Identification of a Novel Autoantibody Against Pancreatic Secretory Trypsin Inhibitor in Patients with Autoimmune Pancreatitis

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Abstract
Objectives: Although autoimmune pancreatitis (AIP) has been recently recognized as a new disease entity of chronic pancreatitis, the clinical diagnosis of the disease remains disputed. Autoantibodies against carbonic anhydrase II and lactoferrin are detected in most patients with AIP, but not in about 10%. We undertook this study to determine whether additional autoantibodies are present in the serum level of AIP patients. Methods: We recruited 26 patients with AIP for the study. For comparison, we also recruited 53 patients with various pancreatic diseases and 12 healthy subjects. We immunoscreened human pancreatic cDNA library using patients' sera. Positive clones were analyzed by DNA sequencing and were constructed into a pGEX-4T-1 expression vector. The recombinant proteins were used as antigens in enzyme-linked immunosorbent assay to screen the subjects' sera for autoantibodies. Results: We cloned a cDNA encoding the pancreatic secretory trypsin inhibitor (PSTI). Among 26 patients with AIP, autoantibodies against PSTI were significantly positive in 11 (42.3%) by western blotting and in 8 (30.8%) by enzyme-linked immunosorbent assay, respectively. However, none of control subjects was positive for anti-PSTI antibodies. Conclusions: These findings suggest that PSTI may be related to the pathogenesis of AIP, and autoantibodies against PSTI can be a useful diagnostic marker for the disease. Abbreviations: AIP - autoimmune pancreatitis, PSTI - pancreatic secretory trypsin inhibitor, CA-II - carbonic anhydrase II, LF - lactoferrin, TBST - Tris-buffered saline containing 0.05% Tween 20, SDS-PAGE - sodium dodecyl sulfate-polyacrylamide gel electrophoresis, ELISA-enzyme-linked immunosorbent assay, OD - optical density, ANA - antinuclear antibody, AMA - antimitochondrial antibody, RF - rheumatoid factor