Analysis of humoral immune response in experimental autoimmune pancreatitis in mice.

Abstract

OBJECTIVES:

To study the autoimmune response in MRL/Mp mice, which spontaneously develop pancreatitis in the exocrine pancreatic tissue.

METHODS:

Six-week-old female mice were injected intraperitoneally with polyinosinic polycytidylic acid at a dose of 5 mg/kg of body weight twice a week for up to 12 weeks. The mice were serially killed, and the severity of their pancreatitis was graded with a histological scoring system. Immunohistological examinations were performed, and the serum levels of autoantibodies were measured by enzyme-linked immunosorbent assay.

RESULTS:

The administration of polyinosinic polycytidylic acid accelerated the development of pancreatitis, with abundant infiltration of B220 B cells and CD138 plasmacytes. Various autoantibodies directed against autoantigens, including carbonic anhydrase II and lactoferrin, were detected but none against glutamic acid decarboxylase. Of these, autoantibodies directed against the pancreatic secretory trypsin inhibitor (PSTI; 91.7%) were more prevalent than those against carbonic anhydrase II (33.3%) or lactoferrin (45.8%). Determination of the epitope of the anti-PSTI antibody showed that most immunoreactivity was directed at the site on PSTI that is active in the suppression of trypsin activity.

CONCLUSIONS:

The autoimmune response to PSTI protein may induce a failure of PSTI activity, resulting in the activation of trypsinogen and the subsequent disease progression.

• Authors: Masanori Asada, Akiyoshi Nishio, Takuji Akamatsu, Junya Tanaka, Kazuyuki Saga, Masahiro Kido, Norihiko Watanabe, Kazushige Uchida, Toshiro Fukui, Kazuichi Okazaki, Tsutomu Chiba
• Journal: Pancreas (Pancreas) Vol. 39 Issue 2 Pg. 224-31 (Mar 2010) ISSN: 1536-4828 [Electronic] United States
• PMID: 19812526 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Immunoglobulin G
• Sdc1 protein, mouse
• Syndecan-1
• Trypsin Inhibitor, Kazal Pancreatic
• Leukocyte Common Antigens
• Lactoferrin
• Carbonic Anhydrase II
• Poly I-C

Topics

• Animals
• Autoantibodies (blood)
• Autoimmune Diseases (chemically induced, immunology, pathology)
• B-Lymphocytes (immunology)
• Carbonic Anhydrase II (immunology)
• Disease Models, Animal
• Disease Progression
• Enzyme-Linked Immunosorbent Assay
• Epitope Mapping
• Female
• Immunity, Humoral
• Immunoglobulin G (blood)
• Immunohistochemistry
• Lactoferrin (immunology)
• Leukocyte Common Antigens (analysis)
• Mice
• Mice, Inbred C57BL
• Pancreas (immunology, pathology)
• Pancreatitis (chemically induced, immunology, pathology)
• Plasma Cells (immunology)
• Poly I-C
• Syndecan-1 (analysis)
• Trypsin Inhibitor, Kazal Pancreatic (immunology)