Study on causes and pathophysiology of CINCA syndrome patients without CIAS1 gene mutations

• Project/Area Number: 19591249
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyoto University
• Principal Investigator: NISHIKOMORI Ryuta Kyoto University, 医学研究科, 助教 (70359800)
• Co-Investigator(Kenkyū-buntansha): 神戸 直智 千葉大学, 大学院・医学研究院, 講師 (50335254)
• Co-Investigator(Renkei-kenkyūsha): KAMBE Naotomo 千葉大学, 大学院・医学研究院, 講師 (50335254)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 小児免疫・アレルギー・膠原病学 / CINCA症候群 / CIAS1 / 体細胞モザイク / 自己炎症症候群 / 自己炎症性疾患 / NLRP3 / 体細胞モデイク

Research Abstract

蕁麻疹様の発疹、関節症状、無菌性髄膜炎を3主徴とするCINCA症候群の原因遺伝子としてCIAS1が報告されたが、約40%に同遺伝子異常を認めない。本研究でCIAS1遺伝子異常を認めない症例を集積し、4例中3例に潜在性CIAS1体細胞モザイクが存在することを示した。また同疾患患者単球はTLR4リガンドであるLPS刺激で細胞死が誘導されることを示し、同性状を用いた診断法を開発した。

Research Products

• [Journal Article] Role of NOD2 genotype in the clinical phenotype of Blau syndrome and early-onset sarcoidosis (2009)
  • Author(s): Okafuji I., R. Nishikomori, N. Kanazawa, N. Kambe, A. Fujisawa, S. Yamazaki, M. Saito, T. Yoshioka, T. Kawai, H. Sakai, H. Tanizaki, T. Heike, Y. Miyachi, T. Nakahata
  • Journal Title: Arthritis Rheum 60 Pages: 242-250
  • Peer Reviewed
• [Journal Article] Role of the NOD2 genotype in the clinical phenotype of Blau syndrome and early-onset sarcoidosis. (2009)
  • Author(s): Okafuji I, et al
  • Journal Title: Arthritis Rheum 60 Pages: 242-250
  • Peer Reviewed
• [Journal Article] Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin associated periodic syndrome patients (2008)
  • Author(s): Saito, M., R. Nishikomori, N. Kambe, A. Fujisawa, H. Tanizaki, K. Takeichi, T. Imagawa, T. Iehara, H. Takada, T. Matsubayashi, H. Tanaka, H. Kawashima, K. S. Kagami, I. Okafuji, T. Yoshioka, S. Adachi, T. Heike, Y. Miyachi, T. Nakahata
  • Journal Title: Blood 111 Pages: 2132-2141
  • Peer Reviewed
• [Journal Article] A CIAS1 mutation in a Japanese girl with familial cold autoinflammatory syndrome (2008)
  • Author(s): Kanegane H., T. Itazawa, M. Saito, R. Nishikomori, T. Makino, T. Shimizu, Y. Adachi, T. Nakahata, and T. Miyawaki
  • Journal Title: Eur J Pediatr 267 Pages: 245-247
  • Peer Reviewed
• [Journal Article] Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative (2008)
  • Author(s): Saito M, et al
  • Journal Title: Blood 111 Pages: 2132-2141
  • Peer Reviewed
• [Journal Article] Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients. (2008)
  • Author(s): Saito M, et. al.
  • Journal Title: Blood 111 Pages: 2132-2141
  • Peer Reviewed
• [Journal Article] Disease-associated mutations in CIAS1 induce cathepsin B-dependent rapid cell death of human THP-1 monocytic cells (2007)
  • Author(s): Fujisawa A., N. Kambe, M. Saito, R. Nishikomori, H. Tanizaki, N. Kanazawa, S. Adachi, T. Heike, J. Sagara, T. Suda, T. Nakahata and Y. Miyachi
  • Journal Title: Blood 109 Pages: 2903-2911
  • Peer Reviewed
• [Journal Article] Disease-associated mutations in CIAS1 induce cathepsin B-dependent rapid cell death of human THP-1 monocytic cells. (2007)
  • Author(s): Fujisawa A, et. al.
  • Journal Title: Blood 109 Pages: 2903-2911
  • Peer Reviewed
• [Journal Article] A CIAS1 mutation in a Japanese girl with familial cold autoinflammatory syndrome. (2007)
  • Author(s): Kanegane H, et. al.
  • Journal Title: Eur J Pediatr 167 Pages: 245-247
  • Peer Reviewed
• [Presentation] Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients (2007)
  • Author(s): Saito M.,R. Nishikomori, N. Kambe, A. Fujisawa, H. Tanizaki, T. Kawai, H. Sakai, I. Okafuji, T. Yoshioka, S. Adachi, T. Heike, Y. Miyachi, T. Nakahata
  • Organizer: 71st ACR annual meeting
  • Place of Presentation: Boston MA
  • Year and Date: 2007-11-10