Glutamic acid decarboxylase (GAD) in insulin-dependent diabetes mellitus

Diabetes, Nutrition and Metabolism - Clinical and Experimental

Volumn 9, Issue 4, 1996, Pages 167-182

  Sanjeevi, C B ^a,b   Falorni, A ^a,b   Robertson, J ^c   Lernmark, A ^a,d  

^a KAROLINSKA INSTITUTE   (Sweden)

^b UNIVERSITY OF PERUGIA   (Italy)

^c Synectics Biotechnology   (Sweden)

^d UNIVERSITY OF WASHINGTON   (United States)

Author keywords

Autoantibodies; Autoantigen; Autoimmunity; Diabetes mellitus; Prediction; Prevention; Radioimmunoassay

Indexed keywords

AUTOANTIBODY; AUTOANTIGEN; GLUTAMATE DECARBOXYLASE; MONOCLONAL ANTIBODY; VIRUS ANTIGEN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; AUTOIMMUNITY; ETIOLOGY; HLA SYSTEM; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; MOLECULAR MIMICRY; MOUSE; NONHUMAN; PANCREAS ISLET; PREDICTION; PRIORITY JOURNAL; RACE DIFFERENCE; RAT; T LYMPHOCYTE;

EID: 0029806942     PISSN: 03943402     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (174)

1. Falorni A., Kockum I., Sanjeevi C.B., Lernmark Å.: Pathogenesis of insulin-dependent diabetes mellitus. In: Kendall-Taylor P. (Ed) , Autoimmune endocrine disease. Baillière's Clinical Endocrinology & Metabolism vol 9, 1995, pp. 25-46.
2. Greenbaum C.J., Brooks-Worrell B.M., Palmer J.P., Lernmark Å.: Autoimmunity and prediction of insulin dependent diabetes mellitus. Diabetes Annual 8: 21-52, 1994.
3. Ellis T.M., Atkinson M.A.: The clinical significance of an autoimmune response against glutamic acid decarboxylase. Nature Med. 2: 148-153, 1996.
4. DIAMOND: Childhood Diabetes, Epidemics and Epidemiology: An approach for controlling diabetes. Am. J. Epidemiol. 135: 803-816, 1992.
5. LaPorte R.E., Tajima N., Åkerblom H.K., Berlin N., Brosseau J., Christy M., Drash A.L., Fishbein H., Green A., Hamman R., Harris M., King H., Laron Z., Neil A.: Geographic differences in the risk of insulin-dependent diabetes mellitus: the importance of registries. Diabetes Care 8: 101-107, 1985.
6. Karvonen M., Tuomiletho J., Libman I., LaPorte R., Group f.W.D.P.: A review of the recent epidemiological data on incidence of type 1 (insulin-dependent) diabetes mellitus worldwide. Diabetologia 36: 883-892, 1993.
7. Bodansky H.J., Staines A., Stephenson C., Haigh D., Cartwright R.: Evidence for an environmental effect in the aetiology of insulin dependent diabetes in a transmigratory population. Br. Med. J. 304: 1020-1022, 1992.
8. Dorman J.S., LaPorte R.E., Stone R.A., Trucco M.: World-wide differences in the incidence of type 1 diabetes are associated with aminoacid variation at position 57 of the DQ beta chain. Proc. Natl. Acad. Sci. USA 87: 7370-7374, 1990.
9. Gepts W.: Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 14: 619-633, 1965.
10. Foulis A.K., McGill M., Farquharson A.: Insulins in Type 1 (insulin-dependent) diabetes mellitus in man macrophages, lymphocytes, and interferon-λ containing cells. J. Pathol. 165: 97-103, 1991.
11. Lernmark Å., Kloppel G., Stenger D., Vathanaprida C., Fäit K., Landin-Olsson M., Baskin D.G., Palmer J.P., Gown A.M., Petersen J.S., Linsong L., Edenvall H., Mauseth R.S.: Heterogeneity of human islet pathology in newly diagnosed childhood insulin-dependent diabetes mellitus. Macrophage infiltrations and expression of HLA-DQ and glutamic acid decarboxylase. Virchows Arch. 425: 631-640, 1995.
12. Hänninen A., Jalkanen S., Salmi M., Toikkanen S., Nikolakaros G., Simell O.: Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus. J. Clin. Invest. 90: 1901-1910, 1992.
13. Lee K.U., Kim M.K., Amano K., Pak C.Y., Jaworski M.A., Mehta J.G., Yoon J.-W.: Preferential infiltration of macrophages during early stages of insulitis in diabetes-prone BB rats. Diabetes 37: 1053-1058, 1988.
14. Hanenberg H., Kolb-Bachofen V., Kantwerk-Funke G., Kolb H.: Macrophage infiltration precedes and is a prerequisite for lymphocytic insulitis in pancreatic islets of pre-diabetic BB rats. Diabetologia 32: 126-134, 1989.
15. Walker R., Bone A., Cooke A., Baird J.: Distinct macrophage subpopulations in pancreas of prediabetic BB/E rats. Diabetes 37: 1301-1304, 1988.
16. Lee K.U., Amano K., Yoon J.W.: Evidence for initial involvement of macrophage in development of insulitis in NOD mice. Diabetes 37: 989-991, 1988.
17. Bottazzo G.F., Florin-Christensen A., Doniach D.: Islet cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet II: 1279-1283, 1974.
18. MacCuish A.C., Barnes E.W., Irvine W.J., Duncan L.J.P.: Antibodies to pancreatic islet-cells in insulin-dependent diabetics with coexistent autoimmune disease. Lancet II: 1529-1531, 1974.
19. Bodansky H.J., Dean B.M., Bottazzo G.F., Grant P.J., McNally J., Hambling M.H., Wales J.K.: Islet-cell antibodies and insulin autoantibodies in association with common viral infections. Lancet II 1351-1353, 1986.
20. Landin-Olsson M., Karlsson A., Dahlquist G., Blom L., Lernmark Å., Sundkvist G.: Islet cell and other organ-specific autoantibodies in all children developing type 1 (insulin-independent) diabetes mellitus in Sweden during one year and in matched controls. Diabetologia 32: 387-395, 1989.
21. Baekkeskov S., Nielsen J.H., Marner B., Bilde T., Ludvigsson J., Lernmark Å.: Autoantibodies in newly diagnosed diabetic children immunoprecipitate human pancreatic islet cell proteins. Nature 298: 167-169, 1982.
22. Baekkeskov S., Landin-Olsson M., Kristensen J.K., Srikanta S., Bruining G.J., Mandrup-Poulsen T., de Beaufort C., Soeldner J.S., Eisenbarth G., Lindgren F., Sundkvist G., Lernmark Å.: Antibodies to a Mr 64,000 human islet cell antigen precede the clinical onset of insulin-dependent diabetes. J. Clin. Invest. 79: 926-934, 1987.
23. Hagopian W.A., Michelsen B., Karlsen A.E., Larsen F., Moody A., Grubin C.E., Rowe R., Petersen J., McEvoy R., Lernmark Å.: Autoantibodies in IDDM primarily recognize the 65,000-Mr rather than the 67,000-Mr isoform of glutamic acid decarboxylase. Diabetes 42:631-636, 1993.
24. Hagopian W.A., Karlsen A.E., Gottsater A., Landin-Olsson M., Grubin C.E., Sundkvist G., Petersen J.S., Boel E., Dyrberg T., Lernmark Å.: Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD-64) showed 64K autoantibody positivity at onset predicts diabetes type. J. Clin. Invest. 91: 368-374, 1993.
25. Grubln C.E., Daniels T., Toivola B., Landin-Olsson M., Hagopian W.A., Li L., Karlsen A.E., Boel E., Michelsen B., Lernmark Å.: A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM. Diabetologia 37: 344-350, 1994.
26. 3H recombinant human ligands. J. Immunol. Meth. 186: 89-99, 1995.
27. Palmer J.P., Asplin C.M., Clemons P., Lyen K., Tatpati O., Raghu P.K., Paguette T.L.: Insulin antibodies in insulin-dependent diabetics before insulin treatment. Science 222: 1337-1339, 1983.
28. Landin-Olsson M., Palmer J.P., Lernmark Å., Blom L., Sundkvist G., Nyström L., Dahlquist G.: Predictive value of islet cell and insulin autoantibodies for type 1 (insulin-dependent) diabetes mellitus in a population-based study of newly-diagnosed diabetic and matched control children. Diabetologia 35: 1068-1073, 1992.
29. Dotta F., Previti M., Lenti L., Dionisi S., Casetta B., D'Errne M., Eisenbarth G.S., Di Mario U.: GM2-I pancreatic islet ganglioside: identification and characterization of a novel islet-specific molecule. Diabetologia 38: 1117-1121, 1995.
30. Payton M.A., Hawkes C.J., Christie M.R.: Relationship of the 37,000- and 40,000-Mr tryptic fragments of islet antigens in insulin-dependent diabetes to the protein tyrosine phosphatase-like molecule IA-2 (ICA512). J. Clin. Invest. 96: 1506-1511, 1995.
31. Lan M.S., Lu J., Goto Y., Notkins A.L.: Molecular cloning and identification of a receptor-type protein tyrosine ptiosphatase, IA-2. from human insulinoma. DNA and Cell Biology 13:505-514, 1994.
32. Bonifacio E., Genovese S., Braghi S., Bazzigaluppi E., Lampasona V., Bingley P.J., Rogge L., Pastore M.R., Bognetti E., Bottazzo G.F., Gale E.A.M., Bosi E.: Islet autoantibody markers in IDDM: risk assessment strategies yielding high sensitivity. Diabetologia 38: 816-822, 1995.
33. Rabin D.U., Pleasic S.M., Shapiro J.A., Yoo-Warren H., Oles J., Hicks J.M., Goldstein D.E., Rae P.M.: Islet cell antigen 512 is a diabetes-specific islet autoantigen related to protein tyrosine phosphatases. J. Immunol. 152: 3183-3187, 1994.
34. Baekkeskov S., Dyrberg T., Lernmark Å.: Autoantibodies to a 64-kilodalton islet cell protein precede the onset of spontaneous diabetes in the BB rat. Science 224: 1348-1350, 1984.
35. Atkinson M.A., Maclaren N.K.: Autoantibodies in nonobese diabetic mice immunoprecipitate 64,000-Mr islet antigen. Diabetes 37: 1587-1590, 1988.
36. Atkinson M.A., Maclaren N.K., Scharp D.W., Lacy P.E., Riley W.J.: 64,000 Mr autoantibodies as predictors of insulin-dependent diabetes. Lancet 335: 1357-1360, 1990.
37. Bärmeier H., McCulloch D.K., Neifing J.L., Warnock G., Rajotte R.V., Palmer J.P., Lernmark Å.: Risk for developing type 1 (insulin-dependent) diabetes mellitus and the presence of islet 64K antibodies. Diabetologia 34: 727-733,1991.
38. Christie M.R., Pipeleers D.G., Lernmark Å., Baekkeskov S.: Cellular and subcellular localization of an Mr 64.000 protein autoantigen in insulin-dependent diabetes. J. Biol. Chem. 265: 376-381, 1990.
39. Solimena M., Folli F., Denis-Donini S., Comi G.C., Pozza G., De Camilli P., Vicari A.: Autoantibodies directed against glutamic acid decarboxylase (GAD) in the cerebrospinal fluid and serum of a patient with Stiff-Man syndrome, epilepsy and type I diabetes mellitus. N. Engl. J. Med. 318: 1012-1020, 1988.
40. Solimena M., Folli F., Aparisi R., Pozza G., De Camilli P.: Autoantibodies to GABA-ergic neurons and pancreatic beta cells in stiff-man syndrome. N. Engl. J. Med. 322: 1555-1560, 1990.
41. Baekkeskov S., Aanstoot H.J., 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: 151-156, 1990.
42. Erdo S.L., Wolff J.R.: Gamma-aminobutyric acid outside the mammalian brain. J. Neurochem. 54: 363-372, 1990.
43. Erlander M.G., Tobin A.J.: The structural and functional heterogeneity of glutamic acid decarboxylase: a review. Neurochem. Res. 16: 215-226, 1991.
44. Okada Y., Taniguchi H., Shimada C.: High concentration of GABA and high glutamate decarboxylase activity in rat pancreatic islets and human insulinoma. Science 194: 620-622, 1976.
45. Okada Y.: Localization and function of GABA in the pancreatic islets. In: Erdö S.L., Bowery N.G. (Eds), GABAergic mechanisms in The mammalian periphery. New York, Raven Press. 1986, pp. 223-240.
46. Michalik M., Nelson J., Erecinska M.: GABA production in rat islets of Langerhans. Diabetes 42: 1506-1513, 1993.
47. Vincent ST., Hökfelt T., Wu J.-Y., Eide R.P., Morgan L.M., Kimmel J.R.: Immunohistochemical studies of the GABA system in the pancreas. Neuroendocrinology 36: 197-204, 1983.
48. Gilon P., Bertrand G., Loubatieres-Mariani M.M., Remade C., Henquin J.C.: The influence of γ-aminobutyric acid on hormone release by the mouse and rat endocrine pancreas. Endocrinology 129: 2521-2529, 1991.
49. Karlsen A.E., Hagopian W.A., Grabin C.E., Dube S., Disteche C.M., Adler D.A., Barmeier H., Mathewes S., Grant F.J., Foster D., Lernmark Å.: Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10. Proc. Natl. Acad. Sci. USA 88: 8337-8341, 1991.
50. Michelsen B.K., Petersen J.S., Boel E., Møldrup A., Dyrberg T., Madsen O.D.: Cloning, characterization, and autoimmune recognition of rat islet glutamic acid decarboxylase in insulin-dependent diabetes mellitus. Proc. Nail. Acad. Sci. USA 88: 8754-8758, 1991.
51. Bu D.-F., Erlander M.G., Hitz B.C., Tillakaratne N.J.K., Kaufman D.L., Wanger-McPherson C.B., Evans G.A., Tobin A.J.: Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD. are each encoded by a single gene. Proc. Natl. Acad. Sci. USA 89: 2115-2119, 1992.
52. Bu D.F., Tobin A.J.: The exon-intron organization of the genes (GAD 1 and GAD2) encoding two human glutamate decarboxylases (GAD67 and GAD65) suggests that they derive from a common ancestral GAD. Genomics 11: 222-228, 1994.
53. Martin D.L., Rimvall K.: The regulation of GABA synthesis in the brain. J. Neurochem. 60: 395-407, 1993.
54. Martin D.L.: Short-term control of GABA synthesis in brain. Prog. Biophys. Molec. Biol. 60: 17-28, 1993.
55. Erlander M.G., Tillakaratne N.J.K., Feldblum S., Patel N., Tobin A J.: Two genes encode distinct glutamate decarboxylase. Neuron 7: 91-100, 1991.
56. Shi Y., Veit B., Baekkeskov S.: Amino acid residues 24-31 but not palmitoylation of cysteines 30 and 45 are required for membrane anchoring of glutamic acid decarboxylase, GAD65. J. Cell Biol. 124: 927-934, 1994.
57. Solimena M., Aggujaro D., Muntzel C., Dirkx R., Butler M., De Camilli P., Hayday A.: Association of GAD-65, but not of GAD-67, with the Golgi complex of transfected Chinese hamster ovary cells mediated by the N-terminal region. Proc. Natl. Acad. Sci. USA 90: 3073-3077, 1993.
58. Solimena M., Dirkx R., Jr., Radzynski M., Mudigl O., De Camilli P.: A signal located within amino acids 1-27 of GAD65 is required for its targeting to the Golgi complex region. J. Cell Biol. 126: 331-341, 1994.
59. 2-terminal region of the 65-kDa isoform of glutamic acid decarboxylase J. Biol. Chem. 270: 2241-2246, 1995.
60. Petersen J.B., Russel S., Marshall M.O., Kofod H., Buschard K., Cambon N., Karlsen A.E., Boel E., Hagopian W.A., Hejnæ K.R., Moody A., Dyrberg T., Lernmark Å., Madsen O.D., Michelsen B.K.: Differential expression of glutamic acid decarboxylase in rat and human islets. Diabetes 42: 484-495, 1993.
61. Cram D.S., Faulkner-Jones, B., Kun J., Harrison L.C.: Glutamic acid decarboxylase-67 (GAD67): Expression relative to GAD65 in human islets and mapping of autoantibody epitopes. Endocrinology 136: 1111-1119, 1995.
62. Mally M.I., Cirulli V., Otonkoski T., Soto G., Hayek A.: Ontogeny and tissue distribution of human GAD expression. Diaberes 45: 496-501, 1996.
63. Li L., Jiang J., Hagopian W. A., Karlsen A.E., Skelly M., Baskin D.G., Lernmark Å.: Differential detection of rat islet and brain glutamic acid decarboxylase (GAD) isoforms with sequence-specific peptide antibodies. J. Histochein. Cytochem. 43: 53-59, 1995.
64. Kaufman DJ., Erlander M.G., Clare-Salzler M., Atkinson M.A., Maclaren N.K., Tobin A.J.: Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus. J. Clin. Invest. 89: 283-292, 1992.
65. Karlsen A.E., Hagopian W.A., Petersen J.S., Boel E., Dyrberg T., Grubin C.E., Michelsen B.K., Madsen O.D., Lernmark Å.: Recombinant glutamic acid decarboxylase representing a single isoform expressed in human islets detects ID DM associated 64K autoantibodies. Diabetes 41: 1355-1359, 1992.
66. Björk E., Kämpe O., Karlsson F.A., Pipeleers D.G., Andersson A., Hellerström C., Eizink D.L.: Glucose regulation of the autoantigen GAD65 in human pancreatic islets. J. Clin. Endocrinol. Metab. 75: 1574-1576, 1992.
67. Velloso L.A., Björk E., Ballagi A.E., Funa K., Anderson A., Kämpe O., Karlsson F.A., Eizirik D.L.: Regulation of GAD expression in islets of Langerhans occurs both at the mRNA and protein level. Mol. Cell. Endocrinol. 101: 31-37, 1994.
68. Velloso L.A., Kämpe O., Hallberg A., Christmanson L., Betsholtz C., Karlsson F.A.: Demonstration of GAD-65 as the main immunogenic isoform of glutamate decarboxylase in type 1 diabetes and determination of autoantibodies using a radioligand produced by eukaryotic expression. J. Clin. Invest. 91: 2084-2090, 1993.
69. Seissler J., Amann J , Mauch L., Haubruck H., Wolfahrt S., Bieg S., Richter W., Holl R., Heinze E., Northemann W., Scherbaum W.A.: Prevalence of autoantibodies to the 65- and 67-kD isoforms of glutamate decarboxylase in insulin-dependent diabetes mellitus. J. Clin. Invest. 92: 1394-1399, 1993.
70. Petersen J.S., Hejnaes K.R., Moody A., Karlsen A. E., Marshall M.O., Hoier-Madsen M., Boel E., Michelsen B K., Dyrberg T.: Detection of GAD65 antibodies in diabetes and other autoimmune diseases using a simple radioligand assay. Diabetes 43: 459-465, 1994.
71. Vandewalle C.L., Falorni A., Svanholm S., Lernmark Å., Pipeleers D.G., Gorus F.K., Registry T.B.D.: High diagnostic sensitivity of glutamate decarboxylase autoantibodies in IDDM with clinical onset between age 20 and 40 years. J. Clin. Endocrinol. Metab. 80: 846-850, 1995.
72. Falorni A., Ackefors M., Carlberg C., Daniels T., Persson B., Robertson J., Lernmark Å.: Diagnostic sensitivity of immunodominant epitopes of glutamic acid decarboxylase (GAD65) autoantibodies in childhood IDDM. Diabetoiogia 39: 1091-1098, 1996.
73. Falorni A., Grubin C.E., Takei I., Shimada A., Kasuga A., Maruyama T., Ozawa Y., Kasatani T., Saruta T., Li L., Lernmark Å.: Radioimmunoassay detects the frequent occurrence of autoantibodies to the Mr 65,000 isoform of glutamic acid decarboxylase in Japanese insulin-dependent diabetes. Autoimmunity 19: 113-125, 1994.
74. Schmidli R.S., Colman P.G., Bonifacio E., Bottazzo G.F., Harrison L.C.: High level of concordance between assays for glutamic acid decarboxylase antibodies. The First International Glutamic Acid Decarboxylase Antibody Workshop. Diabetes 43: 1005-1009, 1994.
75. Schmidli R.S., Colman P.G., Bonifacio E.: Disease sensitivity and specificity of 52 assays for glutamic acid decarboxylase antibodies. The Second International GADAb Workshop. Diabetes 44: 636-640, 1995.
76. DeAizpurua H.J., Wilson Y.M., Harrison L.C.: Glutamic acid decarboxylase autoantibodies in preclinical insulin-dependent diabetes. Proc. Natl. Acad. Sci. USA 89: 9841-9845, 1992.
77. DeAizpurua H.J., Harrison L.C., Cram D.S.: An ELISA for antibodies to recombinant glutamic acid decarboxylase in IDDM. Diabetes 41: 1182-1187, 1992.
78. Rowley M.J., Mackay J.R., Chen Q.-Y., Knowles W.J., Zimmet P.Z.: Antibodies to glutamic acid decarboxylase discriminate major types of diabetes mellitus. Diabetes 41:548-551, 1992.
79. Christie M.R., Tun R.Y.M., Lo S.S.S., Cassidy D., Brown T.J.. Hollands J., Shattock M., Bottazzo G.F., Leslie R.D.G.: Antibodies to GAD and tryptic fragments of islet 64K antigen as distinct markers for development of IDDM. Diabetes 41: 782-787, 1992.
80. Tuomi T., Groop L.C., Zimmet P.Z., Rowley M.J., Knowles W., Mackay I.R.: Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease. Diabetes 42: 359-362, 1993.
81. Pfützner A., Seydlitz F., Ambrosch A., Forst T., Kann F.P., Schmitz H., Beyer J., Lichtwald K.: Serological study for the occurrence of antibodies to human glutamic acid decarboxylase in patients with Type 1 diabetes mellitus. Diab. Nutr. Metab. 7: 3-9, 1994.
82. Lühder F., Woltanski K.-P., Mauch L., Haubruck H., Kohnert K.-D., Rjasanowski I., Michaelis D., Ziegler M.: Detection of autoantibodies to the 65KDa isotbrm of glutamate decarboxylase by radioimmunoassay. Eur. J. Endocrinol. 130: 575-580, 1994.
83. Thivolet C., Tappaz M., Durand A., Petersen J., Stefanutti A., Chatelain P., Viaiettes B., Scherbaum W., Orgiazzi J.: Glutamic acid decarboxylase (GAD) autoantibodies are additional predictive markers of type 1 (insulin-dependent) diabetes mellitus in high risk individuals. Diabetologia 35: 570-576, 1992.
84. Tuomi T., Rowley M.J., Knowles W.J., Chen Q.-Y., McAnally Y., Zimmet P.Z . Mackay I.R.: Autoantigenic properties of native and denatured glutamic acid decarboxylase: Evidence for a conformational epitope. Clin. Immunol. Immunopathol. 71: 53-59, 1994.
85. Baekkeskov S., Warnock G., Christie M., Rajotte R.V., Larsen P.M., Fey S.: Revelation of specificity of 64K autoantibodies in IDDM serums by high-resolution 2-D gel electrophoresis. Diabetes 38: 1133-1141, 1990.
86. Grubin C., Daniels T., Karlsen A.E., Boel E., Hagopian W.A., Lernmark Å.: The cDNA-directed. in vitro-synthesized nascent peptide of glutamic acid decarboxylase (GAD2) is the autoantigen in insulin-dependent diabetes. Clin. Res. 40: 299A, 1992.
87. Falorni A., Nikosjkov A., Laureti S., Grenbäck E., Hulting A.-L., Casucci G., Santeusanio F., Brunetti P., Luthman H., Lernmark Å.: High diagnostic accuracy for idiopathic Addison's disease with a sensitive radiobinding assay for autoantibodies against recombinant human 21-hydroxylase. J. Clin. Endocrinol. Metab. 80: 2752-2755. 1995.
88. Gianani R., Rabin D.U., Verge C.F., Yu L., Babu S.R., Pietropaolo M., Eisenbanh G.E.: ICA512 autoantibody radioassay. Diabetes 44: 1340-1344, 1995.
89. WHO Study Group Diabetes mellitus. WHO Technical Report Series. 1985: 727.
90. Irvine W.J., Sawers J.S.A., Feek C.M., Prescott R.J., Duncanc J.P.: The value of islet cell antibody in predicting secondary failure of oral hypoglycemic agent therapy in diabetes mellitus. J. Clin. Immunol. 2: 23-26, 1979.
91. Groop L.C., Bottazzo G.F., Doniac D.: Islet cell antibodies identify latent type 1 diabetes in patients aged 35-75 years at diagnosis. Diabetes 35: 237-241, 1986.
92. Landin-Olsson M., Nilsson K.O., Lernmark Å., Sundkvist G.: Islet cell antibodies and fasting C-peptide predict insulin requirement at diagnosis of diabetes mellitus. Diabewlogia 33: 561-568, 1990.
93. Kasuga A., Maruyama T., Ozawa Y., Takei L., Falorni A., Lernmark Å., Saruta T.: Antibody to the Mr 65,000 isoform of glutamic acid decarboxylase are detected in noninsulin-dependent diabetes in Japanese. J. Autoimmun. 9: 105-111, 1996.
94. Kobayashi T., Sugimoto T., Itoh T., Kosaka K., Tanaka T., Suwa S., Sato K., Tsuji K.: The prevalence of islet cell antibodies in Japanese insulin-dependent and non-insulin-dependent diabetic patients studied by indirect immunofluorescence and by a new method. Diabetes 35: 335-340, 1986.
95. Kobayashi T., Itoh T., Kasaka K., Sato K., Tsuji K.: Time course of islet cell antibodies and β-cell function in non-insulin-dependent stage of Type 1 diabetes. Diabetes 36: 510-517.1987.
96. Kobayashi T., Tamemoto K., Nakanishi K., Kato N., Okubo M., Kajio H., Sugimoto T., Murase T., Kosaka K.: Immunogenetic and clinical characterization of slowly progressive IDDM. Diabetes Care 16: 780-788, 1993.
97. Zimmet P.Z., Tuomi T., Mackay I.R., Rowley M.J., Knowles W., Cohen M., Lang D.A.: Latent autoimmune diabetes mellitus in adults (LADA): The role of antibodies to glutamic acid decarboxylase in diagnosis and prediction of insulin dependency. Diabetic Med. 11: 299-303, 1994.
98. Landin-Olsson M., Karlsson F.A., Lernmark Å , Sundkvist G., Islet cell and thyrogastric antibodies in 633 consecutive 15-34 years old patients in the Diabetes Incidence Study in Sweden (DISS). Diabetes 41: 1022-1027, 1992.
99. Tuomilehto J., Zimmet P., Mackay I.R., Koskela P., Vidgren G., Tolvanen L., Tuomilehto-Wolf E., Kohtaraaki K., Stengård J., Rowley M.J.: Antibodies to glutamic acid decarboxylase as predictors of insulin-dependent diabetes mellitus before clinical onset of disease. Lancet 343: 1383-1385, 1994.
100. Ackefors M., Ivarsson S.A., Carlsson A., Ekberg G., Falorni A., Kockum I., Landin-Olsson M., Lernmark Å., Lindberg B., Sundkvist G., Svanberg L.: GAD65 autoantibodies and ICA during non-diabetic pregnancy precede IDDM but does not increase risk in offspring. Diabetohgia 38 (Suppl. 1): A70, 1995. (Abstract).
101. Dahlquist G., Ivarsson S., Lindberg B., Forsgren M.: Maternal enteroviral infection during pregnancy as a risk factor for childhood IDDM. Diabetes 44: 408-413, 1995.
102. Hyöty H., Hiltunen M., Knip M., Laakkonen M., Vahasalo P., Karjalainen J., Koskela P., Roivainen M., Leinikki P., Hovi T.: A prospective study of the role of coxsackie B and other enterovirus infections in the pathogenesis of IDDM. Childhood Diabetes in Finland (DiMe) Study. Diabetes 44: 652-657, 1995.
103. Serjeantson S.W., Kohonen-Corish M.R.J., Rowley M. J., Mackay I.R., Knowles W., Zimmer P.: Antibodies to glutamic acid decarboxylase are associated with HLA-DR genotypes in both Australians and Asians with Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 35: 996-1001, 1992.
104. Kawasaki E., Takino H., Yano M., Uotani S., Matsumoto K., Takao Y., Yamaguchi Y., Akazawa S., Nagataki S.: Autoantibodies to glutamic acid decarboxylase in patients with IDDM and autoimmune thyroid disease. Diabetes 43: 80-86, 1994.
105. Kasuga A., Falorni A., Maruyama T., Ozawa Y., Grubin C.E., Matsubara K., Takei I., Saruta T., Scheynius A., Lernmark Å.: HLA class II is associated with the frequency of glutamic acid decarboxylase Mr 65 000 autoantibodies in Japanese patients with insulin-dependent diabetes mellitus. Acta Diabetologica 33: 108-113, 1996.
106. Tuomi T., Zimmet P., Rowley M.J., Min H.K., Vichayanrat A., Lee H.K., Rhee B.D., Vannasaeng S., Humphrey A.R.G., Mackay I.R.: Differing frequency of autoantibodies to glutamic acid decarboxylase among Koreans, Thais, and Australians with diabetes mellitus. Clin. 1mmunol Immunopathol. 74: 202-206, 1995.
107. Zimmet P.Z., Rowley M.J., Mackay I.R., Knowles W.J., Chen Q.-Y., Chapman L.H., Serjeantson S.W.: The ethnic distribution of antibodies to glutamic acid decarboxylase: Presence and levels in insulin-dependent diabetes mellitus in Europid and Asian subjects. Lancet 340: 1-7, 1993.
108. Bosi E., Becker F., Bonifacio E., Wagner R., Collins P., Gale E.A.M., Bottazzo G.F.: Progression to Type 1 diabetes in autoimmune endocrine patients with islet cell antibodies. Diabetes 40: 977-984, 1991.
109. Wagner R., Genovese S., Bosi E., Becker F., Bingley P.J., Bonifacio E., Miles K.A., Christie M.R., Bottazzo G.F., Gale E.A.: Slow metabolic deterioration towards diabetes in islet cell antibody positive patients with autoimmune polyendocrine disease. Diabetologia 37: 365-371, 1994.
110. Solimena M., De Camilli P.: Autoimmunity to glutamic acid decarboxylase (GAD) in Stiff Man syndrome and insulin-dependent diabetes mellitus. Trends Neurosci. 14: 452-457, 1991.
111. Velloso L.A., Winqvist O., Gustafsson J., Kämpe O., Karlsson F.A.: Autoantibodies against a novel 51 kDa islet antigen and glutamate decarboxylase isoforms in autoimmune polyendocrine syndrome type I. Diabetologia 37: 61-69, 1994.
112. Tuomi T., Björses P., Falorni A., Partanen J., Perheentupa J., Lernmark Å., Miettinen A.: Antibodies to glutamic acid decarboxylase and insulin-dependent diabetes in patients with APS I (autoimmune polyendocrine syndrome Type I). J. Clin. Endocrinol. Metab. 81: 1488-1494, 1996.
113. Hallengren B., Falomi A., Landin-Olsson M., Lernmark Å., Papadopoulos K.I., Sundkvist G.: Islet cell and glutamic acid decarboxylase antibodies in hyperthyroid patients: at diagnosis and following treatment. J. Int. Med. 239: 63-68, 1996.
114. Daw K., Powers A.C.: Two distinct glutamic acid decarboxylase auto-antibody specificities in IDDM target different epitopes. Diabetes 44: 216-220, 1995.
115. 2-terminal epitope in the autoantigen GAD65, distinguish Stiff-Man Syndrome from insulin-dependent diabetes mellitus. J. Exp. Med. 180: 595-606.1994.
116. Nemni R., Braghi S., Natali-Sore M.G., Lampasona V., Bonifacio E., Comi G., Canal N.: Autoantibodies to glutamic acid decarboxylase in palatal myoclonus and epilepsy. Ann. Neurol. 36: 665-667, 1994.
117. Bonifacio E., Bingley P.J., Shattock M., Dean B.M., Dunger D., Gale E.A.M., Bottazzo G.F.: Quantification of islet cell antibodies and prediction of insulin dependent diabetes. Lancet 335: 147-149, 1990.
118. Bingley P.J., Bonifacio E., Shattock M., Gillmor H.A., Sawtell P.A., Dunger D.B., Scott R.D.M., Bottazzo G.F., Gale E.A.M.: Can islet cell antibodies predict IDDM in the general population? Diabetes Care 16: 45-50, 1993.
119. Bingley P.J., Christie M.R., Bonifacio E., Bonifanti R., Shattock M., Fonte M.T., Bottazzo G.F., Gale E.A.: Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives. Diabetes 43: 1304-1310, 1994.
120. Hagopian W.A., Sanjeevi C.B., Kockum I., Landin-Olsson M., Karlsen A.E., Sundkvist G., Dahlquist G., Palmer J., Lernmark Å.: Glutamate decarboxylase- insulin- and islet cell-antibodies and HLA typing to detect diabetes in a general population-based study of Swedish children. J. Clin. Invest. 95: 1505-1511, 1995.
121. Bingley P.J., Bonifacio E., Gale E.A.M.: Can we really predict IDDM? Diabetes 42: 213-220, 1993.
122. Genovese S., Bingley P.J., Bonifacio E., Christie M.R., Shattock M., Bonfanti R., Foxon R., Gale E.A.M.. Bottazzo G.F.: Combined analysis of IDDM-related autoantibodies in healthy school children. Lancet 344: 756, 1994.
123. Warram J.H., Krolewski A.S., Gottlieb M.S., Kahn C.R.: Differences in risk of insulin-dependent diabetes in offspring of diabetic mothers and diabetic fathers. N. Engl. J. Med. 311: 149-152, 1984.
124. Yu L., Chase H.P., Falorni A., Rewers M., Lernmark Å., Eisenbarth G.S.: Sexual dimorphism in transmission to offspring of expression of islet autoantibodies. Diabetologia 38: 1353-1357, 1995.
125. Björk E., Velloso L.A., Kämpe O., Karlsson F.A.: GAD autoantibodies in IDDM, Stiff-Man Syndrome, and autoimmune polyendocrine syndrome type I recognize different epitopes. Diabetes 43: 161-165, 1994.
126. Butler M.H., Solimena M., Dirkx J., R., Hayday A., De Camilla P.: Identification of a dominant epitope of glutamic acid decarboxylase (GAD-65) recognized by autoantibodies in Stiff-Man Syndrome. J. Exp. Med. 178: 2097-2106, 1993.
127. Li L., Hagopian W.A., Brashear H.R., Daniels T., Lernmark Å.: Identification of autoantibody epitopes of glutamic acid decarboxylase in Stiff-Man Syndrome patients. J. Immunol. 152: 930-934, 1994.
128. Daw K., Ujihara N., M. A., Powers A.: Glutamic acid decarboxylase autoantibodies in Stiff-Man Syndrome and insulin-dependent diabetes mellitus exhibit similarities and differences in epitope recognition. J. Immunol. 156: 818-815, 1996.
129. Richter W., Endl J., Eiermann T.H., Brandt M., Kientsch-Engel R., Thivolet C., Jungfer H., Scherbaum W.A.: Human monoclonal islet cell antibodies from a patient with insulin-dependent diabetes mellitus reveal glutamate decarboxylase as the target antigen. Proc. Natl. Acad. Sci. USA 89: 846-847, 1992.
130. Richter W., Seißler J., Wolfahrt S., Scherbaum W.A.: Human monoclonal islet specific autoantibodies share features of islet cell and 64 kDa antibodies. Diabetologia 36: 785-90, 1993.
131. Richter W., Shi Y., Bækkeskov S.: Autoreactive epitopes defined by diabetes-associated human monoclonal antibodies are localized in the middle and C-terminal domains of the smaller form of glutamate decarboxylase. Proc. Natl. Acad. Sci. USA 90: 2832-2836, 1993.
132. Ujihara N., Daw K., Gianani R., Boel E., Yu L., Powers A.C.: Identification of glutamic acid decarboxylase autoantibody heterogeneity and epitope regions in type I diabetes. Diabetes 43: 968-975, 1994.
133. Panina-Bordignon P., Lang R., van Endert P.M., Benazzi E., Felix A.M., Pastore R.M., Spinas G.A., Sinigaglia F.: Cytotoxic T cells specific for glutamic acid decarboylase in autoimmune diabetes. J. Exp. Med. 181: 1923-1927, 1995.
134. Hamson L.C., Honeyman M.C., Deaizpurua HJ., Schmidli R.S.. Colman P.C., Tait B.D.. Cram D.S.: Inverse regulation between humoral and cellular immunity to glutamic acid decarboxylase in subjects at risk of insulin-dependent diabetes. Lancet 341: 1365-1369, 1993
135. Richter W., Jury K.M., Loeffkr D., Manfras B.J., Eiermann T.H., Boehm B.O.: Immunoglobulin variable gene analysis of human autoantibodies reveals antigen-driven immune response to glutamate decarboxylase in type 1 diabetes mellitus. Eur. J. Immunol. 25: 1703-1712, 1995.
136. Sanjeevi C.B., Kockum I., Lernmark Å.: The role of major histocompatibility complex in insulin-dependent diabetes mellitus. Current Science 2: 3-11, 1995.
137. Sanjeevi C.B., Lybrand T.P., DeWeese C., Landin-Olsson M., Kockum I., Dahlquist G., Sundkvist G., Stenger D., Lernmark Å.: Polymorphic amino acid variations in HLA-DQ are associated with systematic physical property changes and occurrence of insulin-dependent diabetes mellitus. Diabetes 44: 125-131, 1995.
138. Sanjeevi C.B., Landin-Olsson M., Kockum I., Dahlquist G., Lernmark Å.: Effects of the second HLA-DQ haplotype on the association with childhood insulin dependent diabetes mellitus. Tissue Antigens 45: 148-152, 1994.
139. Thorsby E., Rønningen K.S.: Particular HLA-DQ molecules play a dominant role in determining susceptibility or resistance to Type 1 (insulin-dependent) diabetes mellitus. Diabetoiogia 36: 371-377, 1993.
140. Kockum I., Wassmuth R., Holmberg E., Michelsen B., Lernmark Å.: HLA-DQ primarily confers protection and HLA-DR susceptibility in Type 1 (insulin-dependent) diabetes studied in population-based affected families and controls. Am. J. Hum. Gen. 53: 150-167, 1993.
141. Reijonen H., Vahasalo P., Karjalainen J., Ilonen J., Akerblom H.K., Knip M.: HLA-DQB1 genotypes and islet cell antibodies in the identification of siblings at risk for insulin-dependent diabetes (IDDM) in Finland. Childhood Diabetes in Finland (DiMe) Study Group. J. Autoimmun. 1: 675-686, 1994.
142. Sanjeevi C.B.. Höök P., Landin-Olsson M., Kockum I., Dahlquist G., Lybrand T.P., Lernrnark Å.: DR4 subtypes and their molecular properties in a population based study of Swedish childhood diabetes. Tissue Antigens 47: 275-283, 1996.
143. Tait B.D., Drummond B.P., Varney M.D., Harrison L.C.: HLA-DRBI
144. Owerbach D., Gunn S., Gabbay K.H.: Primary association of HLA-DQw8 with type 1 diabetes in DR4 patients. Diabetes 38: 942-945, 1989.
145. Cucca F., Muntoni F., Lampis R., Frau F., Argiolas L., Silvetti M., Angius E., Cao A., DeVirgiliis S., Congia M.: Combinations of specific DRBI, DQA1, DQB1 haplotypes are associated with insulin-dependent diabetes mellitus in Sardinia. Human Immunol. 37: 85-94, 1993.
146. Serjeantson S.W., Court J., Mackay I.R., Matheson B., Rowley M.J., Tuomi T., Wilson J.D., Zimmet P.: HLA-DQ genotypes are associated with autoimmunity to glutamic acid decarboxylase in insulin-dependent diabetes mellitus patients. Human Immunol. 38: 97-104, 1994.
147. Kockum I., Sanjeevi C.B., Eastman S., Landin-Olsson M., Dahlquist G., Lernmark Å.: Population analysis of protection by HLA-DR and DQ genes protection from insulin-dependent diabetes mellitus in Swedish insulin-dependent diabetes children and controls. Eur. J. Immunogenetics 22: 443-465, 1995.
148. Baisch J.M., Weeks T., Giles R., Hoover M , Stastny P., Capra J.D.: Analysis of HLA-DQ genotypes and susceptibility in insulin-dependent diabetes mellitus. N. Eng. J. Med. 322: 1836-1882, 1990.
149. Sanjeevi C.B., Lybrand T.P., Landin-Olsson M., Kockum I., Dahlquist G., Hagopian W.A., Palmer J.P., Lernmark Å.: Analysis of antibody markers. DRB1, DRB5, DQA1 and DQB1 genes and modeling of DR2 molecules in DR2 positive patients with insulin-dependent diabetes mellitus. Tissue Antigens 44: 110-119, 1994.
150. Sanjeevi C.B., Falorni A., Kockum I., Hagopian W.A., Lernmark Å.: HLA and glutamic acid decarboxylase in human insulin-dependent diabetes mellitus. Diabetic Med 13: 209-217, 1996.
151. Atkinson M.A., Kaufman D.L., Campbell L., Gibbs K.A., Shah S.C., Bu D.-F., Erlander M.G., Tobin A.J., Maclaren N.K.: Response of peripheral-biood mononuclear cells to glutamate decarboxylase in insulin-dependent diabetes. Lancet 339: 458-459, 1992.
152. Atkinson M., Bowman M., Campbell L., Darrow B., Kaufman D.L., Maclaren N.K.: Cellular immunity to a determinant common to glutamate decarboxylase and Coxsackie virus in insulin dependent diabetes. J. Clin. Invest. 94: 2125-2129, 1994.
153. Lohmann T., Leslie R.D.G., Hawa M., Geysen M., Rodda S., Londei M.: Immunodominant epitopes of glutamic acid decarboxylase 65 and 67 in insulin-dependent diabetes mellitus. Lencet 343: 1607-1608, 1994.
154. Lernmark Å.: Glutamic acid decarboxylase - Gene to Antigen to Disease - GAD. J. Int. Med. in press: 1996.
155. Rudy G., Stone N., Harrison L.C., Colman P.G., McNair P., Brusic V., French M.B., Honeyman M.C., Tait B., Lew A.M.: Similar peptides from two beta cell autoantigens, proinsulin and glutamic acid decarboxyiase. stimulate T cells of individuals at risk for insulin-dependent diabetes. Mol. Med. 1: 625-633, 1995.
156. Kwok W.W., Domeier M.E., Raymond F.C., Byers P., Nepom G.T.: Allele-specific motifs characterize HLA-DQ interactions with a diabetes-associated peptide derived from glutamic acid decarboxylase. J. Immunol. in press: 1996.
157. Kwok W.W., Domeier M.E., Johnson M.L., Nepom G.T., Koelle D.M.: HLA-DQB1 codon 57 is critical for peptide binding and recognition. J. Exp. Med in press: 1996.
158. Tian J., Lehmann P.V., Kaufman D.L.: T cell cross-reactivity between Coxsackie virus and glutamate decarboxylase is associated with a murine diabetes susceptibility allele. J. Exp. Med 180: 1979-1984, 1994.
159. Gamble D.R.: The epidemiology of insulin-dependent diabetes, with particular reference to the relationship of virus infection to its etiology. Epidemiol. Rev. 2: 49-70, 1980.
160. Yoon J.-W., Ray U.R.: Perspectives on the role of viruses in insulin-dependent diabetes. Diabetes Care 8: 39-44, 1985.
161. Damian R.T.: Parasites and molecular mimicry. In: Lernmark Å., Dyrberg T., Terenius L., Hökfelt B. (Eds) Molecular Mimicry in Health and Disease. Elsevier Science Publishers, Amsterdam, 1988, pp. 211-218.
162. Hou J., Sheikh S., Martin D.L., Chatterjee N.K.: Coxsackie virus B4 alters pancreatic glutamate decarboxylase expression in mice soon after infection. J. Autoimmun. 6: 529-542, 1993.
163. Hou J., Said C. Franchi D., Dockstader P., Chatterjee N.K.: Antibodies to glutamic acid decarboxylase and P2-C peptides in sera from Coxsackie virus B4-infected mice and IDDM patients. Diabetes 43: 1260-1266, 1994.
164. Richter W., Mertens T., Schoel B., Muir P., Ritzkowsky A., Scherbaum W. A., Boehm B.: Sequence homology of the disease-associated autoantigen glutamate decarboxvlase with Coxsackie B4-2C protein and heat shock protein 60 mediates no molecular mimicry of autoantibodies. J. Exp. Med. 180: 721-726, 1994.
165. Pleau J.M., Fernandez S.F., Esling A., Homo D.F., Dardenne M.: Prevention of autoimmune diabetes in nonobese diabetic female mice by treatment with recombinant glutamic acid decarboxylase (GAD 65). Clin. Immunol. Immunopathol. 76: 90-95, 1995.
166. 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 diabetes. Nature 366: 6'9-72, 1993.
167. Petersen J.S., Karlsen A.E., Markholst H., Worsaae A., Dyrberg T., Michelsen B.: Neonatal tolerization with glutamic acid decarboxytase but not with bovine serum albumin delays the onset of diabetes in NOD mice. Diabetes 43: 14781484, 1994.
168. Bieg S., Möller C., Olsson T., Lernmark Å.: In situ hybridization reveals lyp genotype-associated cytokine expression in BB rats. Annual Conference on Clinical Immunology. New Orleans, L.A.: Clinical Immunology Society. 42, 1996. (Abstract).
169. Romagnani S.: Human TH1 andTH2 subsets: regulation of differentiation and role in protection and immunopathology. Int. Arch. Allergy Immunol 98: 279-285, 1992.
170. Gianani R., Pugliese A., Bonner-Weir S., Shiffrin A.J., Soeldner J.S., Erlich H., Awdeh Z., Slper C.A., Jackson R.A., Eisenbarth G.S.: Prognostically significant heterogeneity of cytoplasmic islet cell antibodies in relatives of patients with type 1 diabetes. Diabetes 41: 347-353, 1992.
171. Verge C.F., Gianani R., Yu L., Pietropaolo M., Smith T., Jackson R.A., Soeldner J.S., Eisenbarth G.S.: Late progression to diabetes and evidence for chronic beta-cell autoimmunity in identical twins of patients with type I diabetes. Diabetes 44: 1176-1179, 1995.
172. Weiner H.L., Miller A., Khoury S.J., Zhang Z.J., al S.A., Brod S.A., Lider O., Higgins P., Sobel R., Matsui M., et al.: Treatment of autoimmune diseases by oral tolerance to autoantigens. Adv. Exp. Med. Biol. 1217-1223, 1995.
173. Trentham D.E., Dynesius T.R.A., Orav E.J., Combitchi D., Lorenzo C., Seweli K.L., Hafler D.A., Weiner H.L.: Effects of oral administration of type II collagen on rheumatoid arthritis [see comments]. Science 261: 1727-1730, 1993.
174. Wegmann D.R., Gill R.G., Daniel D.: The role of insulin-specific T cells in IDDM in NOD mice. Proceedings 13th Immunology and Diabetes Workshop. Montvillargenne, France: 1994: 12 (Abstract).