Amylase α-2A Autoantibodies

Abstract

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. RESEARCH DESIGN AND METHODS-We have screened aTriplEx2 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 ␣-2A. Using a recombinant COOH-terminal amylase ␣-2A protein, we developed an enzyme-linked immunosorbent assay system to detect autoantibodies against human amylase ␣-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 ␣-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 ␣-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. Diabetes 58:732-737, 2009 R ecently, autoimmune pancreatitis (AIP), a unique form of chronic pancreatitis, has been reported as a discrete disease entity (1). It is characterized by 1) irregular narrowing of the main pancreatic duct and swelling of the pancreas, both of which are due to abundant lymphoplasmacytic inflammation to the exocrine pancreas (2); 2) the increased serum level of IgG and IgG4; 3) positive autoantibodies such as lactoferrin autoantibody or carbonic anhydrase II (CAII) autoantibody (3,4); and 4) a high prevalence of diabetes with complications (5).We recently reported that a high proportion of pancreatic islets and exocrine pancreatic tissues were infiltrated by CD4 ϩ or CD8 ϩ T-cells in the inflammatory process, which might induce diabetes in AIP (6). In addition, treatment with prednisolone improved insulin secretion and glycemic control in AIP patients (5). These data support the concept that autoimmune mechanism(s) plays a pivotal role in the destruction of the endocrine and exocrine pancreas in AIP patients with diabetes.Clinically, the most common initial symptom of AIP is jaundice, but in some patients, no symptoms or only mild symptoms, frequently without acute attacks of pancreatitis, may be present (7). It is difficult to distinguish AIP from other types of chronic pancreatitis or cancer of the pancreatic head (8). In such cases, detection of autoantibodies is useful for diagnosing AIP, but a proportion of patients with AIP are negative for autoantibodies against lactoferrin and CAII (3,4).We encountered an AIP patient whose serum IgG and IgG4 levels were 3,498 and 2,430 mg/dl, respectively. It has been reported that median levels (5th and 95th percentile...

Autoimmune Pancreatitis: The Emerging Role of Serologic Biomarkers

“…Interestingly, in this issue of Diabetes, Endo et al (10) report that 5 out of 15 patients with AIP were heterozygous for the HLA DRB1* 0405-DQB1*0401 haplotype, which confirms previously published results in a Japanese population (11,12). It is noteworthy that a recent study provided convincing evidence that CD4…”

Immunology of IgG4-related disease

“…Putative autoantigens have been proposed as targets of an antibody response in a proportion of patients with IgG4-related AIP and sialoadenitis [76][77][78][79][80][81][82][83]. These antigens include proteins expressed in duct epithelia (carbonic anhydrase II and IV) and in acinar cells (lactoferrin, amylase-a-2A, pancreatic trypsinogens and pancreatic secretory trypsin inhibitor).…”

Pathophysiological mechanisms involving aggressive islet cell destruction in fulminant type 1 diabetes [Review]

“…The similarity of histological findings and genetic background and the high prevalence of impaired glucose tolerance and autoantibodies against amylase suggest that autoimmune mechanisms against amylase might have some common effects on the destruction of pancreatic islets and exocrine tissues in both fulminant type 1 diabetes and autoimmune pancreatitis. Treatment with prednisolone improved insulin secretion and glycemic control and induced a rapid decrease of the titer of autoantibodies against amylase to normal levels in patients with autoimmune pancreatitis [53,58]. As a result, immune modulatory treatment for autoimmunity against amylase may potentially contribute to improved endocrine function in fulminant type 1 diabetes.…”

“…We have reported a high prevalence (more than 80%) of autoantibodies against amylase in patients with fulminant type 1 diabetes or autoimmune pancreatitis [53]. Autoimmune pancreatitis has recently been reported as a unique form of chronic pancreatitis [54].…”