Summary
A radiobinding assay for the detection of autoantibodies against islet amyloid polypeptide was developed, analytically validated, and -in parallel with a similar assay for the detection of autoantibodies against insulin — applied to sera from recent-onset Type 1 (insulin-dependent) diabetic patients and from age- and sex-matched control subjects. There was no difference in islet amyloid polypeptide autoantibody titres between patient groups and matched control subjects, nor within subject groups according to age. At onset of Type 1 diabetes, elevated islet amyloid polypeptide-autoantibody levels (> 97th percentile of control subjects) were only detected in 1 of 30 patients aged 0–19 years and in 2 of 35 patients aged 20–39 years. By contrast, insulin autoantibodies were frequently demonstrated, in particular at onset of diabetes under age 20 (0–19 years: 18 of 30 patients; 20–39 years: 10 of 35 patients; p < 0.01 vs matched control subjects). Islet amyloid polypeptide autoantibodies were not detectable in 3 insulinoma patients nor in 37 patients (aged 33–70 years) with Type 2 diabetes (vs 1 of 40 in matched control subjects). In positive serum, adsorption onto protein A-Sepharose removed islet amyloid polypeptide binding activity, hereby confirming its antibody nature. In conclusion, Type 1 diabetes is associated with an age-dependent autoantibody reaction against insulin but not against islet amyloid polypeptide. Conditions associated with amyloid deposition in islets (Type 2 diabetes, insulinoma and ageing) do not favour the formation of autoantibodies against islet amyloid polypeptide.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Drell DW, Notkins AL (1987) Multiple immunological abnormalities in patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30: 132–143
Wilkin TJ (1991) Autoantibodies as mechanisms, markers, and mediators of B-cell disease. Diabetes Metab Rev 7: 105–120
Maclaren NK (1988) How, when and why to predict IDDM. Diabetes 37: 1591–1594
Tarn AC, Thomas JM, Dean BM et al. (1988) Predicting insulin-dependent diabetes. Lancet I: 845–850
Bruining GJ, Molenaar JL, Grobbe DE et al. (1989) Ten year follow-up study of islet cell antibodies and childhood diabetes mellitus. Lancet I: 1100–1103
Bonifacio E, Bingley PJ, Shattock M et al. (1990) Quantification of islet cell antibodies and prediction of insulin-dependent diabetes. Lancet 335: 147–149
Palmer JP, Asplin CM, Clemons P et al. (1983) Insulin antibodies in insulin-dependent diabetics before insulin treatment. Science 222: 1337–1339
Baekkeskov S, Aanstoot H-J, Christgau S et al. (1990) Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 347: 151–156
Christie MR, Brown TJ, Cassidy D (1992) Binding of antibodies in sera from type 1 (insulin-dependent) diabetic patients to glutamate decarboxylase from rat tissues. Evidence for antigenic and non-antigenic forms of the enzyme. Diabetologia 35: 380–384
Kuglin B, Gries FR, Kolb H (1988) Evidence of IgG autoantibodies against human proinsulin in patients with IDDM before insulin treatment. Diabetes 37: 130–132
Karjalainen J, Knip M, Mutsonen A, Ilonen J, Åkerblom HK (1986) Relation between insulin antibody and complement-fixing islet cell antibody at clinical diagnosis of IDDM. Diabetes 35: 620–622
Ludvigsson J, Binder C, Mandrup-Poulsen T (1988) Insulin autoantibodies are associated with islet cell antibodies: their relation to insulin antibodies and B-cell function in diabetic children. Diabetologia 31: 647–651
Thivolet Ch, Beaufrère B, Bétuel H et al. (1988) Islet cell and insulin autoantibodies in subjects at high risk for development of type 1 (insulin-dependent) diabetes mellitus: the Lyon family study. Diabetologia 31: 741–746
Ziegler AG, Ziegler R, Vardi P et al. (1989) Life table analysis of progression to diabetes of anti-insulin autoantibody-positive relatives of individuals with type 1 diabetes. Diabetes 38: 1320–1325
Cooper GJS, Day AJ, Willis AC, Roberts AN, Raid KBM, Leighton B (1989) Amylin and the amylin genes: structure, function and relationship to islet amyloid and to diabetes mellitus. Biochim Biophys Acta 1014: 247–258
Nishi M, Sanke T, Nagamatsu S, Bell GI, Steiner DF (1990) Islet amyloid polypeptide. A new β-cell secretory product related to islet amyloid deposits. J Biol Chem 265: 4173–4176
Johnson KH, O'Brien TD, Westermark P (1991) Newly identified pancreatic protein islet amyloid polypeptide: what is its relationship to diabetes? Diabetes 40: 310–314
Sodoyez-Goffaux F, Koch M, Dozio N, Brandenburg D, Sodoyez JC (1988) Advantages and pitfalls of radioimmune and enzyme linked immunosorbent assays of insulin antibodies. Diabetologia 31: 694–702
Palmer JP, Wilkin TJ, Kurtz AB, Bonifacio E (1990) The third international workshop on the standardisation of insulin autoantibody measurement. Diabetologia 33: 60–61
Kuglin B, Kolb H, Greenbaum C, Maclaren NK, Lernmark Å, Palmer JP (1990) The fourth international workshop on the standardisation of insulin autoantibody measurement. Diabetologia 33: 638–639
Lévy-Marchal C, Bridel MP, Sodoyez-Goffaux F et al. (1991) Superiority of radiobinding assay over enzyme-linked immunosorbent assay for detection of insulin autoantibodies in newly diagnosed type 1 diabetic patients. Diabetes Care 14: 61–63
Greenbaum C, Palmer JP, Kuglin B, Kolb H and participating laboratories (1992) Insulin autoantibodies measured by R1A methodology are more related to IDDM than those measured by ELISA. J Clin Endocrinol Metab 74: 1040–1044
Dziarski R (1988) Autoimmunity: polyclonal activation or antigen induction? Immunol Today 9: 340–342
Tomer Y, Shoenfeld Y (1988) Ageing and autoantibodies. Auto-immunity 1: 141–149
Laureys M, Sion JP, Slabbynck H et al. (1991) Macrocreatine kinase type 1: a serum marker associated with disease. Clin Chem 37: 430–434
Decraene T, Vandewalle C, Pipeleers DG, Gorus FK and the Belgian Diabetes Registry (1992) Elevated IgM concentrations at onset of type 1 (insulin-dependent) diabetes: correlation with IgM binding to cells. Clin Chem 38: 1762–1769
National Diabetes Data Group (1979) Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28: 1039–1057
Tan WP (1990) Insulin autoantibodies in newly diagnosed insulin-dependent diabetic patients. M. Sc. thesis, Vrije Universiteit Brussel, Brussels
Srikanta S, Ricker AT, McCulloch DK, Soeldner JS, Eisenbarth GS, Palmer JP (1986) Autoimmunity to insulin, beta cell dysfunction and development of insulin-dependent diabetes mellitus. Diabetes 35: 139–142
Van Schravendijk CFH, Foriers A, Hooghe-Peters EL et al. (1985) Pancreatic hormone receptors on islet cells. Endocrinology 117: 841–848
Nakazato M, Asai J, Kangawa K, Matsukura S, Matsuo H (1989) Establishment of a radioimmunoassay for human islet amyloid polypeptide and its tissue content and plasma concentration. Biochem Biophys Res Commun 164: 394–399
Sodoyez JC, Koch M, Sodoyez-Goffaux F (1991) Anticorps anti-insuline: methodologie et implications cliniques. Diabète Métab 17: 255–269
Bottazzo GF, Florin-Christensen A, Doniach D (1974) Islet cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet II: 1279–1283
Bonifacio E, Boitard C, Gleichmann H et al. (1990) Assessment of precision, concordance, specificity, and sensitivity of islet cell antibody measurement in 41 assays. Diabetologia 33: 731–736
Karjalainen J, Knip M, Hyöty H et al. (1988) Relationship between serum insulin autoantibodies, islet cell antibodies and Coxsackie-B4 and mumps virus-specific antibodies at the clinical manifestation of type 1 (insulin-dependent) diabetes. Diabetologia 31: 146–152
Vardi P, Ziegler AG, Mathews JH et al. (1989) Concentration of insulin autoantibodies at onset of type 1 diabetes. Diabetes Care 11: 1320–1325
Castaño L, Russo E, Zhou L, Lipes MA, Eisenbarth GS (1991) Identification and cloning of a granule autoantigen (carboxypeptidase-H) associated with type 1 diabetes. J Clin Endocrinol Metab 73: 1197–1201
Clark A, Yon SM, de Koning EJP, Holman RK (1991) Autoantibodies to islet amyloid polypeptide in diabetes. Diabetic Med 8: 668–673
Sodoyez JC, Koch M, Lemaire I et al. (1991) Influence of affinity of antibodies upon their detection by liquid phase radiobinding assay and solid phase enzyme linked immunosorbent assay. Demonstration using monoclonal antibodies raised against rDNA human proinsulin. Diabetologia 34: 463–468
Holmberg D, Coutinho A (1985) Natural antibodies and autoimmunity. Immunol Today 6: 356–357
Theofilopoulos AN (1987) Autoimmunity. In: Stiter DP, Stobo JD, Wells JU (eds) Basic and clinical immunology. 6th edn. Appleton & Lange, Norwalk, pp 128–158
Tamer JA, Getzoff ED, Paterson Y, Olson AJ, Lerner RA (1985) The atomic mobility component of protein antigenicity. Ann Rev Immunol 3: 501–535
Barlow PJ, Edwards MS, Thornton JM (1986) Continuous and discontinuous protein antigenic determinants. Nature 322: 747–748
Westhof E, Altschuk D, Moras D et al. (1984) Correlation between segmental mobility and the location of antigenic determinants in protein. Nature 311: 123–126
Fineberg SE, Rathbun MJ, Hufferd S et al. (1988) Immunologic aspects of human proinsulin therapy. Diabetes 37: 276–280
Author information
Authors and Affiliations
Consortia
Rights and permissions
About this article
Cite this article
Gorus, F.K., Sodoyez, J.C., Pipeleers, D.G. et al. Detection of autoantibodies against islet amyloid polypeptide in human serum. Lack of association with Type 1 (insulin-dependent) diabetes mellitus, or with conditions favouring amyloid deposition in islets. Diabetologia 35, 1080–1086 (1992). https://doi.org/10.1007/BF02221685
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02221685