Amylase α-2A Autoantibodies Novel Marker of Autoimmune Pancreatitis and Fulminant Type 1 Diabetes

OBJECTIVE-The pathogenesis of autoimmune pancreatitis (AIP) and fulminant type I diabetes remains unclear, although it is known that immune-mediated processes severely compromise the endocrine and exocrine functions in both diseases. RESEARCH DESIGN AND METHODS-We have screened a lambda Trip1Ex2 human pancreas cDNA library with serum from a patient with AIP and obtained positive clones. Sequence analysis revealed that 7 of 10 clones were identical to human amylase alpha-2A. Using a recombinant COOH-terminal amylase alpha-2A protein, we developed an enzyme-linked immunosorbent assay system to detect autoantibodies against human amylase alpha-2A. RESULTS-All 15 serum samples from patients with All? recognized the recombinant protein, whereas sera from 25 patients with chronic alcoholic pancreatitis and sera from 25 patients with a pancreas tumor did not. Interestingly, 88% (15/17) of patients with fulminant type 1 diabetes were positive for an autoantibody against amylase alpha-2A. These antibodies were detected in 21% of patient's with acute-onset type I diabetes (9 of 42) and 6% of type 2 diabetic patients (4 of 67). CONCLUSIONS-These results suggest that an autoantibody against amylase alpha-2A is a novel diagnostic marker for both AIP and fulminant type I diabetes and that, clinically and immunologically, AIP and fulminant type 1 diabetes are closely related. Diabetes 58:732-737, 2009