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Autoantigens in type 1 diabetes mellitus

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References

  1. Castano L., Eisenbarth G.S. Type 1 diabetes: a chronic autoimmune disease of the human, mouse and rat. Ann. Rev. Immunol. 8: 647, 1990.

    Article  CAS  Google Scholar 

  2. Bork O., Cohen I.R. T-cell autoimmunity in type 1 diabetes mellitus. Curr. Opinion. Immunol. 5: 903, 1993.

    Article  Google Scholar 

  3. Eisenbarth G.S. Type I diabetes mellitus: a chronic autoimmune disease. N. Engl. J. Med. 314: 1360, 1986.

    Article  PubMed  CAS  Google Scholar 

  4. Nepom G.T. Immunogenetics and IDDM. Diabetes Rev. 1: 93, 1993.

    Google Scholar 

  5. Rotella C., Dotta F., Mannucci E., Di Mario U. New evidence on autoantigens in thyroid and islet autoimmunity: similarities and differences. Autoimmunity 12: 223, 1992.

    Article  PubMed  CAS  Google Scholar 

  6. Bottazzo G.F., Gorsuch A.N., Dean B.M., Cudworth A.G., Doniach D. Complement fixing islet cell antibodies in Type 1 diabetes: possible monitors of active beta cell damage. Lancet 1: 668, 1980.

    Article  PubMed  CAS  Google Scholar 

  7. Bleich D., Jackson R.A., Soeldner J.S., Eisenbarth G.S. Analysis of metabolic progression to Type I diabetes in islet cell antibody positive relatives of patients with Type I diabetes. Diabetes Care 13: 111, 1990.

    Article  PubMed  CAS  Google Scholar 

  8. Miller B.J., Appel M.C., O’Neill J.J., Wicker L. Both the Lyt2+ and L3T4+ T cell subsets are required for the transfer of diabetes in NOD mice. J. Immunol. 140: 52, 1988.

    PubMed  CAS  Google Scholar 

  9. Bottazzo G.F., Florin-Christensen A., Doniach D. Islet cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiency. Lancet ii: 1279, 1974.

    Article  Google Scholar 

  10. Palmer J.P., Asplin C.M., Clemons P., Lyen K., Tatpati O., Raghu P., Paquette T.L. Insulin autoantibodies in insulin-dependent diabetes before insulin treatment. Science 222: 1337, 1983.

    Article  PubMed  CAS  Google Scholar 

  11. Atkinson M.A., MacLaren N.K. Islet cell autoantigens in insulin-dependent diabetes J. Clin. Invest. 1608, 1992.

  12. Greenbaum C., Palmer J.P., Kuglin B., Kolb H., and Participating Laboratories. Insulin autoantibodies measured by radioimmunoassay methodology are more related to insulin-dependent diabetes mellitus than those measured by enzyme-linked immunosorbent assay: Results of the fourth international workshop on the standardization of insulin autoantibody measurement. J. Clin. Endocrinol. Metab. 74: 1040, 1992.

    PubMed  CAS  Google Scholar 

  13. Vardi P., Ziegler A.G., Matthews J.H., Dib S.A., Keller R.J., Ricker A.T., Wolsdorf J.L., Herskowitz R.D., Rabizadeh A., Eisenbarth G.S., Soeldner J.S. Concentration of insulin autoantibodies at onset of Type I diabetes: inverse log-linear correlation with age. Diabetes Care 11: 736, 1988.

    PubMed  CAS  Google Scholar 

  14. Pugliese A., Bugawan T., Moromisato R., Eisenbarth G.S. Two subsets of HLA-DQA1 alleles mark phenotypic variation in levels of insulin autoantibodies in first degree relatives at risk for insulin-dependent diabetes J. Clin. Invest. 1994 in press.

  15. Ziegler A.G., Ziegler R., Vardi P., Jackson R.A., Soeldner J.S., Eisenbarth G.S. Life table analysis of progression to diabetes of anti-insulin autoantibody-positive relatives of individuals with type 1 diabetes. Diabetes 38: 1320, 1989.

    Article  PubMed  CAS  Google Scholar 

  16. Castano L., Ziegler A., Ziegler R., Shoelson S., Eisenbarth G.S. Characterization of insulin autoantibodies in relatives of patients with insulin-dependent diabetes mellitus. Diabetes 42: 1202, 1993.

    Article  PubMed  CAS  Google Scholar 

  17. Keller R.J. Cellular immunity to human insulin in prediabetic individuals. J. Autoimmun. 3: 321, 1990.

    Article  PubMed  CAS  Google Scholar 

  18. Harrison L.C., De Aizpurua H., Loudovaris T., Campbell I.L., Cebon J.S., Tait B.D., Colman P.G. Reactivity to human islets and fetal pig proislets by peripheral blood mononuclear cells from subjects with preclinical and clinical insulin-dependent diabetes. Diabetes, 40: 1128, 1991.

    Article  PubMed  CAS  Google Scholar 

  19. Ziegler A.G., Vardi P., Ricker A.T., Hattori M., Soeldner J.S., Eisenbarth G.S. Radioassay determination of insulin autoantibodies in NOD mice. Diabetes, 38: 358, 1989.

    Article  PubMed  CAS  Google Scholar 

  20. Zhang Z.J., Davidsen L., Eisenbarth G.S., Weiner H.L., Weiner R.S. Suppression of diabetes in NOD mice by oral administration of porcine insulin. Proc. Natl. Acad. Sci. USA 88: 10252, 1991.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Gottsfredsen C.F., Buschard K., Frandsen E.K. Reduction of diabetes incidence of BB Wistar rats by early prophylactic insulin treatment of diabetes-prone animals. Diabetologia 28: 933, 1985.

    Article  Google Scholar 

  22. Atkinson M.A., MacLaren N.K., Luchetta R. Insulitis and diabetes in NOD mice reduced by prophylactic insulin therapy. Diabetes, 39: 933, 1990.

    Article  PubMed  CAS  Google Scholar 

  23. Baekkeskov S., Nielsen J.H., Marner B., Bilde T., Ludvigsson J., Lernmark A. Autoantibodies in newly diagnosed diabetic children immunoprecipitate specific human islet cell proteins Nature, 298: 167, 1982.

    Article  PubMed  CAS  Google Scholar 

  24. Baekkeskov S., Dyrberg T., Lernmark A. Autoantibodies to a 64kD islet cell protein precede the onset of spontaneous diabetes in the BB reat. Science, 224: 1348, 1984.

    Article  PubMed  CAS  Google Scholar 

  25. Atkinson M.A., MacLaren N.K. Autoantibodies in NOD mice immunoprecipitate 64,000 Mr islet antigen. Diabetes, 37: 1587, 1988.

    Article  PubMed  CAS  Google Scholar 

  26. Baekkeskov S., Landin M., Kristensen J.K., Srikanta S., Bruining G.J., Mandrup-Poulsen T., de Beaufort C., Soeldner J.S., Eisenbarth G.S., Lindgren F., Sundquist G., Lernmark A. Antibodies to a Mr 64,000 human islet cell antigen precede the clinical onset of insulin-dependent diabetes. J. Clin. Invest., 79: 926, 1987.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Baekkeskov S., Warnock G., Christie M., Rajotte R.V., Mose-Larsen P., Fey S. Revelation of specificity of 64K autoantibodies in IDDM serums by high resolution 2D gel electrophoresis. Unambiguous identification of 64K target antigen. Diabetes, 38: 1133, 1989.

    CAS  Google Scholar 

  28. Atkinson M.A., MacLaren N.K., Scharp D.W., Lacy P.E., Riley W.J. 64000 Mr autoantibodies as predictors of insulin-dependent diabetes. Lancet 335: 1357, 1990.

    Article  PubMed  CAS  Google Scholar 

  29. Baekkeskov S., Aanstoot H., Christgau S., Reetz A., Solimena M., Cascalho M., Folli F., Richter-Olesen H., De Camilli P. Identification of the 64K autoantigen in insulin dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 347: 151, 1990.

    Article  PubMed  CAS  Google Scholar 

  30. Solimena M., Folli F., Aparisi R., Pozza G., De Camilli P. Autoantibodies to GABAergic neurons and pancreatic beta cells in Stiff-man syndrome. N. Engl. J. Med. 322: 1555, 1990.

    Article  PubMed  CAS  Google Scholar 

  31. Erdo S.L., Wolff J.R. Gamma-aminobutyric acid outside the mammalian brain. J. Neurochem. 54: 363, 1990

    Article  PubMed  CAS  Google Scholar 

  32. Karlsen A.E., Hagopian W.A., Grubin C.E., Dube S., Disteche C.M., Adler D.A., Barmaier H., Methewes S., Grant F.J., Foster D., Lermark A. Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10. Proc. Natl. Acad. Sci. USA, 88: 8337, 1991.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  33. Bu D.F., Erlander M.G., Hitz B.C., Tillakaratne N.J.K., Kaufman D.L., Wagner-McPherson C.B., Evans G.A., Tobin A.J. Two human glutamate decarboxylases, GAD65 and GAD67, are each encoded by a single gene. Proc. Natl. Acad. Sci. USA, 89: 2115, 1992.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  34. Erlander M.G., Tillakaratne N.J.K., Feldblum S., Pate N., Tobin A.J. Two genes encode distinct glutamate decarboxylases. Neuron 7: 91, 1991.

    Article  PubMed  CAS  Google Scholar 

  35. Reetz A., Solimena M., Matteoli M., Folli F., Takei K., De Camilli P. GABA and pancreatic ß cells: colocalization of Glutamic Acid Decarboxylase (GAD) and GABA with synaptic like microvescicles suggests their role in GABA storage and secretion. EMBO J. 10: 1275, 1991.

    PubMed Central  PubMed  CAS  Google Scholar 

  36. Christgau S., Aanstoot H.J., Schierbeck H., Begley K., Tullin S., Hejnaes K., Beakkeskov S. Membrane anchoring of the autoantigen GAD65 to microvescicles in pancreatic ß cells by palmitoylation in the NH2 terminal domain. J. Cell Bid. 118: 309, 1992.

    Article  CAS  Google Scholar 

  37. Li L., Hagopian W.A., Brashear H.R., Daniels T., Lernmark A. Identification of autoantibody epitopes of Glutamic Acid Decarboxylase in Stiff man syndrome patients. J. Immunol. 152: 930, 1994.

    PubMed  CAS  Google Scholar 

  38. Harrison L.C., Honeyman M.C., DeAizpurua Inverse relation between humoral and cellular immunity to glutamic acid decarboxylase in subjects at risk of insulin-dependent diabetes. Lancet 341: 1365, 1993.

    Article  PubMed  CAS  Google Scholar 

  39. Kaufman D.L., Clare-Salzler M., Tian J., Forsthuber T., Ting G.S.P., Robinson P., Atkinson M.A., Sercarz E.E., Tobin A.J., Lehmann P.V. Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabete Nature 366: 69, 1993.

    Article  PubMed  CAS  Google Scholar 

  40. Tisch R., Yang X.D., Singer S.M., Liblau R.S., Fugger L., McDevitt H.O. Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice. Nature 366: 72, 1993.

    Article  PubMed  CAS  Google Scholar 

  41. Castano L., Russo E., Zhou L., Lipes M.A., Eisenbarth G.S. Identification and cloning of a granule autoantigen (carboxypeptidase H) associated with type 1 diabetes. J. Clin. Endocrinol. Metab. 73: 1197, 1991.

    Article  PubMed  CAS  Google Scholar 

  42. Powers A.C., Bowen S., West S. Carboxypeptidase H is an autoantigen of the ICA and is expressed on the cell surface of islet cells. Diabetes 40 (suppl.): 1a, 1991.

    Article  Google Scholar 

  43. Hakomori S.I. Glycosphingolipids in cellular interaction, differentiation and oncogenesis. Ann. Rev. Biochem., 50: 733, 1981.

    Article  PubMed  CAS  Google Scholar 

  44. Alejandro R., Shienvold F.L., Hayek S.A.V., Pierce M., Paul R., Mintz D.H. A ganglioside antigen on the rat pancreatic B cell surface identified by monoclonal antibody R2D6. J. Clin. Invest., 74: 25, 1984.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  45. Dotta F., Colman P.G., Nayak R.C., Lombardi D., Scharp D.W., Andreani D., Pontieri G.M., Di Mario U., Lenti L., Eisenbarth G.S. Ganglioside expression in human pancreatic islets. Diabetes, 38: 1478, 1989.

    Article  PubMed  CAS  Google Scholar 

  46. Dotta F., Tiberti C., Previti M., Anastasi E., Andreani D., Lenti L., Pontieri G.M., Gianani R., Appel M.C., Eisenbarth G.S., Di Mario U. Pancreatic ganglioside expression and cytolasmic islet cell antibody antigen in BB Diabetes-Prone, BB Diabetes-Resistant and Wistar Furth rats. Clin. Immunol. Immunopathol. 66: 143, 1993.

    Article  PubMed  CAS  Google Scholar 

  47. Dotta F., Peterson L.B., Previti M., Metzger J., Tiberti C., Anastasi E., Zoppitelli, Wicker L.S., Di Mario U. Pancreatic islet ganglioside expression in Non Obese Diabetic mice: comparison with C57BL/10 mice and changes after autoimmune B cell destruction. Endocrinology 130: 37, 1992.

    PubMed  CAS  Google Scholar 

  48. Colman P.G., Nayak R.C., Campbell I.L., Eisenbarth G.S. Binding of cytoplasmic islet cell antibodies is blocked by human pancreatic glycolipid extracts. Diabetes 37: 645, 1988.

    Article  PubMed  CAS  Google Scholar 

  49. Dotta F., Previti M., Tiberti C., Lenti L., Pugliese G., Di Mario U. Identification of the GM2-1 islet ganglioside: similarities with a major neuronal autoantigen. Diabetes, 41 (Suppl.): 365A, 1992

    Google Scholar 

  50. Fredman P., Vedeler C.A., Nyland H., Aarli J.A., Svennerholm L. Antibodies in sera from patients with inflammatory demyelinating poliradiculoneuropathy react with ganglioside LM1 and sulphatide of peripheral nerve myelin. J. Neurol. 238: 75, 1991.

    Article  PubMed  CAS  Google Scholar 

  51. Dotta F., Dionisi S., Gianani R., Lollobrigida L., Previti M., Lenti L., Eisenbarth G., Di Mario U. Expression of autoantibodies to the GM2-1 islet ganglioside precedes the onset of type 1 diabetes in high risk subjects. Diabetologia, 36 (Suppl.): 28A, 1993.

    Google Scholar 

  52. Pietropaolo M., Castano L., Babu S., Buelow R., Kuo Y.L.S., Martin S., Martin A., Powers A.C., Prochazka M., Naggert J., Leiter E.H., Eisenbarth G.S. Islet cell autoantigen 69kD (ICA69). Molecular cloning and characterization of a novel diabetes-associated autoantigen. J. Clin. Invest. 92: 359, 1993.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  53. Borch-Jonsen K., Joner G., Mandrup Poulsen T., Christy M., Kastrup K., Nerup J. Relationship between breast feeding and incidence rates of IDDM. Lancet, ii: 1084, 1984

    Google Scholar 

  54. Dahl-Jorgensen K., Joner G., Hanssen K.F. Relationship between cow’s milk consumption and incidence of IDDM in childhood. Diabetes Care, 14: 1081, 1991.

    Article  PubMed  CAS  Google Scholar 

  55. Glerum M.B., Robinson B.H., Martin J.M. Could bovine serum albumin be the initiating antigen ultimately responsible for the development of insulin-dependent diabetes mellitus? Diabetes Res. 10: 103, 1989.

    PubMed  CAS  Google Scholar 

  56. Karjalainen J., Martin J.M., Knip M. A bovine albumin peptide as a possible trigger of insulin-dependent diabetes mellitus. N. Engl. J.Med. 327: 302, 1992.

    Article  PubMed  CAS  Google Scholar 

  57. Atkinson M.A., Bowman M.A., Kuo-Jang K., MacLaren N.K. Lack of immune responsiveness to bovine serum albumin in insulin-dependent diabetes. N. Engl. J. Med. 329: 1853, 1993.

    Article  PubMed  CAS  Google Scholar 

  58. Elias D., Markovits D., Reshef T., van der Zee E., Cohen I.R. Induction and therapy of autoimmune diabetes in the non-obese diabetic mouse by a 65kDa heat shock protein. Proc. Natl. Acad. Sci. USA, 87: 1576, 1990.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  59. Atkinson M.A., MacLaren N.K., Scharp D.W. No evidence for HSP65 in insulin dependent diabetes. Lancet, 337: 263, 1990.

    Google Scholar 

  60. Gianani R., Pugliese A., Bonner-Weir S. Prognostically significant heterogeneity of cytoplasmic islet cell antibodies in relatives of patients with Type I Diabetes. Diabetes 41: 347, 1992.

    Article  PubMed  CAS  Google Scholar 

  61. Genovese S., Bonifacio E., McNally J.M., Dean B., Wagner R., Bosi E., Gale E.A.M., Bottazzo G.F. Distinct cytoplasmic islet cell antibodies with different risks for type I (insulin-dependent) diabetes mellitus. Diabetologia 35: 385,1992.

    Article  PubMed  CAS  Google Scholar 

  62. Atkinson M.A., Kaufman D.L., Campbell L., Tobin A.J., MacLaren N.K. Islet cell cytoplasmic autoantibody reactivity to glutamate decarboxylase in insulin-dependent diabetes. J. Clin. Invest. 91: 350, 1993

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  63. Christie M.R., Tun R.Y.M., Lo S., Cassidy D., Brown T.J., Hollands J., Shattock M., Bottazzo G.F., Leslie R.D.G. Antibodies to GAD and to tryptic fragments of islet64K antigen as distinct markers for development of IDDM: studies with identical twins. Diabetes 41: 782, 1992.

    Article  PubMed  CAS  Google Scholar 

  64. Christie M.R., Hollands J.A., Brown T.J., Michelsen B.K., Delovitch T.L. Detection of pancreatic islet 64,000 Mr autoantigens in insulin-dependent diabetes distinct from glutamate decarboxylase. J. Clin. Invest., 22: 240, 1993.

    Article  Google Scholar 

  65. Roep B.O., Ardern S.D., De Vries R.R.P., Hutton J.C. T-cell clones from a type 1 diabetes patient respond to insulin secretory granule proteins. Nature, 345: 632, 1990.

    Article  PubMed  CAS  Google Scholar 

  66. Roep B.O., Kallan A.A., Hazenbos W.L.W., Bruining G.J., Baileys E.M., Ardern S.D., Hutton J.C., De Vries R.R.P. T cell reactivity to 38kD insulin-secretory-granule protein in patients with recent onset type 1 diabetes. Lancet 337: 1439, 1991.

    Article  PubMed  CAS  Google Scholar 

  67. Karounos D.G., Wolinsky J.S., Thomas J.W. Monoclonal antibody to rubella virus capside protein recognizes a ß-cell antigen. J. Immunol. 150/3080, 1993.

    PubMed  CAS  Google Scholar 

  68. Gillard B., Thomas J.W., Nell L.J., Marcus D.M. Antibodies against ganglioside GT3 in the sera of patients with type 1 diabetes mellitus. J. Immunol. 142: 3826, 1989.

    PubMed  CAS  Google Scholar 

  69. Dotta F., Wicker L., Peterson L., Pressey M., Appel M.C., Eisenbarth G.S. Inheritance of anti-polar antibodies in the NOD mouse: evidence for a single recessive gene. Diabetes, 38 (Suppl.): 76a, 1989.

    Article  Google Scholar 

  70. Wicker L.S., Appel M.C., Dotta F., Pressey A., Miller B.J., DeLarato N.H., Fischer A., Boltz R.C., Peterson L.B. Autoimmune syndromes in NOD.B10-H-2b (NOD.H-2b) and (NOD × NOD.H-2b)F1 mice: the NOD MHC is dominant for insulitis and cyclophosphamide-induced diabetes. J. Exp. Med., 176: 67, 1992.

    Article  PubMed  CAS  Google Scholar 

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Dotta, F., Anastasi, E., Tiberti, C. et al. Autoantigens in type 1 diabetes mellitus. J Endocrinol Invest 17, 497–508 (1994). https://doi.org/10.1007/BF03347744

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