難治性内因性ぶどう膜炎における網羅的自己抗体解析研究

2012 Fiscal Year Research-status Report

• Project/Area Number: 23592602
• Research Institution: Hokkaido University
• Principal Investigator: 大野 重昭 北海道大学, 医学(系)研究科(研究院), 特任教授 (50002382)
• Co-Investigator(Kenkyū-buntansha): 石田 晋 北海道大学, 医学(系)研究科(研究院), 教授 (10245558) ; 南塲 研一 北海道大学, 大学病院, 講師 (70333599) ; 北市 伸義 北海道大学, 医学(系)研究科(研究院), 客員准教授 (40431366) ; 目黒 明 横浜市立大学, 医学(系)研究科(研究院), 特任助教 (60508802)
• Keywords: 内因性ぶどう膜炎 / 自己抗体

Research Abstract

研究実施計画に則り研究を遂行し、本実験系における自己抗体検出システムの測定精度、実験者の手技、およびプロトコールはほぼ安定的に確立することが出来たと判断している。ベーチェット病患者2症例から、新たな自己抗体の標的タンパク13種類が検出された。コントロールに比べ3倍～20倍の値を示した。他のぶどう膜炎疾患においてこれら自己抗体の産生は認められなかったため、これらがベーチェット病において特異的に産生されるものである可能性がある。検体は眼病変主体のものと消化管病変主体のものであるが、上記13種タンパク質に対して同様に抗体が産生されていることが分かった。今後さらに検討していく予定である。
24年度には予想外の新たな発見もあった。癌関連網膜症の一種であるBilateral diffuse uveal melanocytic proliferation (BDUMP)の一症例についても検討したところ、2種類のタンパクに対しコントロールと比較し数百倍といった自己抗体の存在が明らかとなった。しかもこれは卵巣の明細胞癌に起因する網膜症症例であった。現在他の明細胞癌患者検体を収集しており、発見した自己抗体が明細胞癌はなくBDUMPに特異的に出現してくる抗体であることを今後調べていく予定である。
25年度はこれら13種類と２種類のタンパク質の解析をさらに進め、自己抗体プロフィールの網羅的な解析を完了させることで、ぶどう膜炎特異的自己抗体を指標とした病態解析および診断技術の開発が可能になることが期待される。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

ほぼ研究実施計画通りに進行し、内因性ぶどう膜炎の標的タンパク候補が13種類検出できた。一方、癌関連網膜症症例から、当初予想していなかった、健常者の数百倍の値を示すタンパクを２種類新たに見いだした。本年度はこの２種類も合わせて詳細に検討する予定である。

Strategy for Future Research Activity

今年度はこれらタンパク質の解析をさらに進め、今後自己抗体プロフィールの網羅的な解析を完了させることで、ぶどう膜炎特異的自己抗体を指標とした病態解析および診断技術の開発が可能になることが期待される。

Expenditure Plans for the Next FY Research Funding

25年度は検索対象症例、疾患対照者、および健常対照者がさらに増加する予定であり、研究費は計画通り使用される予定である。

Research Products

• [Journal Article] Reduction of intraocular pressure using a modified 360-degree suture trabeculotomy technique in primary and secondary open-angle glaucoma: A pilot study (2012)
  • Author(s): Chin S, Nitta T, Shinmei Y, Aoyagi M, Nitta A, Ohno S, Ishida S, Yoshida K.
  • Journal Title: J Glaucoma Volume: 21 Pages: 401-407
  • DOI: 10.1097/IJG.0b013e318218240c.
  • Peer Reviewed
• [Journal Article] Replication of a microsatellite genome-wide association study of Behcet disease in a Korean population. (2012)
  • Author(s): Horie Y, Meguro A, Kitaichi N, Lee E B, Kanda A, Noda K, Song Y W, Park K S, Namba K, Ota M, Inoko H, Mizuki N, Ishida S, Ohno S.
  • Journal Title: Rheumatology Volume: 51 Pages: 983-986
  • DOI: 10.1093/rheumatology/ker444
  • Peer Reviewed
• [Journal Article] Intravitreal injection of bevacizumab in a case of occlusive retinal vasculitis accompanied with syphilitic intraocular inflammation. (2012)
  • Author(s): Ishijima K, Namba K, Ohno S, Mochizuki K, Ishida S.
  • Journal Title: Case Report Ophthalmol. Volume: 3 Pages: 434-437
  • DOI: 10.1159/000346046
  • Peer Reviewed
• [Journal Article] Correlation between elevation of serum antinuclear antibody titre and decreased therapeutic efficacy in the treatment of Behçet’s disease with infliximab. (2012)
  • Author(s): Iwata D, Namba K, Mizuuchi K, Kitaichi N, Kase S, Takemoto Y, Ohno S, Ishida S.
  • Journal Title: Graefes Arch Clin Exp Ophthalmol Volume: 250 Pages: 1081-1087
  • DOI: 10.1007/s00417-011-1908-1.
  • Peer Reviewed
• [Journal Article] Chickenpox chorioretinitis with retinal exudates and periphlebitis. (2012)
  • Author(s): Kitamei H, Namba K, Kitaichi N, Wakayama A, Ohno S, Ishida S.
  • Journal Title: Case Report Ophthalmol. Volume: 3 Pages: 180-184
  • DOI: 10.1159/000339128.
  • Peer Reviewed
• [Journal Article] Amelioration of ultraviolet-induced photokeratitis in mice treated with astaxanthin eye drops. (2012)
  • Author(s): Lennikov A, Kitaichi N, Fukase R, Murata M, Noda K, Ando R, Ohguchi T, Kawakita T, Ohno S, Ishida S.
  • Journal Title: Mol Vis. Volume: 18 Pages: 455-464
  • Peer Reviewed
• [Journal Article] Amelioration of endotoxin-induced uveitis treated with an IκB kinase β inhibitor in rats. (2012)
  • Author(s): Lennikov A, Kitaichi N, Noda K, Ando R, Dong Z, Fukuhara J, Kinoshita S, Namba K, Mizutani M, Fujikawa T, Itai A, Ohno S, Ishida S.
  • Journal Title: Mol Vis. Volume: 18 Pages: 2586-2597
  • Peer Reviewed
• [Journal Article] Multicenter study of infliximab for refractory uveoretinitis in Behcet disease. (2012)
  • Author(s): Okada AA, Goto H, Ohno S, Mochizuki M, Kitaichi N, Namba K, Keino H, Watanabe T, Ishibashi T, Ito T, Sonoda K, Nakai K, Ohguro N, Sugita S, Kezuka T, Kaburaki T, Takamoto M, Mizuki N.
  • Journal Title: Arch Ophthalmol. Volume: 130 Pages: 592-598
  • DOI: 10.1001/archophthalmol.
  • Peer Reviewed
• [Journal Article] Astaxanthin increases choroidal blood flow velocity. (2012)
  • Author(s): Saito M, Yoshida K, Saito W, Fujiya A, Ohgami K, Kitaichi N, Tsukahara H, Ishida S, Ohno S
  • Journal Title: Graefes Arch Clin Exp Ophthalmol. Volume: 250 Pages: 239-245
  • DOI: 10.1007/s00417-011-1843-1.
  • Peer Reviewed
• [Journal Article] Lack of association between IL10 polymorphisms and sarcoidosis in Japanese patients. (2012)
  • Author(s): Sakuyama K, Meguro A, Ota M, Ishihara M, Uemoto R, Ito H, Okada E, Namba K, Kitaichi N, Morimoto S, Kaburaki T, Ando Y, Takenaka S, Yuasa T, Ohno S, Inoko H, Mizuki N.
  • Journal Title: Mol Vis. Volume: 18 Pages: 512-518
  • Peer Reviewed
• [Journal Article] Genetic characterization and susceptibility for sarcoidosis in Japanese patients: Risk factors of BTNL2 gene polymorphisms and HLA class II alleles. (2012)
  • Author(s): Suzuki H, Ota M, Meguro A, Katsuyama Y, Kawagoe T, Ishihara M, Ohno S（22番目）et al 計24名
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 53 Pages: 7109-7115
  • DOI: 10.1167/iovs.12-10491.
  • Peer Reviewed
• [Presentation] Management dilemmas in uveitis. (2012)
  • Author(s): Ohno S, Chin S.
  • Organizer: Second Biennial National Conference,
  • Place of Presentation: Bangladesh Uvea Society：Dhaka, Bangladesh
  • Year and Date: 20121215-20121215
  • Invited
• [Presentation] Presentation perspectives in Vogt-Koyanagi-Harada disease. (2012)
  • Author(s): Ohno S.
  • Organizer: Second Biennial National Conference,
  • Place of Presentation: Bangladesh Uvea Society：Dhaka, Bangladesh
  • Year and Date: 20121215-20121215
  • Invited
• [Presentation] Corticosteroid therapy in uveitis. (2012)
  • Author(s): Ohno S.
  • Organizer: Ophthalmology Seminar
  • Place of Presentation: Thimpu National Referral Hospital: Thimpu, Bhutan
  • Year and Date: 20121212-20121212
  • Invited
• [Presentation] Management of secondry glaucoma in uveitis. (2012)
  • Author(s): Ohno S, Chin S.
  • Organizer: Ophthalmology Seminar
  • Place of Presentation: Thimpu National Referral Hospital: Thimpu, Bhutan
  • Year and Date: 20121212-20121212
  • Invited
• [Presentation] Amelioration of endotoxin-induced uveitis treated with an IkappaB kinase beta inhibitor (2012)
  • Author(s): Kitaichi N, Lennikov A, Namba K, Noda K, Kanda A, Ando R, Dong Z, Fukuhara J, Kinoshita S, Ohno S, Ishida S.
  • Organizer: 8th International Symposium on Uveitis
  • Place of Presentation: Sani(Sani Beach Resort), Greece
  • Year and Date: 20121019-20121022
• [Presentation] From autoimmunity to autoinflammation in the immunopathogenesis of Behcet's disease. (2012)
  • Author(s): Ohno S.
  • Organizer: 2012 Seoul National University-Hokkaido University Joint Symposium in Ophthalmology
  • Place of Presentation: Sapporo(Hokkaido University), Japan
  • Year and Date: 20121019-20121019
  • Invited
• [Presentation] Epidemiology and genetics of Behcet's disease. (2012)
  • Author(s): Ohno S.
  • Organizer: Bechet’s Disease Symposium; How to differentiate Behcet's disease from other types of uveitis.
  • Place of Presentation: Sani(Sani Beach Resort), Greece
  • Year and Date: 20121019-20121019
  • Invited
• [Presentation] Silk route disease: epidemiology and genetics. (2012)
  • Author(s): Ohno S.
  • Organizer: International meeting of collaborative studies on Behcet’s disease and other uveitis entities
  • Place of Presentation: Rome（ローマ大学）, Italy
  • Year and Date: 20121016-20121016
  • Invited
• [Presentation] Anti-TNFα therapy for intractable uveoretinitis in Behcet's disease. (2012)
  • Author(s): Ohno S.
  • Organizer: 15th International Conference on Behcet's Disease
  • Place of Presentation: Yokohama（ﾊﾟｼﾌｨｺ横浜）, Japan
  • Year and Date: 20120714-20120714
  • Invited
• [Presentation] Amelioration of experimental autoimmune uveoretinitis by inhibiton of Glyceraldehide-derived AGEs formation (2012)
  • Author(s): Kitaichi N, Dong Z, Iwata D, Takeuchi M, Namba K, Noda K, Kanda A, Iwabuchi K, Yamagishi S, Ohno S, Ishida S.
  • Organizer: 15th International Conference on Behcet's Disease
  • Place of Presentation: ﾊﾟｼﾌｨｺ横浜、 Yokohama, Japan
  • Year and Date: 20120713-20120715
• [Presentation] Amelioration of endotoxin-induced uveitis treated with IMD-0354, an IkappaB inhibitor (2012)
  • Author(s): Lennikov A, Kitaichi N, Noda K, Ando R, Dong Z, Namba K, Ohno S, Ishida S.
  • Organizer: 15th International Conference on Behcet's Disease
  • Place of Presentation: ﾊﾟｼﾌｨｺ横浜、 Yokohama, Japan
  • Year and Date: 20120713-20120715
• [Presentation] Correlation between development of antinuclear antibody titre and decreased therapeutic efficacy in the treatment of Behçet’s disease with infliximab (2012)
  • Author(s): Namba K, Iwata D, Mizuuchi K, Kitaichi N, Kase S, Takemoto Y, Ohno S, Ishida S.
  • Organizer: 15th International Conference on Behcet's Disease
  • Place of Presentation: ﾊﾟｼﾌｨｺ横浜、 Yokohama, Japan
  • Year and Date: 20120713-20120715
• [Presentation] Effects of Infliximab Therapy in Behcet's disease (2012)
  • Author(s): Takemoto Y, Namba K, Kitaichi N, Mizuuchi K, Ohno S,
  • Organizer: 15th International Conference on Behcet's Disease
  • Place of Presentation: ﾊﾟｼﾌｨｺ横浜、 Yokohama, Japan
  • Year and Date: 20120713-20120715
• [Presentation] Diagnosis and treatment of allergic conjuctivitis. (2012)
  • Author(s): Ohno S.
  • Organizer: 16th Afro Asian Congress of Ophthalmology
  • Place of Presentation: Istanabul（HARBIYE MILITARY MUSEUM）, Turkey
  • Year and Date: 20120615-20120615
  • Invited
• [Presentation] Genome variability of human adenovirus type 8 causing epidemic keratoconjunctivitis in Japan (2012)
  • Author(s): Kitaichi N, Aoki K, Jin XH, Kaneko H, Gonzalez G, Yawata N, Koyanagi KO, Watanabe H, Ishida S, Ohno S.
  • Organizer: 10th International Adenovirus Meeting
  • Place of Presentation: Umea University, Sweden
  • Year and Date: 20120613-20120617
• [Presentation] Epidemic keratoconjunctivitis (EKC) caused by human adenovirus in Hungary (2012)
  • Author(s): Pantó L, Gonzalez G, Koyanagi KO, Pankovics P, Reuter G, Kitaichi N, Ishida S, Ohno S, Aoki K, Watanabe H.
  • Organizer: 10th International Adenovirus Meeting
  • Place of Presentation: Umea University, Sweden
  • Year and Date: 20120613-20120617
• [Presentation] Serum and salivary levels of bioactive antimicrobial peptide LL-37 in Behçet's disease and other ocular inflammatory diseases (2012)
  • Author(s): Isogai E, Kuroda K, Seki S, Kitaichi N, Namba K, Ohno S, Yoneyama H, Isogi H.
  • Organizer: 3rd International Symposium on Antimicrobial Peptides
  • Place of Presentation: Lille(Villeneuve d'Ascq), France
  • Year and Date: 20120613-20120615
• [Presentation] Ocular lesions in Behcet’s disease. (2012)
  • Author(s): Ohno S.
  • Organizer: 16th Afro Asian Congress of Ophthalmology
  • Place of Presentation: Istanabul（HARBIYE MILITARY MUSEUM）, Turkey
  • Year and Date: 20120613-20120613
  • Invited
• [Presentation] Amelioration of experimental autoimmune uveoretinitis by inhibiton of toxic AGEs formation (2012)
  • Author(s): Dong Z, Kitaichi N, Iwata D, Ando R, Fukuhara J, Lennikov A, Kanda A, Noda K, Ohno S, Ishida S.
  • Organizer: ARVO (Association for Research in Vision and Ophthalmology) Annual Meeting
  • Place of Presentation: Greater Fort Lauderdale／Broward County convention Center, USA
  • Year and Date: 20120506-20120510
• [Presentation] Amelioration of endotoxin-induced uveitis treated with an IKB kinase inhibitor, IMD-0354 in rats (2012)
  • Author(s): Lennikov A, Kitaichi N, Noda K, Ando R, Dong Z, Namba K, Ohno S, Ishida S.
  • Organizer: ARVO (Association for Research in Vision and Ophthalmology) Annual Meeting
  • Place of Presentation: Greater Fort Lauderdale／Broward County convention Center, USA
  • Year and Date: 20120506-20120510
• [Presentation] Epidemiology of allergic conjunctival diseases in Japan. (2012)
  • Author(s): Ohno S.
  • Organizer: 1st Conference on the Tear Film and Ocular Surface in Asia:
  • Place of Presentation: Kamakura（Kenchoji), Japan
  • Year and Date: 20120404-20120404
  • Invited