Basic analysis of clinical significance of novel vasculitis biomarkers identified by a peptidomic approach

• Project/Area Number: 25461489
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Ozaki Shoichi 聖マリアンナ医科大学, 医学部, 教授 (00231233)
• Co-Investigator(Kenkyū-buntansha): KUROKAWA Manae 聖マリアンナ医科大学, 医学部, 准教授 (90301598)
• Co-Investigator(Renkei-kenkyūsha): NAGAFUCHI Hiroko 聖マリアンナ医科大学, 医学部, 講師 (80278001)
• Research Collaborator: OHMOTO Yasukazu
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ANCA関連血管炎 / ペプチドミクス / アポリポタンパク / 血管炎 / バイオマーカー / MPO-ANCA

Outline of Final Research Achievements

We established two quantitative assay systems of serum AC13 levels. One method is a competitive ELISA system with serum samples which have been applied to a centrifugal ultra- filter 10K devices in order to eliminate serum ApoA-I that cross-react with AC13. The other method is a quantitative mass spectrometry using stable isotope-labeled AC13 as an internal control. A representative standard curve showed R2=0.9802, suggesting the usefulness of this quantitative method.
To investigate the function of AC13, we analyzed the protein profiles of human micro vascular endothelial cells (hMVEC) cultured in the presence or absence of AC13. AC13 appeared to augment the TNF-mediated inflammation and ERK1/2-induced cell proliferation and adhesion, resulting in the exacerbation of vasculitis. We also demonstrated that biotinated AC13 bound to hMVEC, suggesting the presence of AC13-bindng protein or receptor on the cell surface.

Research Products

• [Journal Article] Aberrant glycosylation of lumican in aortic valve stenosis revealed by a proteomic analysis. (2016)
  • Author(s): Suzuki H, Chikada M, Yokoyama MK, Kurokawa MS, Ando T, Furukawa H, Arito M, Miyairi T, Kato T.
  • Journal Title: Int Heart J Volume: 19(57) Pages: 104-111
  • Peer Reviewed
• [Journal Article] Left heart abonormalities in connective tissue diseases patients with precapillary pulmonary hypertension as well as borderline mean pulmonary arterial pressure. (2015)
  • Author(s): Tsuchida K, Yamada H, Yamasaki Y, Suzuki K, Kongoji K, Akashi Y, Ozaki S.
  • Journal Title: Mod Rheumatol Volume: 25(5) Issue: 5 Pages: 744-747
  • DOI: 10.3109/14397595.2015.1005871
  • Peer Reviewed
• [Journal Article] Clinical subsets associated with different anti-aminoacyl transter RNA synthetase antibodies and their association with coexisting anti-Ro52. (2015)
  • Author(s): Yamasaki Y, Satoh M, Mizushima M, Okazaki T, Nagafuchi H, Ooka S, Shibata T, Nakano H, Ogawa H, Azuma K, Maeda A, Tonooka K, Ito H, Takakuwa Y, Inoue M, Kiyokawa T, Tsuchida K, Matsushita H, Mikage H, Murakami Y, Jason Y. F. Chan, Ozaki S, Yamada H.
  • Journal Title: Mod Rheumatol Volume: 1 Issue: 3 Pages: 403-9
  • DOI: 10.3109/14397595.2015.1091155
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Serum peptides as candidate biomarkers for dementia with Lewy bodies. (2015)
  • Author(s): Suzuki I, Noguchi M, Arito M, Sato T, Omoteyama K, Maedomari M, Hasegawa H, Suematsu N, Okamoto K, Kato T, Yamaguchi N, Kurokawa MS.
  • Journal Title: Int J Geriatr Psychiatry Volume: 30 Pages: 1195-1206
  • NAID: 130007499679
  • Peer Reviewed
• [Journal Article] Altered acetylation of proteins in patients with rheumatoid arthritis, revealed by acetyl-proteomics. (2015)
  • Author(s): Arito M, Nagai K, Ooka S, Sato T, Takakuwa Y, Kurokawa MS, Sase T, Okamoto K, Suematsu N, Kato T.
  • Journal Title: Clin Exp Rheumatol Volume: 33 Pages: 877-886
  • Peer Reviewed
• [Journal Article] Effects of methotrexate and salazosulfapyridine on protein profiles of exosomes derived from a human synovial sarcoma cell line of SW982. (2015)
  • Author(s): Tsuno H, Suematsu N, Sato T, Arito M, Matsui T, Iizuka N, Omoteyama K, Okamoto K, Tohma S, Kurokawa MS, Kato T.
  • Journal Title: Proteomics - Clin Applications Volume: 1
  • Peer Reviewed
• [Journal Article] Association of IRF5 polymorphism with MPO-ANCA-positive vasculitis in a Japanese population. (2014)
  • Author(s): Kawasaki A., Inoue N., Ajimi C., Sada K-e., Kobayashi S., Yamada H., Furukawa H., Sumida T., Tohma S., Miyasaka N., Matsuo S., Ozaki S., Hashimoto H., Makino H., Harigai M., Tsuchiya N.
  • Journal Title: Genes and Immunity Volume: 1(1) Pages: 1-2
  • Peer Reviewed
• [Journal Article] Long-term safety and efficacy of rituximab in 7 Japanese patients with ANCA-associated vasculitis. (2014)
  • Author(s): Nagafuchi H., Atsumi T., Hatta K., Muso E., Takeno M., Yamada H., Ozaki S.:
  • Journal Title: Mod Rheumatol Volume: 15 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Proteomic analysis of whole glomeruli in patients with IgA nephropathy using micro- sieving. (2014)
  • Author(s): Kojima S, Koitabashi K, Iizuka N, Okamoto K, Arito M, Sato T, Kurokawa MS, Suematsu N, Shibagaki Y, Yasuda T, Kimura K, Kato T.
  • Journal Title: Am J Nephrol Volume: 29 Pages: 36-45
  • Peer Reviewed
• [Journal Article] Assessment of the Birmingham vasculitis activity score in patients with MPO-ANCA-associated vasculitis: sub-analysis from a study by the Japanese Study Group for MPO-ANCA-associated vasculitis. (2014)
  • Author(s): Yumura W, Kobayashi S, Suka M, Hayashi T, Ito S, Nagafuchi H, Yamada H, Ozaki S.
  • Journal Title: Mod Rheumatol. Volume: 24(2) Pages: 304-309
  • Peer Reviewed
• [Journal Article] Comparison of phenotype and outcome in microscopic polyangiitis between Europe and Japan. (2014)
  • Author(s): Furuta, S., Chaudhry, AN., Hamano, Y., Fujimoto, S., Nagafuchi, H., Makino, H., Matsuo, S., Ozaki, S., Endo, T., Muso, E., Ito, C., Kusano, E., Yamagata, M., Ikeda, K., Kashiwakuma, D., Iwamoto, I., Westman, K. and Jayne, D.
  • Journal Title: J Rheumatol. Volume: 41(2) Issue: 2 Pages: 325-33
  • DOI: 10.3899/jrheum.130602
  • Peer Reviewed / Open Access
• [Journal Article] Serum level of soluble triggering receptor expressed on myeloid cells-1 as a biomarker of disease activity in relapsing polychondritis. (2014)
  • Author(s): Sato T, Yamano Y, Tomaru U, Shimizu Y, Ando H, Okazaki T, Nagafuchi H, Shimizu J, Ozaki S, Miyazawa T, Yudoh K, Oka H, Suzuki N.
  • Journal Title: Mod Rheumatol. 2014 Jan;: Volume: 24(1) Pages: 129-136
  • Peer Reviewed
• [Journal Article] Clinical trial for Japanese patients with myeloperoxidase anti-neutrophil cytoplasmic antibody-associated vasculitis: the JMAAV study. (2013)
  • Author(s): Ozaki S.
  • Journal Title: Clin Exp Nephrol. Volume: 17(5) Issue: 5 Pages: 700-704
  • DOI: 10.1007/s10157-013-0821-9
  • Peer Reviewed
• [Journal Article] Prediction of response to treatment by gene expression profiling of peripheral blood in patients with microscopic polyangiitis. (2013)
  • Author(s): Ishizu A, Tomaru U, Murai T, Yamamoto T, Atsumi T, Yoshiki T, Yumura W, Yamagata K, Yamada H, Kumagai S, Kurokawa MS, Suka M, Makino H, Ozaki S.
  • Journal Title: PLOS ONE Volume: 8 Issue: 5 Pages: e63182-e63182
  • DOI: 10.1371/journal.pone.0063182
  • Peer Reviewed
• [Journal Article] Comparative proteomic analysis of neutrophils from patients with microscopic polyangiitis and granulomatosis with polyangiitis (2013)
  • Author(s): Kurokawa MS, et al
  • Journal Title: J Proteomics Volume: 91C Pages: 259-69
  • DOI: 10.1016/j.jprot.2013.07.021
  • NAID: 130005454504
  • Peer Reviewed
• [Presentation] プロテオミクスを用いたRAの病態解析 (2015)
  • Author(s): 黒川真奈絵、有戸光美、加藤智啓
  • Organizer: 第43回日本関節病学会
  • Place of Presentation: 札幌コンベンションセンター(北海道・札幌市)
  • Year and Date: 2015-11-05
• [Presentation] シェドミクス法の確立に関する研究 (2015)
  • Author(s): 表山和樹、有戸光美、佐藤利行、岡本一起、末松直也、黒川真奈絵、加藤智啓
  • Organizer: 日本プロテオーム学会2015年会
  • Place of Presentation: 熊本森都心プラザ(熊本県・熊本市)
  • Year and Date: 2015-07-23
• [Presentation] Serum peptides as candidate biomarkers for dementia with Lewy bodies. (2015)
  • Author(s): Kurokawa MS, Arito M, Sato T, Omoteyama K, Suematsu N, Okamoto K, Kato T.
  • Organizer: 日本プロテオーム学会2015年会
  • Place of Presentation: 熊本森都心プラザ(熊本県・熊本市)
  • Year and Date: 2015-07-23
• [Presentation] Serum peptides as candidate biomarkers for dementia with Lewy bodies. (2015)
  • Author(s): Kurokawa MS, Suzuki I, Noguchi M, Arito M, Sato T, Omoteyama K, Maedomari M, Hasegawa H, Suematsu N, Okamoto K, Kato T, Yamaguchi N.
  • Organizer: 第11回日本臨床プロテオーム研究会
  • Place of Presentation: 国立がん研究センター(東京都・中央区)
  • Year and Date: 2015-05-23
• [Presentation] Aberrant Glycosylation of Lumican in Aortic Valve Stenosis Revealed by a Proteomic Analysis. (2015)
  • Author(s): Suzuki H, Chikada M, Yokoyama M, Kurokawa MS, Furukawa H, Arito M, Miyairi T, Kato T.
  • Organizer: 23th ASCVTS 2015
  • Place of Presentation: 香港
  • Year and Date: 2015-05-11
• [Presentation] 日本人集団におけるANCA関連血管炎の遺伝要素 (2015)
  • Author(s): 土屋尚之、長谷部成美、日高操希、佐藤憲映、小林茂人、山田秀裕、古川宏、山縣邦弘、住田孝之、宮坂信之、富間重人、尾崎承一、松尾清一、橋本博史、槇野博史、有村義宏、針谷正祥、川崎綾
  • Organizer: 第59回日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋国際会議場(愛知県・名古屋市)
  • Year and Date: 2015-04-23
• [Presentation] リツキシマブによる寛解導入療法が行われたANCA関連血管炎13例の有用性の検討 (2015)
  • Author(s): 大慈彌久絵、松下広美、内田貞輔、三冨博文、伊東宏、山崎宜興、大岡正道、岡崎貴裕、山田秀裕、尾崎承一
  • Organizer: 第59回日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋国際会議場(愛知県・名古屋市)
  • Year and Date: 2015-04-23
• [Presentation] ANCA関連血管炎における好中球ミエロペルオキシターゼの酸化修飾 (2015)
  • Author(s): 内田貞輔、永井宏平、佐藤利行、大岡正道、有戸光美、尾崎承一、黒川真奈絵、加藤智啓
  • Organizer: 第59回日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋国際会議場(愛知県・名古屋市)
  • Year and Date: 2015-04-23
• [Presentation] サーフェスオミックスを利用したサラゾスルファピリジンの作用の解析 (2015)
  • Author(s): 表山和樹、佐藤利行、有戸光美、末松直也、黒川真奈絵、加藤智啓
  • Organizer: 第59回日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋国際会議場(愛知県・名古屋市)
  • Year and Date: 2015-04-23
• [Presentation] ヒト関節軟骨細胞におけるLayilinを介したシグナルによる炎症因子の誘導 (2015)
  • Author(s): 有戸光美、黒川真奈絵、表山和樹、遊道和雄、中村洋、別府諸兄、加藤智啓
  • Organizer: 第59回日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋国際会議場(愛知県・名古屋市)
  • Year and Date: 2015-04-23
• [Presentation] Novel roles ofr ｚｙｘｉｎ ｉｎ the pathogenesis of giant cell arteritis. (2014)
  • Author(s): Karasawa R., Paul A Monach, Tamai M., Okazaki T., Ohishi M., Kodera Y., Sato T., Ozaki S., Kaiyu Jiang, Yudo K., James N. Javis, Peter A. Merkel. :
  • Organizer: American College of Rheumatology 2014
  • Place of Presentation: Boston, U.S.A
  • Year and Date: 2014-11-13 – 2014-11-17
• [Presentation] Oxidative modification in myeloperoxidase in patients with antineutrophil cytoplasmic antibody(ANCA)-axxociated vasculitides. (2014)
  • Author(s): Uchida Teisuke, Nagai Kouhei, Sato Toshiyuki, Iizuka Nobuko, Arito Mitusmi, Takakuwa Yukiko, Nakano Hiromasa, Ooka Seido, Kurokawa Manae, Okamoto Kazuki, Ozaki Shoichi, Kato Tomohiro
  • Organizer: 第58回日本リウマチ学会総会・学術集会
  • Place of Presentation: グランドプリンスホテル新高輪(東京都港区)
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] Protein profiles of peripheral blood monomuclear cells as a candidate biomarker for Behcet’s disease. (2014)
  • Author(s): Yoshioka Takuya, Kurokawa Manae, Sato Toshiyuki, Nagai Kouhei, Iizuka Nobuko, Arito Mitsumi, Takakuwa Yukiko, Nakano Hiromasa, Ooka Seido, Okamoto Kazuki, Yudoh Kazuo, Nakamura Hiroshi, Suzuki Noboru, Ozaki Shoichi, Kato Tomohiro
  • Organizer: 第58回日本リウマチ学会総会・学術集会
  • Place of Presentation: グランドプリンスホテル新高輪(東京都港区)
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 血管炎の新しい治療―Biologicsなど (2013)
  • Author(s): 尾崎承一
  • Organizer: 第57回日本リウマチ学会総会・学術集会
  • Place of Presentation: 国立京都国際会館
• [Presentation] ベーチェット病患者の末梢血単核球に発現している蛋白質の網羅的解析 (2013)
  • Author(s): 黒川真奈絵、吉岡拓也、佐藤利行、永井宏平、飯塚進子、有戸光美、高桑由希子、中野弘雅、大岡正道、岡本一起、中村洋、鈴木登、尾崎承一、加藤智啓
  • Organizer: 第57回日本リウマチ学会総会・学術集会
  • Place of Presentation: 国立京都国際会館
• [Presentation] ANCA関連血管炎とUBE2L3、TNIP1遺伝子多型の関連研究 (2013)
  • Author(s): 長谷部成美、川崎綾、小林茂人、佐田憲映、山田秀裕、古川宏、當間重人、住田孝之、宮坂信之、尾崎承一、橋本博史、槇野博史、針谷正祥、土田尚之
  • Organizer: 第57回日本リウマチ学会総会・学術集会
  • Place of Presentation: 国立京都国際会館
• [Presentation] ANCA関連血管炎におけるSTAT4、IRF5遺伝子多型の関連研究 (2013)
  • Author(s): 井上尚哉、川崎綾、小林茂人、佐田憲映、山田秀裕、古川宏、當間重人、住田孝之、宮坂信之、尾崎承一、橋本博史、槇野博史、針谷正祥、土田尚之
  • Organizer: 第57回日本リウマチ学会総会・学術集会
  • Place of Presentation: 国立京都国際会館
• [Presentation] Comparative proteomic analysis of neutrophils from patients with microscopic polyangiitis and granulomatosis with polyangiitis. (2013)
  • Author(s): Uchida T., Nagai K., Sato T., Takakuwa Y., Nakano H., Ooka S., Arito M., Iizuka N., Okamoto K., Kurokawa M., Ozaki S., Kato T.
  • Organizer: 第57回日本リウマチ学会総会・学術集会
  • Place of Presentation: 国立京都国際会館
• [Presentation] Protein profiles of peripheral blood mononuclear cells a a biomarker for Behcet’s disease. (2013)
  • Author(s): Yoshioka T., Kurokawa M., Sato T., Nagai K., Iizuka N., Arito M., Takakuwa Y., Nakano H., Ooka S., Suematsu N., Okamoto K., Nakamura H., Suzuki N., Ozaki S., Kato T.
  • Organizer: American College of Rheumatology 2013.
  • Place of Presentation: San Diego, U.S.A.
• [Presentation] Comparative proteomic analysis of neutrophils from patients with microscopic polyangitis and granulomatosis with polyangiitis. (2013)
  • Author(s): Uchida T., Nagai K., Sato T., Iizuka N., Arito M., Takakuwa Y., Nakano H., Ooka S., Kurokawa M., Suematsu M., Okamoto K., Ozaki S., Kato T.
  • Organizer: American College of Rheumatology 2013.
  • Place of Presentation: San Diego, U.S.A.
• [Presentation] Comparative croteomic analysis of neutrophils from patients with microscopic polyangiitis and granulomatosis with polyangiitis. (2013)
  • Author(s): Uchida T, Nagai K, Sato T, IizukaN, Arito M, Takakuwa Y, Nakano H, Ooka S, Kurokawa MS, Suematsu N, Okamoto K, Ozaki S, Kato T.
  • Organizer: HUPO2013
  • Place of Presentation: 横浜市
• [Presentation] Protein profiles of peripheral blood mononuclear cells as a biomarker for Behcet’s Disease. (2013)
  • Author(s): Yoshioka T, Kurokawa MS, Sato T, Nagai K, Iizuka N, Arito M, Takakuwa Y, Nakano H, Ooka H, Suematsu N, Okamoto K, Nakamura H, Suzuki N, Ozaki S, Kato T.
  • Organizer: HUPO2013
  • Place of Presentation: 横浜市