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Pathogenicity of IgG in patients with IgG4-related disease.

Authors
  • Shiokawa, Masahiro1
  • Kodama, Yuzo1
  • Kuriyama, Katsutoshi1
  • Yoshimura, Kenichi2
  • Tomono, Teruko1
  • Morita, Toshihiro1
  • Kakiuchi, Nobuyuki1
  • Matsumori, Tomoaki1
  • Mima, Atsushi1
  • Nishikawa, Yoshihiro1
  • Ueda, Tatsuki1
  • Tsuda, Motoyuki1
  • Yamauchi, Yuki1
  • Minami, Ryuki1
  • Sakuma, Yojiro1
  • Ota, Yuji1
  • Maruno, Takahisa1
  • Kurita, Akira1
  • Sawai, Yugo1
  • Tsuji, Yoshihisa1
  • And 7 more
  • 1 Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. , (Japan)
  • 2 Translational Research Center, Kyoto University Hospital, Kyoto, Japan. , (Japan)
  • 3 Department of Gastroenterology and Hepatology, Shiga Medical Center for Adults, Shiga, Japan. , (Japan)
  • 4 Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Okayama, Japan. , (Japan)
  • 5 Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. , (Japan)
Type
Published Article
Journal
Gut
Publisher
BMJ
Publication Date
Aug 01, 2016
Volume
65
Issue
8
Pages
1322–1332
Identifiers
DOI: 10.1136/gutjnl-2015-310336
PMID: 26964842
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. 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). 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. IgG1 and IgG4 from patients with IgG4-RD have pathogenic activities through binding affected tissues in neonatal mice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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