as those in inflammatory factors such as α-1 antitrypsin (A1AT), apolipoprotein-L1, complement 4, C1q, and serum amyloid A protein precursor and those associated with the regulation of immune systems such as clusterin and Leucin-rich-α-2-glycoprotein (LRA2G).

Academic Significance and Societal Importance of the Research Achievements

IgG4関連疾患において特異的に変動するタンパク質群の網羅解析を行い、病態への関与が類推されるいくつかの因子を見いだした。IgG4関連疾患は、IgG4陽性細胞の増加や浸潤を特徴とするが、なぜIgG4が高いのか、原因なのか、結果なのかは未だ不明である。本研究により、IgG4関連疾患の病態に関わる機能分子や、タンパク質間の相互関係解析が進めば、IgG4関連疾患の病態形成のメカニズムに新たな知見が得られるとともに、その治療戦略への足がかりを掴む一歩になるものと考えている。

Research Products

• [Journal Article] Natural History and Predictors of Progression to Sjogren's Syndrome Among Participants of the Sj?gren's International Collaborative Clinical Alliance Registry (2018)
  • Author(s): Shiboski Caroline H.、Baer Alan N.、Shiboski Stephen C.、the Sjogren's International Collaborative Clinical Alliance Research Groups, et al.
  • Journal Title: Arthritis Care & Research Volume: 70 Issue: 2 Pages: 284-294
  • DOI: 10.1002/acr.23264
  • Peer Reviewed / Open Access
• [Journal Article] Sjogren’s syndrome manifesting as clinicopathological features of TAFRO syndrome: A case report. (2017)
  • Author(s): Fujimoto S, Kawabata H, Kurose N, Kawanami-Iwao H, Sakai T, Kawanami T, Fujita Y, Fukushima T, Masaki Y.
  • Journal Title: Medicine (Baltimore) Volume: 96(50) Issue: 50 Pages: e9220-e9220
  • DOI: 10.1097/md.0000000000009220
  • Peer Reviewed / Open Access
• [Journal Article] IgG4関連疾患のプロテオーム解析 (2017)
  • Author(s): 河南崇典、河南（岩男）悠、正木康史
  • Journal Title: 臨床免疫・アレルギー科 Volume: 67(4) Pages: 343-348
  • Peer Reviewed
• [Journal Article] A multicenter phase II prospective clinical trial of glucocorticoid for patients with untreated IgG4-related disease. (2016)
  • Author(s): Masaki Y, Matsui S, Saeki T, Tsuboi H, Dobashi H, Susaki K, Morimoto H, Takagi K, Kawano M, Origuchi T, Wada Y, Takahashi N, Horikoshi M, Ogishima, H, Suzuki Y, Kawanami T, Kawanami (Iwao) H, Sakai T, Suzuki R, Morikawa Y, Yoshino T, Nakamura S, Kojima M, Kurose N, Sugai S, Sumida T.
  • Journal Title: Mod Rheumatol Volume: 15 Issue: 5 Pages: 1-6
  • DOI: 10.1080/14397595.2016.1259602
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Proposed diagnostic criteria, disease severity classification and treatment strategy for TAFRO syndrome, 2015 version. (2016)
  • Author(s): Masaki Y, Kawabata H, Takai K, Kojima M, Tsukamoto N, Ishigaki Y, Kurose N, Ide M, Murakami J, Nara K, Yamamoto H, Ozawa Y, Takahashi H, Miura K, Miyauchi T, Yoshida S, Momoi A, Awano N, Ikushima S, Ohta Y, Furuta N, Fujimoto S, Kawanami H, Sakai T, Kawanami T, Fujita Y, Fukushima T, Nakamura S, Kinoshita T, Aoki S.
  • Journal Title: Int J Hematol. Volume: in press Issue: 6 Pages: 686-92
  • DOI: 10.1007/s12185-016-1979-1
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Isolation of vascular smooth muscle antigen-reactive CD4(+)αβTh1 clones that induce pulmonary vasculitis in MRL/Mp-Fas(+/+) mice. (2016)
  • Author(s): Fujita Y, Fujii T, Shimizu H, Sato T, Nakamura T, Iwao H, Nakajima A, Miki M, Sakai T, Kawanami T, Tanaka M, Masaki Y, Fukushima T, Okazaki T, Umehara H, Mimori T.
  • Journal Title: Cell Immunol. Volume: 303 Pages: 50-54
  • DOI: 10.1016/j.cellimm.2016.03.004
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Prospective clinical study of R-CMD therapy for indolent B cell lymphoma and mantle cell lymphoma from the Hokuriku Hematology Oncology Study Group (2015)
  • Author(s): Sakai T, Masaki Y, Otsuki N, Sakamaki I, Kishi S, Miyazono T, Urasaki Y, Murakami J, Satoh T, Nakamura T, Iwao H, Nakajima A, Kawanami T, Miki M, Fujita Y, Tanaka M, Fukushima T, Okazaki T, Ueda T.
  • Journal Title: Medical Oncology Volume: 32 Issue: 9 Pages: 232-238
  • DOI: 10.1007/s12032-015-0677-9
  • Peer Reviewed / Open Access
• [Journal Article] <b>CD14</b>^<b>+</b><b> follicular dendritic cells in lymphoid follicles may play a role in the pathogenesis of IgG4-related </b><b>disease </b> (2015)
  • Author(s): Tomomi Satoh-Nakamura, Nozomu Kurose, Takafumi Kawanami, Takuji Nakamura, Haruka Iwao-Kawanami, Akio Nakajima, Miyuki Miki, Tomoyuki Sakai, Yoshimasa Fujita, Masao Tanaka, Toshihiro Fukushima, and Yasufumi Masaki
  • Journal Title: Biomedical Research Volume: 36 Issue: 2 Pages: 143-153
  • DOI: 10.2220/biomedres.36.143
  • NAID: 130005065277
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Decreased Expression of Innate Immunity-Related Genes in Peripheral Blood Mononuclear Cells from Patients with IgG4-Related Disease (2015)
  • Author(s): Nakajima A, Masaki Y, Nakamura T,et al.
  • Journal Title: Pros One Volume: １０ Issue: 5 Pages: e0126582-e0126582
  • DOI: 10.1371/journal.pone.0126582
  • Peer Reviewed / Open Access
• [Presentation] IgG4関連疾患における疾患特異的に変動する代謝物群を利用した メタボロミクス解析 (2019)
  • Author(s): 河南崇典、藤本信乃、 藤田義正、川端 浩、正木康史
  • Organizer: 第62回 日本リウマチ学会
• [Presentation] IgG4関連疾患の炎症の発生と収束にかかわる脂質メディエーターとそのバランス制御 (2016)
  • Author(s): 河南 崇典
  • Organizer: 第9回 IgG4研究会
  • Place of Presentation: ピュアリティまきび（岡山県、岡山市）
  • Year and Date: 2016-03-19
• [Presentation] プロテオミクスの手法を用いたIgG4関連疾患特異的に変動するタンパク質の機能解析 (2016)
  • Author(s): 河南 崇典、岩男 悠、藤本 信乃、坂井 知之、藤田 義正、福島 俊洋、岡崎 俊朗、正木 康史
  • Organizer: 第25回 日本シェーグレン症候群学会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）