Analysis of macrophages in Adult onset Still's disease

• Project/Area Number: 26713036
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Yokohama City University
• Principal Investigator: KIRINO Yohei 横浜市立大学, 医学部, 講師 (50468154)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000); Fiscal Year 2017: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
• Keywords: ベーチェット病 / マクロファージ / ERAP1 / CCR1 / IL-10 / ゲノムワイド関連解析 / 脊椎関節炎 / EARP1 / GWAS / 遺伝子相互作用 / HLA Class I / HLA-Class I / ＥＲＡＰ１ / ペプチド / ＨＬＡ / 乾癬 / 強直性脊椎炎 / ＨＬＡ Class I / SNP / 内科 / 免疫学 / 遺伝学

Outline of Final Research Achievements

In the current study, we have evaluated the ERAP1 allotype in Turkish population. We identified 10 distinct ERAP1 allotypes. Among them, only hap10 conferred strong risk for BD. Hap 10 and HLA-B51 showed significant gene-gene interaction. Expression analysis of CCR1 and IL10 showed high expression of these molecules in M2 macrophages. Skin regions of BD patients showed M1-macrophage predominant inflammation. These results show promise for targeting GWAS-identified genes for treatment strategy for BD.

Research Products

• [Int'l Joint Research] National Institutes of Healthy(米国)
• [Int'l Joint Research] Istanbul University(トルコ)
• [Journal Article] Dysregulated heme oxygenase-1low M2-like macrophages augment lupus nephritis via Bach1 induced by type I interferons (2018)
  • Author(s): Kishimoto Daiga、Kirino Yohei、Tamura Maasa、Takeno Mitsuhiro、Kunishita Yosuke、Takase-Minegishi Kaoru、Nakano Hiroto、Kato Ikuma、Nagahama Kiyotaka、Yoshimi Ryusuke、Igarashi Kazuhiko、Aoki Ichiro、Nakajima Hideaki
  • Journal Title: Arthritis Research & Therapy Volume: 20 Issue: 1 Pages: 64-64
  • DOI: 10.1186/s13075-018-1568-1
  • Peer Reviewed / Open Access
• [Journal Article] The ocular involvement did not accompany with the genital ulcer or the gastrointestinal symptoms at the early stage of Behçet's disease (2018)
  • Author(s): Suwa A, Horita N, Ishido T, Takeuchi M, Kawagoe T, Shibuya E, Yamane T, Hayashi T, Meguro A, Ishido M, Minegishi K, Yoshimi R, Kirino Y, Kato S, Arimoto J, Fukumoto T, Ishigatsubo Y, Kurosawa M, Kaneko T, Takeno M, Mizuki N
  • Journal Title: Modern Rheumatology Volume: 27 Issue: 2 Pages: 1-17
  • DOI: 10.1080/14397595.2018.1457424
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] GWAS-identified CCR1 and IL10 loci contribute to M1-macrophage predominant inflammation in Behcet's disease. (2018)
  • Author(s): Nakano H, Yohei Kirino et al,
  • Journal Title: Arthritis Res Ther Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Dysfunction of TRIM21 in interferon signature of systemic lupus erythematosus (2018)
  • Author(s): Kamiyama Reikou、Yoshimi Ryusuke、Takeno Mitsuhiro、Iribe Yasuhiro、Tsukahara Toshinori、Kishimoto Daiga、Kunishita Yosuke、Sugiyama Yumiko、Tsuchida Naomi、Nakano Hiroto、Minegishi Kaoru、Tamura Maasa、Asami Yukiko、Kirino Yohei、Ishigatsubo Yoshiaki、Ozato Keiko、Nakajima Hideaki
  • Journal Title: Modern Rheumatology Volume: 28 Issue: 6 Pages: 993-1003
  • DOI: 10.1080/14397595.2018.1436028
  • Peer Reviewed
• [Journal Article] The predictive prognostic factors for polymyositis/dermatomyositis-associated interstitial lung disease (2018)
  • Author(s): Sugiyama Yumiko、Yohei Kirino et al,
  • Journal Title: Arthritis Research & Therapy Volume: 20 Issue: 1 Pages: 7-7
  • DOI: 10.1186/s13075-017-1506-7
  • Peer Reviewed / Open Access
• [Journal Article] Beneficial use of serum ferritin and heme oxygenase-1 as biomarkers in adult-onset Still's disease: A multicenter retrospective study. (2018)
  • Author(s): Kirino Y, Kawaguchi Y, Tada Y, Tsukamoto H, Ota T, Iwamoto M, Takahashi H, Nagasawa K, Takei S, Horiuchi T, Ichida H, Minota S, Ueda A, Ohta A, Ishigatsubo Y.
  • Journal Title: Mod Rheumatol Volume: 印刷中 Issue: 5 Pages: 1-7
  • DOI: 10.1080/14397595.2017.1422231
  • Peer Reviewed
• [Journal Article] Clinical manifestations of Behçet's disease depending on sex and age: results from Japanese nationwide registration (2017)
  • Author(s): Ishido T, Horita N, Takeuchi M, Kawagoe T, Shibuya E, Yamane T, Hayashi T, Meguro A, Ishido M, Minegishi K, Yoshimi R, Kirino Y, Kato S, Arimoto J, Ishigatsubo Y, Takeno M, Kurosawa M, Kaneko T, Mizuki N
  • Journal Title: Rheumatology Volume: 1;56(11) Issue: 11 Pages: 1918-27
  • DOI: 10.1093/rheumatology/kex285
  • Peer Reviewed / Open Access
• [Journal Article] Distinct clinical features between acute and chronic progressive parenchymal neuro-Behcet disease: meta-analysis. (2017)
  • Author(s): Ishido M, Horita N, Takeuchi M, Shibuya E, Yamane T, Kawagoe T, Ishido T, Minegishi K, Yoshimi R, Kirino Y, Hirohata S, Ishigatsubo Y, Takeno M, Kaneko T, Mizuki N
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 10196-10196
  • DOI: 10.1038/s41598-017-09938-z
  • Peer Reviewed / Open Access
• [Journal Article] Diagnostic test accuracy of ultrasound for synovitis in rheumatoid arthritis: systematic review and meta-analysis. (2017)
  • Author(s): Takase-Minegishi K, Horita N, Kobayashi K, Yoshimi R, Kirino Y, Ohno S, Kaneko T, Nakajima H, Wakefield RJ, Emery P.
  • Journal Title: Rheumatology (Oxford). Volume: 印刷中 Issue: 1 Pages: 49-58
  • DOI: 10.1093/rheumatology/kex036
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Musculoskeletal ultrasonography delineates ankle symptoms in rheumatoid arthritis. (2017)
  • Author(s): Toyota Y, Tamura M, Kirino Y, Sugiyama Y, Tsuchida N, Kunishita Y, Kishimoto D, Kamiyama R, Miura Y, Minegishi K, Yoshimi R, Ueda A, Nakajima H.
  • Journal Title: Mod Rheumatol. Volume: 27 Issue: 3 Pages: 425-429
  • DOI: 10.1080/14397595.2016.1222650
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Dense genotyping of immune-related loci implicates host responses to microbial exposure in Beh?et's disease susceptibility (2017)
  • Author(s): Takeuchi Masaki、Yohei Kirino et al,
  • Journal Title: Nature Genetics Volume: 49 Issue: 3 Pages: 438-443
  • DOI: 10.1038/ng.3786
  • Peer Reviewed
• [Journal Article] Continuous evolution of clinical phenotype in 578 Japanese patients with Behcet's disease: a retrospective observational study. (2016)
  • Author(s): Kirino Y, Ideguchi H, Takeno M, Suda A, Higashitani K, Kunishita Y, Takase-Minegishi K, Tamura M, Watanabe T, Asami Y, Uehara T, Yoshimi R, Yamazaki T, Sekiguchi A, Ihata A, Ohno S, Ueda A, Igarashi T, Nagaoka S, Ishigatsubo Y, Nakajima H.
  • Journal Title: Arthritis Res Ther Volume: 2016 Issue: 1 Pages: 217-217
  • DOI: 10.1186/s13075-016-1115-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A single endoplasmic reticulum aminopeptidase-1 protein allotype is a strong risk factor for Behcet's disease in HLA-B*51 carriers. (2016)
  • Author(s): Takeuchi M, Ombrello MJ, Kirino Y, Erer B, Tugal-Tutkun I, Seyahi E, Ozyazgan Y, Watts NR, Gul A, Kastner DL, Remmers EF.
  • Journal Title: Ann Rheum Dis Volume: 75 Issue: 12 Pages: 2208-2211
  • DOI: 10.1136/annrheumdis-2015-209059
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] ERAP1 (2016)
  • Author(s): 桐野洋平
  • Journal Title: 炎症と免疫 Volume: 24 Pages: 5-5
• [Journal Article] A polymorphism in CCR1/CCR3 is associated with narcolepsy. (2015)
  • Author(s): Toyoda H, Miyagawa T, Koike A, Kanbayashi T, Imanishi A, Sagawa Y, Kotorii N, Kotorii T, Hashizume Y, Ogi K, Hiejima H, Kamei Y, Hida A, Miyamoto M, Imai M, Fujimura Y, Tamura Y, Ikegami A, Wada Y, Moriya S, Furuya H, Takeuchi M, Kirino Y, Meguro A, Remmers EF, Kawamura Y, Otowa T, Miyashita A, et al.
  • Journal Title: Brain Behav Immun. Volume: 印刷中 Pages: 148-155
  • DOI: 10.1016/j.bbi.2015.05.003
  • Peer Reviewed
• [Journal Article] Takayasu arteritis and ulcerative colitis -high concurrence ratio and genetic overlap. (2015)
  • Author(s): Terao C, Matsumura T, Yoshifuji H, Kirino Y, Maejima Y, Kochi Y, Ogimoto A, Yamamoto M, Takahashi H, Nakayamada S, Saito K, Wada Y, Narita I, Kawaguchi Y, Yamanaka H, Ohmura K, Atsumi T, Tanemoto K, Miyata T, Kuwana M, Komuro I, Tabara Y, Ueda A, Isobe M, Mimori T, Matsuda F.
  • Journal Title: Arthritis Rheumatol. Volume: - Issue: 8 Pages: 2226-2232
  • DOI: 10.1002/art.39157
  • Peer Reviewed
• [Journal Article] Genetic architectures of seropositive and seronegative rheumatic diseases. (2015)
  • Author(s): Kirino Y, Remmers EF.
  • Journal Title: Nat Rev Rheumatol Volume: 11 Issue: 7 Pages: 401-14
  • DOI: 10.1038/nrrheum.2015.41
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 成人スティル病 (2018)
  • Author(s): 桐野洋平
  • Organizer: 日本リウマチ学会総会
  • Int'l Joint Research / Invited
• [Presentation] ベーチェット病の遺伝学を用いた最適化医療 (2018)
  • Author(s): 桐野洋平
  • Organizer: 日本リウマチ学会総会
  • Int'l Joint Research / Invited
• [Presentation] Use of Including Serum Ferritin and Heme Oxygenase 1 in the Yamaguchi’s Classification for Adult-Onset Still’s Disease: A Multicenter Retrospective Study (2017)
  • Author(s): Yohei Kirino
  • Organizer: 米国リウマチ学会総会
  • Int'l Joint Research
• [Presentation] 単一のERAP1アロタイプがHLA-B*51を保有したベーチェット病患者のリスクとなる (2016)
  • Author(s): Yohei Kirino,Elaine F Remmers,Masaki Takeuchi, Michael J Ombrello,Burak Erer,Ilknur Tugal-Tutkun,Emire Seyahi,Yilmaz Ozyazgan,Ahmet Gul,Daniel L Kastner
  • Organizer: 日本リウマチ学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-04-21
  • Int'l Joint Research
• [Presentation] Functional analysis of macrophages in Behcet's disease (2016)
  • Author(s): Hiroto Nakano,Yohei Kirino,Kana Higashitani,Mitsuhiro Takeno,Ryusuke Yoshimi,Yoshiaki Ishigatsubo,Atsuhisa Ueda
  • Organizer: 日本リウマチ学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-04-21
  • Int'l Joint Research
• [Presentation] 日本人ベーチェット病の臨床像の変化：584例の解析 (2016)
  • Author(s): 東谷 佳奈,桐野 洋平,出口 治子,須田 昭子,杉山 裕美子,土田 奈緒美,國下 洋輔,神山 玲光,渡邉 俊幸,上原 武晃,峯岸 薫,浜 真麻,吉見 竜介,山崎 哲,浅見 由希子,関口 章子,井畑 淳,岳野 光洋,大野 滋,五十嵐 俊久,長岡 昇平,石ヶ坪 良明,上田 敦久
  • Organizer: 日本リウマチ学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-04-21
  • Int'l Joint Research
• [Presentation] ベーチェット病特殊病型の診断の問題点：590例の解析 (2016)
  • Author(s): 桐野 洋平,出口 治子,須田 昭子,杉山 裕美子,土田 奈緒美,國下 洋輔,神山 玲光,渡邉 俊幸,上原 武晃,峯岸 薫,浜 真麻,吉見 竜介,山崎 哲,浅見 由希子,関口 章子,井畑 淳,岳野 光洋,大野 滋,五十嵐 俊久,長岡 昇平,石ヶ坪 良明,上田 敦久
  • Organizer: 日本リウマチ学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-04-21
  • Int'l Joint Research
• [Presentation] Functional analysis of macrophages in Behcet's disease (2015)
  • Author(s): Nakano H, Kirino Y, et al
  • Organizer: ISSAID 2015
  • Place of Presentation: Hilton Dresden(ドレスデン、ドイツ）
  • Year and Date: 2015-10-01
  • Int'l Joint Research
• [Presentation] 単一のERAP1アロタイプがHLA-B*51を保有したベーチェット病患者のリスクとなる (2015)
  • Author(s): 桐野洋平, et al
  • Organizer: 第60回日本リウマチ学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-04-21
  • Int'l Joint Research
• [Book] リウマチ病学テキスト改訂第2版 (2017)
  • Author(s): 桐野洋平
  • Total Pages: 3
  • Publisher: 診断と治療社