Analysis of macrophages in Adult onset Still's disease

• Project/Area Number: 15K15374
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: 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): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 成人スティル病 / マクロファージ / ヘムオキシゲナーゼ1 / フェリチン / ヘムオキシゲナーゼ / ＨＯ－１

Outline of Final Research Achievements

In the current study, we collected sera from a total of 145 AOSD patients. These AOSD' patients were further divided into active, remission, and relapse groups. Forty-six cases of systemic vasculitis, sepsis, etc. were included as disease controls. We found that serum ferritin and HO-1 levels were significantly higher in active and relapsed AOSD cases, and were reduced by the treatment. Although a significant correlation was found between serum ferritin and HO-1 levels, a discrepancy was found in some cases such as iron-deficiency anemia.ROC analysis identified optimal levels of serum ferritin (>819 ng/ml; sensitivity 76.1% and specificity 73.8%), and serum HO-1 (>30.2 ng/ml; sensitivity 84.8% and specificity 83.3%) that differentiated AOSD from controls. Interestingly, 88.9% of patients with AOSD who relapsed exceeded the cut-off value of serum HO-1, but only 50.0% exceeded serum ferritin , suggesting that serum HO-1 levels may be a convenient indicator of AOSD disease status.

Research Products

• [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] GWAS-identified CCR1 and IL10 loci contribute to M1-macrophage predominant inflammation in Behcet's disease. (2018)
  • Author(s): Nakano Hiroto, Kirino Yohei et al,
  • Journal Title: Arthritis Research & Therapy Volume: 20
  • 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] 全国膠原病友の会 (2017)
  • Author(s): 成人スティル病の概要
  • Journal Title: 全国膠原病友の会 「SSK 膠原」 Volume: 185 Pages: 28-32
• [Journal Article] 文光堂 (2016)
  • Author(s): 成人発症Still病
  • Journal Title: Medical Practice Volume: 33 Pages: 28-32
• [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] 成人スティル病における血清フェリチンとヘムオキシゲナーゼ１の診断への有用性：多施設共同研究 (2017)
  • 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] 成人スティル病における血清フェリチンとヘムオキシゲナーゼ１の診断への有用性：多施設共同研究の第2報 (2016)
  • 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: 2016-04-23
  • Int'l Joint Research
• [Presentation] 成人スティル病における血清フェリチン・ヘムオキシゲナーゼ１の診断への有用性：多施設共同研究 (2016)
  • Author(s): 桐野洋平
  • Organizer: 日本リウマチ学会総会
  • Place of Presentation: 福岡国際会議場（福岡県博多市）
  • Year and Date: 2016-04-21
  • Int'l Joint Research
• [Presentation] Use of Serum Ferritin and Heme Oxygenase 1 for the Diagnosis of Adult-Onset Still’s Disease: A Preliminary Report of Multicenter Study (2015)
  • Author(s): Kirino et al
  • Organizer: American Collage of Rheumatology Annual Meeting
  • Place of Presentation: San Fransisco, USA
  • Year and Date: 2015-11-07
  • Int'l Joint Research