Sensitization to and Challenge with Gliadin Induce Pancreatitis and Extrapancreatic Inflammation in HLA-DQ8 Mice: An Animal Model of Type 1 Autoimmune Pancreatitis.
OBJECTIVE
The aim of this study was to establish a pathogenetic mechanism of pancreatitis in celiac disease and IgG4-related disease using gluten-sensitive human leukocyte antigen (HLA)-DQ8 transgenic mice.


METHODS
Transgenic mice expressing HLA-DQ8 genes were utilized. Control mice were not sensitized but were fed gliadin-free rice cereal. Experimental groups consisted of gliadin-sensitized and gliadin-challenged mice; nonsensitized mice with cerulein hyperstimulation; and gliadin-sensitized and gliadinchallenged mice with cerulein hyperstimulation.


RESULTS
Gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation showed significant inflammatory cell infiltrates, fibrosis and acinar atrophy compared with the control mice and the other experimental groups. The immunohistochemical analysis showed greater IgG1-positive plasma cells in the inflammatory infiltrates of gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation compared with the control mice and the other experimental groups. Gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation or gliadin-sensitized and gliadinchallenged mice showed IgG1-stained inflammatory cell infiltrates in the extrapancreatic organs, including the bile ducts, salivary glands, kidneys, and lungs.


CONCLUSIONS
Gliadinsensitization and cerulein hyperstimulation of gluten-sensitive HLA-DQ8 transgenic mice resulted in pancreatitis and extrapancreatic inflammation. This animal model suggests that chronic gliadin ingestion in a susceptible individual with the HLA-DQ8 molecule may be associated with pancreatitis and extrapancreatic inflammation.
Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.
Sung-Hoon
SH
Moon
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Jihun
J
Kim
Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
Mi-Young
MY
Kim
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Do Hyun
do H
Park
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Tae Jun
TJ
Song
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Sun A
SA
Kim
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Sang Soo
SS
Lee
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Dong Wan
DW
Seo
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Sung Koo
SK
Lee
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Myung-Hwan
MH
Kim
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002108:Ceruletide / Q000276:immunology; D004195:Disease Models, Animal; D005903:Gliadin / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology*; D006967:Hypersensitivity; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010195:Pancreatitis / Q000139:chemically induced / Q000276:immunology*
D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D007074:Immunoglobulin G; D002108:Ceruletide; D005903:Gliadin
Autoimmune diseases; Celiac disease; Pancreatitis