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

Objective: The pathogenesis of autoimmune pancreatitis (AIP) and fulminant type 1 diabetes (FT1DM) remains unclear, although it is known that immune-mediated processes severely compromise the endocrine and exocrine functions in both diseases. Methods: We have screened a λTriplEx2 human pancreas cDNA library with serum from a patient with AIP and obtained positive clones. Sequence analysis revealed that seven out of 10 clones were identical to human amylase α-2A. Using a recombinant C-terminal amylase α-2A protein, we developed an enzyme-linked immunosorbent assay system to detect autoantibodies against human amylase α-2A. Results: All 15 serum samples from patients with AIP recognized the recombinant protein, while 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 FT1DM were positive for an autoantibody against amylase α-2A. These antibodies were detected in 21% of patients with acute-onset type 1 diabetes (AT1DM, 9/42) and 6% of type 2 diabetic patients (4/67). Conclusions: These results suggest that an autoantibody against amylase α-2A is a novel diagnostic marker for both AIP and FT1DM, and that clinically and immunologically, AIP and FT1DM are closely related.