Circulating antibodies against an exocrine pancreatic enzyme in type 1 diabetes
- PMID: 10580419
- DOI: 10.2337/diabetes.48.12.2316
Circulating antibodies against an exocrine pancreatic enzyme in type 1 diabetes
Abstract
In this article, we report the identification of a new autoantigen in type 1 diabetes originating from the exocrine pancreas. This antigen is a pancreatic enzyme termed bile salt-dependent lipase (BSDL). We show that antibodies present in the sera of newly diagnosed type 1 diabetic patients recognize BSDL and more specifically the COOH-terminal mucin-like region of the protein. Therefore, we engineered the COOH-terminal peptide of BSDL and demonstrated that autoreactivity was linked to specific glycosylation sites by at least two glycosyltransferases: the Core 2 beta(1-6)N-acetylglucosaminyltransferase 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, whereas only 8.4% of normal individuals (7 of 83) were positive. Within a cohort of first-degree relatives of diabetic patients followed prospectively until development of diabetes, 6 of 19 (31.6%) were also positive. Interestingly, two prediabetic individuals were already positive for anti-BSDL antibodies (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 adenocarcinoma or in patients with Graves' disease. Although autoreactivity to BSDL in prediabetic and newly diagnosed diabetic patients might reflect cross-reactivity, our results strongly suggest that in addition to pancreatic beta-cells, acinar cells may be also affected in type 1 diabetes.
Similar articles
-
The formation of the oncofetal J28 glycotope involves core-2 beta6-N-acetylglucosaminyltransferase and alpha3/4-fucosyltransferase activities.Glycobiology. 1999 Sep;9(9):935-46. doi: 10.1093/glycob/9.9.935. Glycobiology. 1999. PMID: 10460835
-
Autoantibodies to protein tyrosine phosphatase-like proteins in type I diabetes. Overlapping specificities to phogrin and ICA512/IA-2.Diabetes. 1996 Oct;45(10):1344-9. doi: 10.2337/diab.45.10.1344. Diabetes. 1996. PMID: 8826969
-
IA-2 (islet cell antigen 512) is the primary target of humoral autoimmunity against type 1 diabetes-associated tyrosine phosphatase autoantigens.J Immunol. 1998 Sep 1;161(5):2648-54. J Immunol. 1998. PMID: 9725268
-
Pancreatic adenocarcinoma, chronic pancreatitis, and MODY-8 diabetes: is bile salt-dependent lipase (or carboxyl ester lipase) at the crossroads of pancreatic pathologies?Oncotarget. 2017 Dec 22;9(15):12513-12533. doi: 10.18632/oncotarget.23619. eCollection 2018 Feb 23. Oncotarget. 2017. PMID: 29552330 Free PMC article. Review.
-
[Detection of subjects at risk of type 1 diabetes. GOFEDI. Groupe Ouest-France pour l'Etude du Diabète Insulino-dépendant].Rev Med Interne. 1993 Jan;14(1):25-31. doi: 10.1016/s0248-8663(05)82518-4. Rev Med Interne. 1993. PMID: 8362105 Review. French.
Cited by
-
Type 1 Diabetes: A Disorder of the Exocrine and Endocrine Pancreas.J Cell Immunol. 2023;5(4):120-126. doi: 10.33696/immunology.5.177. J Cell Immunol. 2023. PMID: 38390030 Free PMC article.
-
Unravelling Checkpoint Inhibitor Associated Autoimmune Diabetes: From Bench to Bedside.Front Endocrinol (Lausanne). 2021 Nov 5;12:764138. doi: 10.3389/fendo.2021.764138. eCollection 2021. Front Endocrinol (Lausanne). 2021. PMID: 34803927 Free PMC article. Review.
-
DeepGP: An Integrated Deep Learning Method for Endocrine Disease Gene Prediction Using Omics Data.Front Cell Dev Biol. 2021 Jul 6;9:700061. doi: 10.3389/fcell.2021.700061. eCollection 2021. Front Cell Dev Biol. 2021. PMID: 34295899 Free PMC article.
-
Impaired exocrine pancreatic function in different stages of type 1 diabetes.BMJ Open Diabetes Res Care. 2021 Feb;9(1):e001158. doi: 10.1136/bmjdrc-2019-001158. BMJ Open Diabetes Res Care. 2021. PMID: 33589430 Free PMC article.
-
Exocrine Pancreas Dysfunction in Type 1 Diabetes.Endocr Pract. 2020 Dec;26(12):1505-1513. doi: 10.4158/EP-2020-0295. Endocr Pract. 2020. PMID: 33471743 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical