A immunological study of target antigens in patients with autoimmune pancreatitis and animal models

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Background and aim : Although an autoimmune mechanism may be involved in autoimmune pancreatitis (AIP), the pathogenesis still remains unclear. We previously reported that autoantibodies against carbonic anhydrase II (CA-II) and lactoferrin (LF) are frequently observed in AIP patients. However, approximately 10 % of patients with AIP show negative antibodies against CA-II or LF. The aim of this study is to find novel autoantibodies in AIP. Subjects : Twenty-six patients with AIP, 10 patients with alcoholic chronic pancreatitis, 10 patients with idiopathic chronic pancreatitis, 17 patients with acute pancreatitis, 16 patients with pancreatic cancer, and 12 normal subjects as control were recruited for the study. Methods : We performed the immuno-screening using human pancreatic cDNA library and patients' sera. Positive clones were analyzed by DNA sequencing, and constructed into the expression vector pGEX-4T-1. The recombinant proteins were expressed as glutathione S-transferase fusion protein in E.coli. The serum levels of the newly identified autoantibody were measured by enzyme linked immunosorbent assay. Results : We cloned a cDNA encoding entire coding sequence of the human pancreatic secretory trypsin inhibitor (PSTI) cDNA by the immuno-screening. Serum levels of anti-human PSTI antibody were increased in 30.8% (8/26) of AIP patients in comparison with those in alcoholic chronic pancreatitis, idiopathic chronic pancreatitis, acute pancreatitis, pancreatic cancer, and in normal subjects. Conclusions : Anti-human PSTI antibody, a novel autoantibody with AIP, may be involved in the pathophysiology and useful as a diagnostic marker in patients with AIP.