Amylase alpha-2A autoantibodies: novel marker of autoimmune pancreatitis and fulminant type 1 diabetes.
OBJECTIVE
The pathogenesis of autoimmune pancreatitis (AIP) and fulminant type 1 diabetes 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 lambdaTriplEx2 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 AIP 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 patients with acute-onset type 1 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 1 diabetes and that, clinically and immunologically, AIP and fulminant type 1 diabetes are closely related.
Endo
Toyoshi
T
Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo City, Yamanashi, Japan. endot@yamanashi.ac.jp
Takizawa
Soichi
S
Tanaka
Shoichiro
S
Takahashi
Masashi
M
Fujii
Hideki
H
Kamisawa
Terumi
T
Kobayashi
Tetsuro
T
D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D003001:Cloning, Molecular; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D010183:Pancreatic Ducts / Q000276:immunology / Q000473:pathology; D055292:Pancreatic alpha-Amylases / Q000235:genetics / Q000276:immunology*; D010195:Pancreatitis / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000276:immunology
D001323:Autoantibodies; D017931:DNA Primers; D011994:Recombinant Proteins; C513534:AMY2A protein, human; D055292:Pancreatic alpha-Amylases