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Multiple genes/multiple autoantigens role in type 1 diabetes

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Conclusion

We hypothesize that Type 1 diabetes of humans and NOD mouse results from non-MHC genes, which determine susceptibility to T-cell autoimmunity. MHC class II alleles (and perhaps class I) determines the tissue targeted by these T-cells (DQ8/DQ2 Type 1 diabetes and Addison's disease, DQ2 or DQ8 for celiac disease). The high propensity for islet beta cells to be the target of autoimmunity we believe is the result of a peculiarity of the insulin B-chain peptide, such that it is a dominant beta cell-specific autoantigen. In the NOD mouse, autoreactive T-cells show a restricted Vα repertoire. The ability of selected class II molecules to prevent disease may relate to effects of these molecules (I-E, DQB1*0602, and so forth) on the T-cell repertoire. With improving assays for autoantibodies and T-cell autoimmunity and the availability of transgenic mouse, we believe that the aforementioned hypotheses can be thoroughly tested.

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References

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

    Article  PubMed  CAS  Google Scholar 

  2. Bach J-F. Insulin-dependent diabetes mellitus as an autoimmune disease. Endocr Rev 1994; 15:516–542.

    Article  PubMed  CAS  Google Scholar 

  3. Nepom GT. Immunogenetics and IDDM. Diabetes Rev 1993; 1:93–103.

    Google Scholar 

  4. Eisenbarth GS, Ziegler A. Type I Diabetes Mellitus. In: Weintraub BD (ed.) Molecular Endocrinology: Basic concepts and Clinical Correlations. 1st ed. New York: Raven Press, 1995, pp. 269–282.

    Google Scholar 

  5. Bellgrau D, Pugliese A. NOD mouse and BB rat: genetics and immunologic function. In: Eisenbarth GS, Lafferty KJ (eds.) Type I Diabetes: Molecular, Cellular, and Clinical Immunology. 1st ed New York, New York: Oxford University Press, 1996, pp. 53–75.

    Google Scholar 

  6. Redondo MJ, Rewers M, Jackson R, Yu L, Garg S, Pilcher CC, et al. Anti-islet autoimmunity is primarily genetically determined as evidenced by autoanti-body expression of monozygotic twins, dizygotic twins and siblings of patients with type I diabetes: a prospective case-control study. BMJ 1999; 318:698–702.

    PubMed  CAS  Google Scholar 

  7. Davies JL, Kawaguchi Y, Bennett ST, Copeman JB, Cordell HJ, Pritchard LE, et al. A genome-wide search for human type 1 diabetes susceptibility genes. Nature 1994; 371:130–136.

    Article  PubMed  CAS  Google Scholar 

  8. Kawasake E, Noble J, Erlich H, Mulgrew CL, Fain PR, Eisenbarth GS. Transmission of DQ haplotypes to patients with type 1 diabetes. Diabetes 1998; 47:1971–1973.

    Article  Google Scholar 

  9. Morel PA, Dorman JS, Todd JA, McDevitt HO, Trucco M. Aspartic acid at position 57 of the HLA-DQ beta chain protects against type I diabetes: a family study. Proc Natl Acad Sci USA 1988; 85:8111–8115.

    Article  PubMed  CAS  Google Scholar 

  10. Todd JA, Bell JI, McDevitt HO. HLA-DQB gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 1987; 329:599–604.

    Article  PubMed  CAS  Google Scholar 

  11. Baisch JM, Weeks T, Giles R, Hoover M, Stastny P, Capra JD. Analysis of HLA-DQ genotypes and susceptibility in insulin-dependent diabetes mellitus. N Engl J Med 1990; 322:1836–1841.

    Article  PubMed  CAS  Google Scholar 

  12. Rewers M, Bugawan TL, Norris JM, Blair A, Beaty B, Hoffman M, et al. Newborn screening for HLA markers associated with IDDM: diabetes autoimmunity study in the young (DAISY). Diabetologia 1996; 39:807–812.

    Article  PubMed  CAS  Google Scholar 

  13. Fain, P, Eisenbarth, GS. Genetics of type 1 diabetes mellitus. In: Baxter J, Melmed S, New M, Martin L (eds.) Geneticus in Endocrinology. Lippincott-Raven, Philadephia, PA, 1999.

    Google Scholar 

  14. Pugliese A, Zeller M, Fernandez A, Zalcberg LJ, Bartlett RJ, Ricordi C, et al. The insulin gene is transcribed in the human thymus and transcription levels correlate with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type I diabetes. Nat Genet 1997; 15:293–297.

    Article  PubMed  CAS  Google Scholar 

  15. Bennett ST, Lucassen AM, Gough SCL, Powell EE, Undlien DE, Pritchard LE, et al. Suspectibility to human type I diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus. Nat Genet 1995; 9:284–292.

    Article  PubMed  CAS  Google Scholar 

  16. Bennett ST, Wilson AJ, Cucca F, Nerup J, Pociot F, McKinney PA, et al. IDDM2-VNTR-encoded suspectibility to type 1 diabetes: dominant protection and parental transmission of alleles of the insulin gene-linked minisatellite locus. J. Autoimmun 1996; 9:415–421.

    Article  PubMed  CAS  Google Scholar 

  17. Pugliese A, Awdeh ZL, Alper CA, Jackson RA, Eisenbarth GS. The paternally inherited insulin gene B allele (1,428 FokI site) confers protection from insulin-dependent diabetes in families. J Autoimmun 1994; 7:687–694.

    Article  PubMed  CAS  Google Scholar 

  18. Lernmark Å, Ott J. Sometimes it's hot, sometimes it's not. Nat Genet 1998; 19:213, 214.

    Article  PubMed  CAS  Google Scholar 

  19. Concannon, P, Gogolin-Ewens KJ, Hinds DA, Wapelhorst B, Morrison VA, Stirling B, et al. A second-generation screen of the human genome for susceptibility to insulin-dependent diabetes mellitus. Nat Genet 1998; 19:292–296.

    Article  PubMed  CAS  Google Scholar 

  20. Mein CA, Esposito L, Dunn MG, Johnson GCL, Timms AE, Goy JV, et al. A search for type 1 diabetes susceptibility genes in families from the United Kingdom. Nat Genet 1998; 19:297–300.

    Article  PubMed  CAS  Google Scholar 

  21. Verge CF, Vardi P, Babu S, Bao F, Erlich HA, Bugawan T, et al. Evidence for oligogenic inheritance of type 1A diabetes in a large Bedouin Arab family. J Clin Invest 1998; 102:1569–1575.

    PubMed  CAS  Google Scholar 

  22. Betterle C, Volpato M, Rees Smith B, Furmaniak J, Chen S, Zanchetta R, et al. II. Adrenal cortex and steroid 21-hydroxylase autoantibodies in children with organ-specific autoimmune diseases: markers of high progression to clinical Addison's disease. J Clin Endocrinol Metab 1997; 82:939–942.

    Article  PubMed  CAS  Google Scholar 

  23. Falorni A, Laureti S, Nikoshkov A, Picchio ML, Hallengren B, Vandewalles CL, et al. 21-hydroxylase autoantibodies in adult patients with endocrine autoimmune diseases are highly specific for Addison's disease. Clin Exp Immunol 1997; 107:341–346.

    Article  PubMed  CAS  Google Scholar 

  24. Chen S, Sawicka J, Betterle C, Powell M, Prentice L, Volpato M, et al. Autoantibodies to steroidogenic enzymes in autoimmune polyglandular syndrome, Addison's disease, and premature ovarian failure. J Clin Endocrinol Metab 1996; 81:1871–1876.

    Article  PubMed  CAS  Google Scholar 

  25. Yu L, Brewer, KW, Gates S, Wang T, Babu S, Gottlieb PA, et al. DRB1*04 and DQ alleles: expression of 21-hydroxylase autoantibodies and risk of progression to Addison's disease. J Clin Endocrinol Metab 1999; 84:328–335.

    Article  PubMed  CAS  Google Scholar 

  26. Petronzelli F, Multari G, Ferrante P, Bonamico M, Rabuffo G, Campea L, et al. Different dose effect of HLA-DQαβ heterodimers in insulin-dependent diabetes mellitus and celiac disease susceptibility. Hum Immunol 1993; 36:156–162.

    Article  PubMed  CAS  Google Scholar 

  27. Carter C, Sheldon W, Walker C. The inheritance of coeliac disease. Ann Hum Genet 1959; 23:266–278.

    PubMed  CAS  Google Scholar 

  28. Bao F, Yu L, Babu S, Wang T, Hoffenberg EJ, Rewers M, Eisenbarth GS. One third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease associated to transglutaminase autoantibodies. J Autoimmune 1999; 13:143–148.

    Article  CAS  Google Scholar 

  29. Yu L, Eisenbarth GS. Immunology of type 1 diabetes and related endocrine disorders. Clin Endocrinol 1998; 257–266.

  30. Bottazzo GF, Florin-Christensen A, Doniach D. Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet 1974; 2:1279–1283.

    Article  PubMed  CAS  Google Scholar 

  31. Falorni A, Örtqvist E, Persson B, Lernmark Å. Radioimmunoassays for glutamic acid decarboxylase (GAD65) and GAD65 autoantibodies using 35S or 3H recombinant human ligands. J Immunol Methods 1995; 186:89–99.

    Article  PubMed  CAS  Google Scholar 

  32. Kaprio J, Tuomilehto J, Koshenvuo M, Romanov K, Reunanen A, Eriksson J, et al. Concordance for type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland. Diabetologia 1993; 35:1060–1067.

    Article  Google Scholar 

  33. Rabin DU, Pleasic SM, Palmer-Crocker R, Shapiro JA. Cloning and expression of IDDM-specific human autoantigens. Diabetes 1992; 41:183–186.

    Article  PubMed  CAS  Google Scholar 

  34. Gianani R, Rabin DU, Verge CF, Yu L, Babu S, Pietropaolo M, et al. ICA512 autoantibody radioassay. Diabetes 1995; 44:1340–1344.

    Article  PubMed  CAS  Google Scholar 

  35. Lan MS, Lu J, Goto Y, Notkins AL. Molecular cloning and identification of a receptor-type protein tyrosine phosphatase, IA-2, from human insulinoma. DNA Cell Biol 1994; 13:505–514.

    Article  PubMed  CAS  Google Scholar 

  36. Zhang B, Lan MS, Notkins AL. Autoantibodies to IA-2 in IDDM: location of major antigenic determinants. Diabetes 1997; 46:40–43.

    Article  PubMed  Google Scholar 

  37. Christie MR. Islet cell autoantigens in type I diabetes. Eur J Clin Invest 1996; 26:827–838.

    PubMed  CAS  Google Scholar 

  38. Pietropaolo M, Hutton JC, Eisenbarth GS. Protein tyrosine phosphatase-like proteins: link with IDDM. Diabetes Care 1996; 20:208–214.

    Google Scholar 

  39. Greenbaum CJ, Palmer JP. Humoral immune markers: insulin antibodies. In: Palmer JP (ed.) Prediction, Prevention, and Genetic Counseling in IDDM. Chichester, England: Wiley, 1996, pp. 63–76.

    Google Scholar 

  40. Naserke HE, Dozio N, Ziegler A-G, Bonifacio E. Comparison of a novel microassay for insulin autoantibodies with the conventional radiobinding assay. Diabetologia 1998; 41:681–683.

    Article  PubMed  CAS  Google Scholar 

  41. Aanstoot H-J, Kang S-M, Kim J, Lindsay L Roll U, Knip M, et al. Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type I diabetes. J Clin Invest 1996; 97:2772–2783.

    PubMed  CAS  Google Scholar 

  42. Atkinson MA, Maclaren NK. Islet cell autoantigens in insulin-dependent diabetes. J Clin Invest 1993; 92:1608–1616.

    PubMed  CAS  Google Scholar 

  43. Gianani R, Eisenbarth GS. Humoral autoimmunity. In: Eisenbarth GS, Lafferty KJ, (eds.) Type I Diabetes: Molecular, Cellular, and Clinical Immunology. 1st ed. New York City, New York: Oxford University Press, 1996:209–229.

    Google Scholar 

  44. Martin S, Lampasona V, Dosch M, Pietropaolo M. Islet cell autoantigen 69 antibodies in IDDM. Diabetologia 1996; 39:747.

    Article  PubMed  CAS  Google Scholar 

  45. Elias D, Cohen IR. Treatment of autoimmune diabetes and insulitis in NOD mice with heat shock protein 60 peptide p277. Diabetes 1995; 44:1132–1138.

    Article  PubMed  CAS  Google Scholar 

  46. Mcevoy RC, Thomas NM, Ness J. Humoral immune markers: additional islet cell antigens: important clues to pathogenesis or red herrings? In: Palmer JP (ed.) Prediction, Prevention, and Genetic Counseling in IDDM. Chichester, England: Wiley, 1996:97–108.

    Google Scholar 

  47. Buschard K, Josefsen K, Horn T, Fredman P. Sulphatide and sulphatide antibodies in insulin-dependent diabetes mellitus Lancet 1993; 342:840.

    Article  PubMed  CAS  Google Scholar 

  48. Dotta F, Gianani R, Previti M, Lenti L, Dionisi S, D'Erme M, et al. Autoimmunity to the GM2-1 islet ganglioside before and at the onset of type I diabetes. Diabetes 1996; 45:1193–1196.

    Article  PubMed  CAS  Google Scholar 

  49. Eisenbarth GS. Combinatorial autoantibody screening for prediction of type I diabetes. Clin Res 1993; 41:154A Abstract.

    Google Scholar 

  50. Bingley PJ, Christie MR, Bonifacio E, Bonfanti R, Shattock M, Fonte M-T, et al. Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives. Diabetes 1994; 43:1304–1310.

    Article  PubMed  CAS  Google Scholar 

  51. 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; 45:926–933.

    Article  PubMed  CAS  Google Scholar 

  52. Eisenbarth GS, Gianani R, Yu L, Pietropaolo M, Verge CF, Chase HP, et al. Dual parameter model for prediction of type 1 diabetes mellitus. Proc Assoc Am Physicians 1998; 110:126–135.

    PubMed  CAS  Google Scholar 

  53. Haskins K, Wegmann D. Diabetogenic T-cell clones. Diabetes 1996; 45:1299–1305.

    Article  PubMed  CAS  Google Scholar 

  54. Wegmann DR, Norbury-Glaser M, Daniel D. Insulin-specific T cells are a predominant component of islet infiltrates in pre-diabetic NOD mice. Eur J Immunol 1994; 24:1853–1857.

    Article  PubMed  CAS  Google Scholar 

  55. Wegmann DR, Gill RG, Norbury-Glaser M, Schloot N, Daniel D. Analysis of the spontaneous T cell response to insulin in NOD mice. J Autoimmun 1994; 7:833–843.

    Article  PubMed  CAS  Google Scholar 

  56. Daniel D, Gill RG, Schloot N, Wegmann D. Epitope specificity, cytokine production profile and diabetogenic activity of insulin-specific T cell clones isolated from NOD mice. Eur J Immunol 1995; 25:1056–1062.

    Article  PubMed  CAS  Google Scholar 

  57. Simone E, Daniel D, Schloot N, Gottlieb P, Babu S, Kawasaki E, et al. T cell receptor restriction of diabetogenic autoimmune NOD T cells. Proc Natl Acad Sci USA 1997; 94:2518–2521.

    Article  PubMed  CAS  Google Scholar 

  58. Daniel D, Wegmann DR. Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous administration of insulin peptide B-(9–23). Proc Natl Acad Sci U S A 1996; 93:956–960.

    Article  PubMed  CAS  Google Scholar 

  59. Zekzer D, Wong FS, Wen L, Altieri M, Gurlo T, von Grafenstein H, et al. Inhibition of diabetes by an insulin-reactive CD4 T-cell clone in the nonobese diabetic mouse. Diabetes 1997; 46:1124–1132.

    Article  PubMed  CAS  Google Scholar 

  60. Atkinson MA, Bowman MA, Kuo-Jang K, Campbell L, Dush PJ, Shah SC, et al. Lack of immune responsiveness to bovine serum albumin in insulin-dependent diabetes. N Engl J Med 1993; 329:1853–1858.

    Article  PubMed  CAS  Google Scholar 

  61. Atkinson MA, Bowman MA, Campbell L, Darrow BL, Kaufman DL, Maclaren NK. Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes. J Clin Invest 1994; 94:2125–2129.

    PubMed  CAS  Google Scholar 

  62. Durinovic-Bello I, Hummel M, Ziegler AG. Cellular immune response to diverse islet cell antigens in IDDM. Diabetes 1996; 45:795–800.

    Article  PubMed  CAS  Google Scholar 

  63. Brooks-Worrell BM, Starkebaum GA, Greenbaum C, Palmer JP. Peripheral blood mononuclear cells of insulin-dependent diabetic patients respond to multiple islet cell proteins. J Immunol 1996; 157:5668–5674.

    PubMed  CAS  Google Scholar 

  64. Endl J, Otto H, Jung G, Dreisbusch B, Donie F, Stahl P, et al. Identification of naturally processed T cell epitopes from glutamic acid decarboxylase presented in the context of HLA-DR alleles of T lymphocytes of recent onset IDDM patients. J Clin Invest 1997; 99:2405–2415.

    PubMed  CAS  Google Scholar 

  65. Schloot NC, Roep BO, Wegmann DR, Yu L, Wang TB, Eisenbarth GS. T cell reactivity to GAD65 peptide sequences shared with coxsackie virus protein in recent-onset IDDM patients and control subjects. Diabetologia 1997; 40:332–338.

    Article  PubMed  CAS  Google Scholar 

  66. Schloot NC, Roep BO, Wegmann DR, Yu L, Chase P, Wang T, et al. Altered immune response to insulin to newly diagnosed compared to insulin-treated diabetic patients and health control subjects. Diabetologia 1997; 40:564–572.

    Article  PubMed  CAS  Google Scholar 

  67. Pugliese A, Bugawan T, Moromisato R, Awdeh ZL, Alper CA, Jackson RA, et al. 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; 2447–2452.

  68. Castano L, Ziegler, AG, Ziegler R, Shoelson S, Eisenbarth GS. Characterization of insulin autoantibodies in relatives of patients with type 1 diabetes. Diabetes 1993; 42:1202–1209.

    Article  PubMed  CAS  Google Scholar 

  69. Keller RJ, Eisenbarth GS, Jackson RA. Insulin prophylaxis in individuals at high risk of type I diabetes. Lancet 1993; 341:927,928.

    Google Scholar 

  70. Eisenbarth GS, Jackson RA, Pugliese A. Insulin autoimmunity: the rate limiting factor in pre-type I diabetes. J Autoimmun 1992; 5(suppl A):241–246.

    Article  PubMed  Google Scholar 

  71. Ziegler AG, Ziegler R, Vardi P, Jackson RA, Soeldner JS, Eisenbarth GS. Life table analysis of progression to diabetes of anti-insulin autoantibody-positive relatives of individuals with type I diabetes. Diabetes 1989; 38:1320–1325.

    Article  PubMed  CAS  Google Scholar 

  72. Vardi P, Ziegler AG, Matthews 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; 11:736–739.

    PubMed  CAS  Google Scholar 

  73. Petersen JS, Russel S, Marshall, MO, Kofod H, Buschard K, Cambon N, et al. Differential expression of glutamic acid decarboxylase in rat and human islets. Diabetes 1993; 42:484–495.

    Article  PubMed  CAS  Google Scholar 

  74. Julier C, Hyer, RN, Davies J, Merlin F, Soularue P, Briant L, et al. Insulin-IGF2 region on chromosome 11p encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility. Nature 1991; 354:155–159.

    Article  PubMed  CAS  Google Scholar 

  75. Lucassen AM, Julier C, Beressi J-P, Boitard C, Froguel P, Lanthrop M, et al. Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR. Nat Genet 1993; 4:305–310.

    Article  PubMed  CAS  Google Scholar 

  76. Owerbach D, Gabbay KH. Localization of a type 1 diabetes susceptibility locus to the variable tandem repeat region flanking the insulin gene. Diabetes 1993; 42:1708–1714.

    Article  PubMed  CAS  Google Scholar 

  77. Tompkins SM, Moore JC, Jensen PE. An insulin peptide that binds an, alternative site in class II major histocompatibility complex. J Exp Med 1996; 183:857–866.

    Article  PubMed  CAS  Google Scholar 

  78. Zhang ZJ, Davidson L, Eisenbarth G, Weiner HL. Suppression of diabetes in nonobese diabetic mice by oral administration of porcine insulin. Proc Natl Acad Sci USA 1991; 88:10,252–10,256.

    CAS  Google Scholar 

  79. Bergerot I, Fabien N, Maguer V, Thivolet C. Oral insulin induces CD4+ regulatory cells that protect NOD mice from adoptive transfer of diabetes. J Immunol 1994; Abstract.

  80. Harrison LC, Dempsey-Collier M, Kramer DR, Takahashi K. Aerosol insulin induces regulatory CD8 gamma delta T cells that prevent murine insulin-dependent diabetes. J Exp med 1996; 184:2167–2174.

    Article  PubMed  CAS  Google Scholar 

  81. Muir A, Peck A, Clare-Salzler M, Song Y-H, Cornelius J, Luchetta R, et al. Insulin immunization of nonobese diabetic mice induces a protective insulitis characterized by diminished intraislet interferon-gamma transcription. J Clin Invest 1995; 95:628–634.

    Article  PubMed  CAS  Google Scholar 

  82. Karounos DG, Bryson JS, Colhen DA. Metabolically inactive insulin analog prevents type I diabetes in prediabetic NOD mice. J Clin Invest 1997; 100:1344–1348.

    PubMed  CAS  Google Scholar 

  83. Hartmann B, Bellmann K, Ghiea I, Kleemann R, Kolb H. Oral insulin for diabetes prevention in NOD mice: potentiation by enhancing Th2 cytokine expression in the gut through bacterial adjuvant. Diabetologia 1997; 40:902–909.

    Article  PubMed  CAS  Google Scholar 

  84. Hancock WW, Polansky M, Zhang J, Blogg N, Weiner, HL. Suppression of insulitis in non-obese diabetic (NOD) mice by oral insulin administration is associated with selective expression of interleukin-4 and-10, transforming growth factor-beta, and prostaglandin-E. Am J Pathol 1995; 147:1193–1199.

    PubMed  CAS  Google Scholar 

  85. Cetkovic-Cvrlje M, Gerling IC, Muir A, Atkinson MA, Elliott JF, Leiter EH. Retardation or acceleration of diabetes in NOD/Lt mice mediated by intrathymic administration of candidate β-cell antigens. Diabetes 1997; 46:1975–1982.

    Article  PubMed  CAS  Google Scholar 

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  1. Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, CO

    Norio Abiru & George S. Eisenbarth

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Abiru, N., Eisenbarth, G.S. Multiple genes/multiple autoantigens role in type 1 diabetes. Clinic Rev Allerg Immunol 18, 27–40 (2000). https://doi.org/10.1385/CRIAI:18:1:27

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