Metabolomic analysis in IgG4-related disease

• Project/Area Number: 24591459
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kanazawa Medical University
• Principal Investigator: IWAO Haruka 金沢医科大学, 医学部, 助教 (10612244)
• Co-Investigator(Kenkyū-buntansha): UMEHARA Hisanori 金沢医科大学, 医学部, 教授 (70247881) ; KAWANAMI Takafumi 金沢医科大学, 医学部, 講師 (20350762) ; MASAKI Yasufumi 金沢医科大学, 医学部, 教授 (40238895) ; TANAKA Masao 京都大学, 医学部, 特定准教授 (10332719)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: IgG4関連疾患 / メタボロミクス / 脂質メディエーター / IgG4関連疾患診断基準

Outline of Final Research Achievements

IgG4-related disease is indicated by increased infiltration of IgG4-positive plasma cells, typically elevated IgG4 serum levels and the formation of lymphoplasmacytic infiltrate in one or more organs. We explored the metabolome of >400 small molecules in serum from 10 matched pair IgG4-related disease subjects prior to (PRE) and following (POST) steroid treatment and contrast these profiles with a cohort of 10 normal non-diseased subjects (NORM). The polyunsaturated fatty acid arachidonate is involved in pro-inflammatory activities through its metabolism to the pro-inflammatory prostaglandins via cyclooxygenase activity and HETEs via lipoxygenases. Individuals with PRE IgG4-related disease had elevated arachidonate and the 12-lipoxygenase product, 12-HETE, as compared to NORM subjects. The higher levels of the pro-inflammatory arachidonate and 12-HETE was unaffected by steroid treatment as POST subjects had similar levels of these biochemicals as was observed in PRE subjects.

Research Products

• [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
• [Journal Article] Decreased expression of innate immunity-related genes in peripheral blood mononuclear cells from patients with IgG4-related disease (2015)
  • Author(s): Akio Nakajima, Yasufumi Masaki, Takuji Nakamura, Takafumi Kawanami, Yasuhito Ishigaki, Tsutomu Takegami, Mitsuhiro Kawano, Kazunori Yamada, Norifumi Tsukamoto, Shoko Matsui, Takako Saeki, Kazuichi Okazaki, Terumi Kamisawa, Taiichiro Miyashita, Yoshihiro Yakushijin, Keita Fujikawa, Motohisa Yamamoto, Haruka Iwao, et al.
  • Journal Title: PLOS ONE Volume: -
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] IgG4-related disease:Diagnostic methods and therapeutic strategies in Japan (2014)
  • Author(s): Y.Masaki, H.Shimizu, T.Sato, T.Nakamura, A.Nakajima, H.Iwao, M.Miki, T.Sakai, T.Kawanami, Y.Fujita, M.Tanaka, and T. Fukushima
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 54 Pages: 95-101
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] IgG4関連疾患の診断 (2014)
  • Author(s): 梅原久範, 三木美由貴, 岩男 悠, 中島章夫
  • Journal Title: 神経内科 Volume: 80 Pages: 157-162
  • Peer Reviewed
• [Journal Article] Japanese variant of multicentric castleman's disease associated with serositis and thrombocytopenia--a report of two cases: is TAFRO syndrome (Castleman- Kojima disease) a distinct clinicopathological entity? (2013)
  • Author(s): Y.Masaki, A.Nakajima, H.Iwao, N.Kurose, T.Sato, T.Nakamura, M.Miki, T.Sakai, T.Kawanami, T.Sawaki, Y.Fujita, M.Tanaka, T.Fukushima, T.Okazaki, H.Umehara
  • Journal Title: J. Clin. Exp. Hematop. Volume: 53 Pages: 79-85
  • NAID: 10031183131
  • Peer Reviewed
• [Journal Article] Cutoff Values of Serum IgG4 and Histopathological IgG4+ Plasma Cells for Diagnosis of Patients with IgG4-Related Disease. (2013)
  • Author(s): Masaki Y, Kurose N, Yamamoto M, ,Yamada K, Kawano M, ,Eguchi K, Sugai S, Umehara H.
  • Journal Title: Int J Rheumatol. Volume: Epub ahead of print Pages: 580814-580814
  • DOI: 10.1155/2012/580814
  • Peer Reviewed
• [Journal Article] CD4+ T-cell dysfunctions through the impaired lipid rafts ameliorate concanavalin A-induced hepatitis in sphingomyelin synthase 1-knockout mice (2012)
  • Author(s): Dong L, Watanabe K, Itoh M, Huan CR, Tong XP, Nakamura T, Miki M, Iwao H, Nakajima A, Sakai T, Kawanami T, Sawaki T, Masaki Y, Fukushima T, Fujita Y, Tanaka M, Yano M, Okazaki T and Umehara H
  • Journal Title: International immunology Volume: 24 Issue: 5 Pages: 327-337
  • DOI: 10.1093/intimm/dxs008
  • Peer Reviewed
• [Journal Article] Skewed production of IL-6 and TGFbeta by cultured salivary gland epithelial cells from patients with Sjogren's syndrome (2012)
  • Author(s): Kawanami T, Sawaki T, Sakai T, Miki M, Iwao H, Nakajima A, Nakamura T, Sato T, Fujita Y, Tanaka M, Masaki Y, Fukushima T, Hirose Y, Taniguchi M, Sugimoto N, Okazaki T and Umehara H
  • Journal Title: PLoS One Volume: 7 Issue: 10 Pages: e45689-e45689
  • DOI: 10.1371/journal.pone.0045689
  • Peer Reviewed
• [Journal Article] Daily 500mg valacyclovir is effective for prevention of varicella zoster virus reactivation in patients with multiple myeloma treated with bortezomib (2012)
  • Author(s): T.Fukushima
  • Journal Title: Anticancer Res. Volume: 32 Pages: 5437-5440
  • Peer Reviewed
• [Journal Article] Low-dose cytarabine plus aclarubicin for patients with previously untreated acute myeloid leukemia or high-risk myelodysplastic syndrome ineligible for standard-dose cytarabine plus anthracline (2012)
  • Author(s): T.Fukushima
  • Journal Title: Anticancer Res Volume: 32(4) Pages: 1347-53
  • Peer Reviewed
• [Presentation] 「IgG4＋MOLPS(IgG4関連多臓器リンパ増殖症候群)、Castleman病その他の多クローン性高γグロブリン血症の鑑別診断のための他施設共同前方視的臨床研究」の中間報告 (2013)
  • Author(s): 岩男 悠, 正木康史, 佐伯敬子, 松井祥子, 川野充弘, 平田信太郎, 藤川敬太, 折口智樹, 宮下賜一郎, 坪井洋人, 梅原久範
  • Organizer: 第57回日本リウマチ学会総会・学術集会／第22回国際リウマチシンポジウム
  • Place of Presentation: 国立京都国際会館, 京都府京都市
• [Presentation] 厚労省(旧)梅原班におけるIgG4関連疾患前方視的他施設共同研究の中 間解析結果 (2013)
  • Author(s): 岩男 悠
  • Organizer: 日本リンパ網内系学会
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] 「IgG4+MOLPS（IgG4関連多臓器リンパ増殖症候群）、Castleman病 その他の多クローン性高γグロブリン血症の鑑別診断のための多施設共同前方視的臨床研究」中間報告 (2013)
  • Author(s): 岩男 悠
  • Organizer: 日本リウマチ学会
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] トロンボポエチン受容体作動薬が有効であったSLE合併難治性血小板減少症の一例 (2012)
  • Author(s): 岩男 悠
  • Organizer: 日本リウマチ学会
  • Place of Presentation: グランドプリンスホテル新高輪（東京）
• [Remarks] IgG4+MOLPS：Mikulicz病検討会
  • URL: http://www.kanazawa-med.ac.jp/&#771;hematol/topics4.html
• [Remarks] IgG4+MOLPS：Mikulicz病検討会
  • URL: http://www.kanazawa-med.ac.jp/~hematol/topics4.html