Autoimmune diagnostics in diabetes mellitus

Abstract

Type 1 diabetes results from a specific destruction of the insulin-producing β-cells of the pancreas. The disease is characterized by the appearance of specific autoantibodies against islet cell antigens. Autoantibodies to insulin, glutamic acid decarboxylase, tyrosine phosphatase IA-2 and cytoplasmic islet cell antibodies are useful markers for the differential diagnosis of type 1 diabetes when clinical and metabolic criteria alone do not allow definite classification. Autoimmune diagnostics is of particular importance in adults to discriminate between type 1 and type 2 diabetes and to assess the diagnosis of latent autoimmune diabetes in adults.

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  • 1.

    Kerner W, Fuchs C, Redaelli M, Boehm BO, Köbberling J, Scherbaum WA, et al. Definition, Klassifikation und Diagnostik des Diabetes mellitus. In: Evidenzbasierte Diabetes-Leitlinien DDG, 1st ed. Scherbaum WA, Lauterbach KW, Joost HG, editors. Munich: Deutsche Diabetes-Gesellschaft, 2001.

  • 2.

    Schranz DB, Lernmark Å. Immunology in diabetes: an update. Diabetes Metab Rev 1998; 14:3–29.

  • 3.

    Seissler J, Scherbaum WA. Are we ready to predict and prevent endocrine/organ-specific autoimmune diseases? Springer Semin Immunopathol 2002; 24:273–95.

  • 4.

    Liu E, Eisenbarth GS. Type 1A diabetes mellitus-associated autoimmunity. Endocrinol Metab Clin North Am 2002; 31:391–410.

  • 5.

    Baekkeskov S, Aanstoot HJ, Christgau S, Reetz A, Solimena M, Cascalho M, et al. Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 1990; 347:151–6.

  • 6.

    Lan MS, Goto Y, Notkins AL. Molecular cloning and identification of a receptor-type protein tyrosine phosphatase, IA-2, from human insulinoma. DNA and Cell Biol 1994; 5:505–14.

  • 7.

    Vardi P, Ziegler AG, Mathews JH, Dib S, Keller RJ, Ricker AT, et al. Concentration of insulin autoantibodies at onset of type I diabetes. Inverse log-linear correlation with age. Diabetes Care 1988; 11:736–9.

  • 8.

    Winter WE, Harris N, Schatz D. Type 1 diabetes islet autoantibody markers. Diabetes Technol Ther 2002; 4:817–39.

  • 9.

    Seissler J, Amann J, Mauch L, Haubruck H, Wolfahrt S, Bieg S, et al. Prevalence of autoantibodies to the 65- and 67-kDa isoforms of glutamate decarboxylase in insulin-dependent diabetes mellitus. J Clin Invest 1993; 92:1394–9.

  • 10.

    Verge CF, Howard NJ, Rowley MJ, MacKay IR, Zimmet P, Egan M, et al. Anti-glutamate decarboxylase and other antibodies at the onset of childhood IDDM: a population-based study. Diabetologia 1994; 37:1113–20.

  • 11.

    Seissler J, de Sonnaville JJ, Morgenthaler NG, Steinbrenner H, Glawe D, Khoo-Morgenthaler UY, et al. Immunological heterogeneity in type I diabetes: presence of distinct autoantibody patterns in patients with acute onset and slowly progressive disease. Diabetologia 1998; 41:891–7.

  • 12.

    Morgenthaler NG, Seissler J, Achenbach P, Glawe D, Payton M, Meinck HM, et al. Antibodies to the tyrosine phosphatase-like protein IA-2 are highly associated with IDDM, but not with autoimmune endocrine diseases or stiff man syndrome. Autoimmunity 1996; 25:202–12.

  • 13.

    Williams AJ, Bingley PJ, Bonifacio E, Palmer JP, Gale EA. A novel micro-assay for insulin autoantibodies. J Autoimmun 1997; 10:473–8.

  • 14.

    Greenbaum C, Palmer JP, Kuglin B, Kolb H. Insulin autoantibody measured by radioimmunoassay are more related to insulin-dependent diabetes mellitus than those measured by enzyme-linked immunosorbent assays: results of the fourth international workshop on the standardisation of insulin autoantibody measurement. J Clin Endocrinol Metab 1992; 74:1040–1.

  • 15.

    Scherbaum WA, Mirakian R, Pujol-Borrell R, Dean BM, Bottazzo GF. Immunochemistry in the study and diagnosis of organ-specific autoimmune disease. In: Polak JM, Van Noorden S, editors. Immunochemistry. Modern methods and applications. Bristol: Wright, 1986:456.

  • 16.

    Greenbaum CJ, Palmer JP, Nagataki S, Yamaguchi Y, Molenaar JL, Van Beers WA, et al. Improved specificity of ICA assays in the Fourth International Immunology of Diabetes serum exchange Workshop. Diabetes 1992; 41:570–4.

  • 17.

    Schloot NC, Roep BO. Islet antigen-specific T cell clones in autoimmune diabetes: from mice to men. Diabetes Metab Rev 1997; 13:127–38.

  • 18.

    Roep BO. Autoreactive T cells in endocrine/organ-specific autoimmunity: why has progress been so slow? Springer Semin Immunopathol 2002; 24:261–71.

  • 19.

    Wiest-Ladenburger U, Hartmann R, Hartmann U, Berling K, Boehm BO, Richter W. Combined analysis and single-step detection of GAD65 and IA2 autoantibodies in IDDM can replace the histochemical islet cell antibody test. Diabetes 1997; 46:565–71.

  • 20.

    Naik RG, Palmer JP. Latent autoimmune diabetes in adults (LADA). Rev Endocr Metab Disord 2003; 4:233–41.

  • 21.

    Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles WJ, MacKay IR. Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes in adults with a non-insulin-dependent onset of diabetes. Diabetes 1993; 42:359–62.

  • 22.

    Zimmet PZ, Tuomi T, MacKay IR, Rowley MJ, Knowles W, Cohen M, et al. Latent autoimmune diabetes mellitus in adults (LADA): the role of antibodies to glutamic acid decarboxylase in diagnosis and prediction of insulin dependency. Diabet Med 1994; 11:299–303.

  • 23.

    Turner R, Stratton I, Horton V, Manley S, Zimmet P, MacKay IR, et al. Autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group. Lancet 1997; 350:1288–93.

  • 24.

    Lohmann T, Kellner K, Verlohren HJ, Krug J, Steindorf J, Scherbaum WA, et al. Titer and combination of ICA and autoantibodies against glutamic acid decarboxylase discriminate two distinct types of latent autoimmune diabetes in adults. Diabetologia 2001; 44:1005–10.

  • 25.

    Seissler J, Morgenthaler NG, Achenbach P, Lampeter EF, Glawe D, Payton M, et al. Combined screening for autoantibodies to IA-2 and antibodies to glutamic acid decarboxylase in first degree relatives of patients with IDDM. Diabetologia 1996; 39:1351–6.

  • 26.

    Verge CF, Gianani R, Kawasaki E, Yu L, Pietropaolo M, Jackson RA, et al. Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes 1996; 45:926–33.

  • 27.

    Ziegler AG, Hummel M, Schenker M, Bonifacio E. Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB Study. Diabetes 1999; 48:460–8.

  • 28.

    Kimpimaki T, Kulmala P, Savola K, Vahasalo P, Reijonen H, Ilonen J, et al. Disease-associated autoantibodies as surrogate markers of type 1 diabetes in young children at increased genetic risk. Childhood Diabetes in Finland Study Group. J Clin Endocrinol Metab 2000; 85:1126–32.

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