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01-11-2013 | For Debate

Is there evidence for post-translational modification of beta cell autoantigens in the aetiology and pathogenesis of type 1 diabetes?

Author: Åke Lernmark

Published in: Diabetologia | Issue 11/2013

Abstract

Størling and colleagues hypothesise in this issue (Diabetologia DOI:10.1007/s00125-013-3045-3) that post-translational modification (PTM) of autoantigens might create tissue-specific neo-epitopes that could trigger type 1 diabetes. Data on PTM of islet autoantigens are scarce and readers should not believe that the PTM hypothesis is supported by strong experimental evidence. The proposed genetic factors are many but their possible contribution is conjectural. There is a lack of a rational approach to test the PTM hypothesis at the different stages of type 1 diabetes. Research that carefully addresses each stage of the type 1 diabetes disease process is warranted to advance our understanding of autoimmune (type 1) diabetes.

Eisenbarth GS (1986) Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med 314:1360–1368PubMedCrossRef

Størling J, Overgaard AJ, Brorsson CA et al (2013) Do post-translational beta cell protein modifications trigger type 1 diabetes? Diabetologia doi:10.1007/s00125-013-3045-3

Concannon P, Rich SS, Nepom GT (2009) Genetics of type 1A diabetes. N Engl J Med 360:1646–1654PubMedCrossRef

Torn C, Mueller PW, Schlosser M, Bonifacio E, Bingley PJ (2008) Diabetes Antibody Standardization Program: evaluation of assays for autoantibodies to glutamic acid decarboxylase and islet antigen-2. Diabetologia 51:846–852PubMedCrossRef

Bonifacio E, Yu L, Williams AK et al (2010) Harmonization of glutamic acid decarboxylase and islet antigen-2 autoantibody assays for national institute of diabetes and digestive and kidney diseases consortia. J Clin Endocrinol Metab 95:3360–3367PubMedCrossRef

Lampasona V, Schlosser M, Mueller PW et al (2011) Diabetes antibody standardization program: first proficiency evaluation of assays for autoantibodies to zinc transporter 8. Clin Chem 57:1693–1702PubMedCrossRef

Palmer JP, Asplin CM, Clemons P et al (1983) Insulin antibodies in insulin-dependent diabetics before insulin treatment. Science 222:1337–1339PubMedCrossRef

Grubin CE, Daniels T, Toivola B et al (1994) A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM. Diabetologia 37:344–350PubMedCrossRef

Sosenko JM, Skyler JS, Palmer JP et al (2013) The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients. Diabetes Care 36:2615–2620

10.

Diabetes Prevention Trial—Type 1 Diabetes Study Group (2002) Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 346:1685–1691CrossRef

11.

Gale EA, Bingley PJ, Emmett CL, Collier T (2004) European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes. Lancet 363:925–931PubMedCrossRef

12.

James EA, Mallone R, Schloot NC et al (2011) Immunology of Diabetes Society T-Cell Workshop: HLA class II tetramer-directed epitope validation initiative. Diabetes Metab Res Rev 27:727–736PubMedCrossRef

13.

Brooks-Worrell B, Tree T, Mannering SI et al (2011) Comparison of cryopreservation methods on T-cell responses to islet and control antigens from type 1 diabetic patients and controls. Diabetes Metab Res Rev 27:737–745PubMedCrossRef

14.

Oikarinen S, Martiskainen M, Tauriainen S et al (2011) Enterovirus RNA in blood is linked to the development of type 1 diabetes. Diabetes 60:276–279PubMedCrossRef

15.

Masala S, Paccagnini D, Cossu D et al (2011) Antibodies recognizing Mycobacterium avium paratuberculosis epitopes cross-react with the beta-cell antigen ZnT8 in Sardinian type 1 diabetic patients. PLoS One 6:e26931PubMedCrossRef

16.

Stene LC, Oikarinen S, Hyoty H et al (2010) Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the Diabetes and Autoimmunity Study in the Young (DAISY). Diabetes 59:3174–3180PubMedCrossRef

17.

Baekkeskov S, Kanaani J (2009) Palmitoylation cycles and regulation of protein function (review). Mol Membr Biol 26:42–54PubMedCrossRef

18.

Graham J, Hagopian WA, Kockum I et al (2002) Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes. Diabetes 51:1346–1355PubMedCrossRef

19.

Delli AJ, Vaziri-Sani F, Lindblad B et al (2012) Zinc transporter 8 autoantibodies and their association with SLC30A8 and HLA-DQ genes differ between immigrant and Swedish patients with newly diagnosed type 1 diabetes in the Better Diabetes Diagnosis study. Diabetes 61:2556–2564PubMedCrossRef

20.

Ziegler AG, Rewers M, Simell O et al (2013) Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 309:2473–2479PubMedCrossRef

21.

Hagopian WA, Erlich H, Lernmark A et al (2011) The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. Pediatr Diabetes 12:733–743PubMedCrossRef

22.

Lee HS, Briese T, Winkler C et al (2013) Next-generation sequencing for viruses in children with rapid-onset type 1 diabetes. Diabetologia 56:1705–1711PubMedCrossRef

23.

Roep BO, Peakman M (2012) Antigen targets of type 1 diabetes autoimmunity. Cold Spring Harb Perspect Med 2:a007781PubMedCrossRef

Title: Is there evidence for post-translational modification of beta cell autoantigens in the aetiology and pathogenesis of type 1 diabetes?
Author: Åke Lernmark
Publication date: 01-11-2013
Publisher: Springer Berlin Heidelberg
Published in: Diabetologia / Issue 11/2013
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-013-3041-7

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