title: Pathogenicity of IgG in patients with IgG4-related disease.
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.
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shiokawa
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Kodama
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Kuriyama
authors.affiliation: Translational Research Center, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Teruko
authors.initials: T
authors.lastname: Tomono
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Morita
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kakiuchi
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Matsumori
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mima
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishikawa
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Ueda
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Tsuda
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamauchi
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ryuki
authors.initials: R
authors.lastname: Minami
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Sakuma
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ota
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Maruno
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kurita
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yugo
authors.initials: Y
authors.lastname: Sawai
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Tsuji
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Uza
authors.affiliation: Department of Gastroenterology and Hepatology, Shiga Medical Center for Adults, Shiga, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Matsumura
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Okayama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Notohara
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tsuruyama
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Seno
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000097:blood; D008297:Male; D051379:Mice; D010179:Pancreas / Q000276:immunology / Q000473:pathology; D010195:Pancreatitis / Q000276:immunology / Q000473:pathology; D012469:Salivary Glands / Q000276:immunology / Q000473:pathology
chemical_list: D007074:Immunoglobulin G
keywords: CHRONIC PANCREATITIS; IMMUNOLOGY; PANCREATIC DISEASE; PANCREATIC PATHOLOGY