Article Text

PDF
Original article
Pathogenicity of IgG in patients with IgG4-related disease
  1. Masahiro Shiokawa1,
  2. Yuzo Kodama1,
  3. Katsutoshi Kuriyama1,
  4. Kenichi Yoshimura2,
  5. Teruko Tomono1,
  6. Toshihiro Morita1,
  7. Nobuyuki Kakiuchi1,
  8. Tomoaki Matsumori1,
  9. Atsushi Mima1,
  10. Yoshihiro Nishikawa1,
  11. Tatsuki Ueda1,
  12. Motoyuki Tsuda1,
  13. Yuki Yamauchi1,
  14. Ryuki Minami1,
  15. Yojiro Sakuma1,
  16. Yuji Ota1,
  17. Takahisa Maruno1,
  18. Akira Kurita1,
  19. Yugo Sawai1,
  20. Yoshihisa Tsuji1,
  21. Norimitsu Uza1,
  22. Kazuyoshi Matsumura3,
  23. Tomohiro Watanabe1,
  24. Kenji Notohara4,
  25. Tatsuaki Tsuruyama5,
  26. Hiroshi Seno1,
  27. Tsutomu Chiba1
  1. 1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
  2. 2Translational Research Center, Kyoto University Hospital, Kyoto, Japan
  3. 3Department of Gastroenterology and Hepatology, Shiga Medical Center for Adults, Shiga, Japan
  4. 4Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Okayama, Japan
  5. 5Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan
  1. Correspondence to Dr Yuzo Kodama Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; kodamayu{at}kuhp.kyoto-u.ac.jp

Abstract

Objective IgG4-related disease (IgG4-RD) is a systemic disease characterised by elevated serum IgG4 and IgG4-positive lymphoplasmacytic infiltration in the affected tissues. The pathogenic role of IgGs, including IgG4, in patients with IgG4-RD, however, is unknown.

Design We examined the pathogenic activity of circulating IgGs in patients with IgG4-RD by injecting their IgGs into neonatal male Balb/c mice. Binding of patient IgGs to pancreatic tissue was also analysed in an ex vivo mouse organ culture model and in tissue samples from patients with autoimmune pancreatitis (AIP).

Results Subcutaneous injection of patient IgG, but not control IgG, resulted in pancreatic and salivary gland injuries. Pancreatic injury was also induced by injecting patient IgG1 or IgG4, with more destructive changes induced by IgG1 than by IgG4. The potent pathogenic activity of patient IgG1 was significantly inhibited by simultaneous injection of patient IgG4. Binding of patient IgG, especially IgG1 and IgG4, to pancreatic tissue was confirmed in both the mouse model and AIP tissue samples.

Conclusions IgG1 and IgG4 from patients with IgG4-RD have pathogenic activities through binding affected tissues in neonatal mice.

  • CHRONIC PANCREATITIS
  • IMMUNOLOGY
  • PANCREATIC DISEASE
  • PANCREATIC PATHOLOGY

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles