Circulating antibodies against an exocrine pancreatic enzyme in type 1 diabetes

In this article, we report the identification of a new autoantigen in type 1 diabetes originating from the exocrine pancreas. This antigen is a pancre atic enzyme termed bile salt-dependent Lipase (BSDL), me show that antibodi es present in the sera of newly diagnosed type 1 diabetic patients recogniz e BSDL and more specifically the COOH-terminal mucin-like region of the pro tein. Therefore, me engineered the COOH-tenninal peptide of BSDL and demons trated that autoreactivity was Linked to specific glycosylation sites by at least two glycosyltransferases: the Core 2 beta(1-6)N-acetylglucosaminyltr ansferase and the alpha(1-3) fucosyltransferase FUT7. We next examined the prevalence of circulating anti-BSDL antibodies in type 1 diabetic patients and found 73.5% positivity (25 sera among 34 patients tested) at onset, whe reas only 8.4% of normal individuals (7 of 83) mere positive. Within a coho rt of first-degree relatives of diabetic patients followed prospectively un til development of diabetes, 6 of 19 (31.6%) were also positive. Interestin gly, two prediabetic individuals were already positive for anti-BSDL antibo dies (Abs), while islet cell cytoplasmic Abs and antibodies to GAD65, IA-2, and insulin were not detected. Anti-BSDL autoantibodies were weakly or not detected in patients suffering from pancreatitis or pancreatic adenocarcin oma or in patients with Graves' disease. Although autoreactivity to BSDL in prediabetic and newly diagnosed diabetic patients might reflect cross-reac tivity, our results strongly suggest that in addition to pancreatic beta-ce lls, acinar cells may be also affected in type 1 diabetes.