Pathogenicity and antigen of IgG4 antibody in patients with IgG4 related disease

• Project/Area Number: 26893123
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: Shiokawa Masahiro 京都大学, 医学(系)研究科(研究院), 医員 (50737880)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: ＩｇＧ４ / 自己免疫性膵炎 / ＩｇＧ４関連疾患 / IgG4 / 抗原 / 病原性 / IgG4関連疾患

Outline of Final Research Achievements

Objective: The pathogenic roles of IgGs, including IgG4, in patients with IgG4-RD remain unknown. Design: We examined the pathogenic activity of circulating IgGs in patients with IgG4-RD by injecting their IgGs into neonatal Balb/c mice. Binding of patients’ IgGs to pancreatic tissues was also analyzed in an ex vivo mouse organ culture model and in tissue samples of patients with autoimmune pancreatitis (AIP). Results: Subcutaneous injection of patients’ IgG, but not control IgG, induced pancreatic and salivary gland injuries. Pancreatic injury was also induced by injecting patients’ IgG1 or IgG4, with more destructive change induced by IgG1 than by IgG4. The potent pathogenic activity of patients’ IgG1 was significantly inhibited by simultaneous injection of patients’IgG4.
Conclusions: IgG1 and IgG4 from patients with IgG4-RD have pathogenic activities through binding to affected tissues in neonatal mice.

Research Products

• [Journal Article] Pathogenicity of Immunoglobulin G in Patients with IgG4-related Disease. (2016)
  • Author(s): Shiokawa M, Kodama Y, Kuriyama K, Yoshimura K, Tomono T, Morita T, Kakiuchi N, Matsumori T, Mima A, Nishikawa Y, Ueda T, Tsuda M, Yamauchi Y, Minami R, Sakuma Y, Ota Y, Maruno T, Kurita A, Sawai Y, Tsuji Y, Uza N, Matsumura K, Watanabe T, Notohara K, Tsuruyama T, Seno H, Chiba T.
  • Journal Title: Gut Volume: 未定 Issue: 8 Pages: 3292-3301
  • DOI: 10.1136/gutjnl-2015-310336
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Pathogenic Role of IgG in Patients with IgG4-related Disease on Neonatal Mice (2016)
  • Author(s): Shiokawa M, Kodama Y, Kuriyama K, Yoshimura K, Tomono T, Morita T, Kakiuchi N, Matsumori T, Mima A, Nishikawa Y, Ueda T, Tsuda M, Yamauchi Y, Minami R, Sakuma Y, Ota Y, Maruno T, Kurita A, Sawai Y, Tsuji Y, Uza N, Matsumura K, Watanabe T, Notohara K, Tsuruyama T, Seno H, Chiba T.
  • Organizer: DDW
  • Place of Presentation: San Diego
  • Year and Date: 2016-05-21
  • Int'l Joint Research
• [Presentation] IgG4関連疾患におけるIgGの病原性と標的抗原の解明 (2016)
  • Author(s): 塩川 雅広、児玉 裕三、妹尾 浩、千葉 勉
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2016-04-21
• [Presentation] 自己免疫性膵炎患者のIgGの病原性 (2015)
  • Author(s): 塩川雅広
  • Organizer: 厚生労働科学研究委託費 難治性疾患等実用化研究事業 IgG4関連疾患の病態解明と新規治療法の確立に関する研究 平成 26 年度 第１回 班会議
  • Place of Presentation: 京都市左京区芝蘭会館
  • Year and Date: 2015-01-10
• [Book] 膵臓 (2015)
  • Author(s): 塩川雅広
  • Total Pages: 6
  • Publisher: 日本膵臓学会
• [Book] IgG4関連疾患アトラス (2015)
  • Author(s): 塩川雅広
  • Total Pages: 6
  • Publisher: 前田書店