#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Genetic and molecular background in autoimmune diabetes mellitus


Authors: D. Kantárová 1,2;  D. Prídavková 1;  I. Ságová 1;  M. Vrlík 2;  J. Mikler 3;  M. Buc 4
Authors‘ workplace: I. interná klinika JLF UK a UNM, Martin, Slovensko 1;  Martinské centrum imunológie, Martin, Slovensko 2;  Klinika detí a dorastu JLF UK a UNM, Martin, Slovensko 3;  Imunologický ústav LF UK, Bratislava, Slovensko SÚHRN 4
Published in: Epidemiol. Mikrobiol. Imunol. 64, 2015, č. 3, s. 121-129
Category: Review Article

Overview

Type 1 diabetes mellitus (T1 DM) is caused by autoimmune-mediated and idiopathic beta-cell destruction of the pancreatic islets of Langerhans resulting in absolute insulin deficiency. Susceptibility to T1 DM is influenced by both genetic and environmental factors. It is generally believed that in genetically susceptible individuals, the disease is triggered by environmental agents, such as viral infections, dietary factors in early infancy, or climatic influences. Many candidate genes for diabetes have been reported; those within the Major Histocompatibility Complex being among the most important. The most common autoantigens are insulin, glutamic acid decarboxylase 65, insuloma-associated antigen 2, and zinc transporter ZnT8. The destruction of b-cells is mediated mainly by cellular mechanisms; antibodies only seem to reflect the ongoing autoimmune processes and are not directly involved in the tissue damage. They, however, appear prior to the onset of insulin deficiency which makes them suitable for use in the prevention of the disease.

Keywords:
autoantigens – autoantibodies – HLA alleles – insuline – B, T, and NKT cells


Sources

1. TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY) Study. Ann New York Acad Scie, 2008;1150:1-13.

2. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care, 2010;33(Suppl 1):S62–S69.

3. Hanafusa T, Imagawa A. Insulitis in human type 1 diabetes. Ann New York Acad Scie, 2008;1150:297–299.

4. American Diabetes Association. Standards of Medical Care in Diabetes – 2014. Diabetes Care, 2014; 37(S1):S14–S80.

5. Aguilera E, Casamitjana R, Ercilla G, et al. Adult-onset atypical (type 1) diabetes: additional insigh ts and differences with type 1A diabetes in a European Mediterranean population. Diabetes Care, 2004;27(5):1108–1114.

6. Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment, Lancet, 2001:358(9277):221–229.

7. Todd JA, Knip M, Mathieu C. Strategies for the prevention of autoimmune type 1 diabetes. Diabet Med., 2011;28(10):1141–1143.

8. Kantarova D, Buc M. Genetic susceptibility to type 1 diabetes mellitus in humans. Physiological research, 2007;56(3):255–266.

9. Todd JA. Etiology of type 1 diabetes. Immunity, 2010;32(4):457–467.

10. Maier LM, Wicker LS. Genetic susceptibility to type 1 diabetes. Curr Opin Immunol, 2005;17(6):601–608.

10. Concannon P, Rich SS, Nepom GT. Genetics of type 1A diabetes. New Engl J Med, 2009;360(16):1646–1654.

11. Zoka A, Muzes G, Somogyi A, et al. Altered Immune Regulation in Type 1 Diabetes. Clin Develop Immunol, 2013;254874.

12. Buc M, Bucova M, Javor J, et al. Associations between HLA class II alleles and type 1 diabetes mellitus in the Slovak population. Endocr Regul, 2006;40(1):1–6.

13. Morran MP, Vonberg A, Khadra A, Pietropaolo M. Immunogenetics of type 1 diabetes mellitus. Mol Aspects Med., 2015; doi: 10.1016/j.mam.2014.12.004

14. Concannon P, Erlich HA, Julier C, et al. Type 1 diabetes: evidence for susceptibility loci from four genome-wide linkage scans in 1,435 multiplex families. Diabetes, 2005;54(10):2995–3001.

15. Ziegler AG, Nepom GT. Prediction and pathogenesis in type 1 diabetes. Immunity, 2010;32(4):468–478.

16. Stuchlikova M, Kantarova D, Michalkova D, et al. Association of HLA-DPB1 alleles with type I diabetes mellitus in Slovak population. Bratisl Lek Listy, 2006;107(3):73–75.

17. Noble JA, Valdes AM, Thomson G, Erlich HA. The HLA class II locus DPB1 can influence susceptibility to type 1 diabetes. Diabetes, 2009;49(1):121–125.

18. Valdes AM, Noble JA, Genin E, et al. Modeling of HLA class II susceptibility to Type I diabetes reveals an effect associated with DPB1. Genetic Epidemiol, 2001;21(3):212–223.

19. Tsai, S., Santamaria, P. MHC Class II Polymorphisms, Autoreactive T-Cells, and Autoimmunity. Front Immunol, 2013;4(321):Epub 2013/10/18.

20. Santamaria P. The long and winding road to understanding and conquering type 1 diabetes. Immunity, 2010;32(4):437–445.

21. Durinovic-Bello I, Wu RP, Gersuk VH, et al. Insulin gene VNTR genotype associates with frequency and phenotype of the autoimmune response to proinsulin. Genes Immunity, 2010;11(2):188–193.

22. Ueda H, Howson JM, Esposito L, et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature, 2003;423(6939):506–511.

23. Atabani SF, Thio CL, Divanovic S, et al. Association of CTLA4 polymorphism with regulatory T cell frequency. Eur J Immunol, 2005;35(7):2157–2162.

24. Bottini N, Musumeci L, Alonso A, et al. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nature genetics, 2004;36(4):337–338.

25. Smyth D, Cooper JD, Collins JE, et al. Replication of an associa-tion between the lymphoid tyrosine phosphatase locus (LYP//PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus. Diabetes, 2004;53(11):3020–3023.

26. Long SA, Cerosaletti K, Bollyky PL, et al. Defects in IL-2R signaling contribute to diminished maintenance of FOXP3 expression in CD4(+)CD25(+) regulatory T-cells of type 1 diabetic subjects. Diabetes, 2010;59(2):407–415.

27. Vella A, Cooper JD, Lowe CE, et al. Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms. Am J Hum Genet, 2005;76(5):773–779.

28. Dendrou CA, Wicker LS. The IL-2/CD25 pathway determines susceptibility to T1D in humans and NOD mice. J Clin Immunol, 2008;28(6):685–696.

29. Dendrou CA, Plagnol V, Fung E, et al. Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource. Nature Genet, 2009;41(9):1011–1015.

30. Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol, 2010;10(7):490–500.

31. Zervou MI, Mamoulakis D, Panierakis C, et al. STAT4: a risk factor for type 1 diabetes? Human Immunol, 2008;69(10),647–650.

32. Korman BD, Alba MI, Le JM, et al. Variant form of STAT4 is associated with primary Sjogren’s syndrome. Genes Immunity, 2008;9(3):267–270.

33. Sandor F, Buc M. Toll-like receptors. I. Structure, function and their ligands. Folia Biol, 2005;51(5):148–157.

34. Swiecki M, McCartney SA, Wang Y, Colonna M. TLR7/9 versus TLR3/MDA5 signaling during virus infections and diabetes. J Leukocyte Bio, 2011;90(4):691–701.

35. Svoren BM, Volkening LK, Wood JR, Laffel LM. Significant vitamin D deficiency in youth with type 1 diabetes mellitus. J Pediatrics, 2009;154(1):132–134.

36. Winkler C, Lauber C, Adler K, et al. An interferon-induced helicase (IFIH1) gene polymorphism associates with different rates of progression from autoimmunity to type 1 diabetes. Diabetes, 2011;60(2):685–690.

37. Witso E, Tapia G, Cinek O, et al. Polymorphisms in the innate immune IFIH1 gene, frequency of enterovirus in monthly fecal samples during infancy, and islet autoimmunity. PloS One, 2011;6(11):e27781.

38. Anagandula M, Richardson SJ, Oberste MS, et al. Infection of human islets of langerhans with two strains of coxsackie B virus serotype 1: Assessment of virus replication, degree of cell death and induction of genes involved in the innate immunity pathway. J Med Virol, 2014, 86(8):1402–1411.

39. Salminen K, Sadeharju K, Lonnrot M, et al. Enterovirus infections are associated with the induction of beta-cell autoimmunity in a prospective birth cohort study. J Med Virol, 2003;69(1):91–98.

40. Yoon JW, Austin M, Onodera T, Notkins AL. Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. New Engl J Med, 1979;300(21):1173–1179.

41. Kukreja A, Maclaren NK. Autoimmunity and diabetes. J Clin Endocrinol Metabolism, 1999:84(12):4371–4378.

42. Todd JA, Bell JI, McDevitt HO. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature, 1987;329(6140):599–604.

43. Cucca F, Muntoni F, Lampis R, et al. Combinations of specific DRB1, DQA1, DQB1 haplotypes are associated with insulin-dependent diabetes mellitus in Sardinia. Human Immunol, 1993;37(2):85–94.

44. Horwitz, M.S., Bradley, L.M., Harbertson, J., Krahl, T., Lee, J., Sarvetnick, N. Diabetes induced by Coxsackie virus: initiation by bystander damage and not molecular mimicry. Nat Med, 1998;4(7):781–785.

45. Heino L, Lonnrot M, Knip M, et al. No evidence of abnormal regulation of antibody response to coxsackievirus B4 antigen in prediabetic children. Clin Exp Immunol, 2001;126(3):432–436.

46. Hoe E, McKay FC, Schibeci SD, et al. Functionally significant dif-ferences in expression of disease-associated IL-7 receptor alpha haplotypes in CD4 T cells and dendritic cells. J Immunol, 2010;184(5):2512–2517.

47. Smyth DJ, Plagnol V, Walker NM, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. New Engl J Med, 2008;359(26):2767–2777.

48. Stadinski B, Kappler J, Eisenbarth GS. Molecular targeting of islet autoantigens. Immunity, 2010;32(4):446–456.

49. Eisenbarth GS. Type I diabetes mellitus. A chronic autoimmune disease. New Engl J Med, 1986;314(21):1360–1368.

50. Haskins K, Bradley B, Powers K, et al. Oxidative stress in type 1 diabetes. Ann New York Acad Scie, 2003;1005:43–52.

51. Achenbach P, Bonifacio E, Ziegler AG. Predicting type 1 diabetes. Curr Diabetes Rep, 2005;5(2):98–103.

52. Kent SC, Chen Y, Bregoli L, et al. Expanded T cells from pan-creatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope. Nature, 2005;435(7039):224–228.

53. Anderson MS, Bluestone JA. The NOD mouse: a model of immune dysregulation. Ann Revi Immunol, 2005;23:447–485.

54. Culina S, Brezar V, Mallone R. Insulin and type 1 diabetes: immune connections. Eur J Endocrinol., 2013; 168(2):R19–31.

55. Miyazaki A, Hanafusa T, Yamada K, et al. Predominance of T lymphocytes in pancreatic islets and spleen of pre-diabetic non-obese diabetic (NOD) mice: a longitudinal study. Clin Exp Immunol, 1985;60(3):622–630.

56. Like AA, Biron CA, Weringer EJ, et al. Prevention of diabetes in BioBreeding/Worcester rats with monoclonal antibodies that recognize T lymphocytes or natural killer cells. The J ExpMed, 1986;164(4):1145–1159.

57. Christianson SW, Shultz LD, Leiter EH. Adoptive transfer of diabetes into immunodeficient NOD-scid/scid mice. Relative contributions of CD4+ and CD8+ T-cells from diabetic versus prediabetic NOD.NON-Thy-1a donors. Diabetes, 1993;42(1):44–55.

58. Groen H, Klatter F, Pater J, et al. Temporary, but essential requirement of CD8+ T cells early in the pathogenesis of diabetes in BB rats as revealed by thymectomy and CD8 depletion. Clin Develop Immunol, 2003;10(2-4):141–151.

59. Wu Q, Salomon B, Chen M, et al. Reversal of spontaneous autoimmune insulitis in nonobese diabetic mice by soluble lymphotoxin receptor. J Exp Med, 2001;193(11):1327–1332.

60. Gommerman JL, Browning JL. Lymphotoxin/light, lymphoid microenvironments and autoimmune disease. Nat Rev Immunol, 2003;3(8):642–655.

61. Valdes AM, Thomson G, Barcellos LF. Genetic variation within the HLA class III influences T1D susceptibility conferred by high-risk HLA haplotypes. Genes Immunity, 2010;11(3):209–218.

62. Luczynski W, Stasiak-Barmuta A, Urban R, et al. Lower percentages of T regulatory cells in children with type 1 diabetes - preliminary report. Ped Endocrinol, Diabetes Metabol, 2009;15(1):34–38.

63. Vrabelova Z, Hrotekova Z, Hladikova Z, et al. CD 127- and FoxP3+ expression on CD25+CD4+ T regulatory cells upon specific diabetogeneic stimulation in high-risk relatives of type 1 diabetes mellitus patients. Scand J Immunol, 2008;67(4):404–410.

64. Link M, Salur L, Kisand K, et al. Higher FoxP3 mRNA expression in peripheral blood mononuclear cells of GAD65 or IA-2 autoantibody-positive compared with autoantibody-negative persons. Apmis, 2008;116(10):896–902.

65. Putnam AL, Brusko TM, Lee MR, et al. Expansion of human regulatory T-cells from patients with type 1 diabetes. Diabetes, 2009;58(3):652–662.

66. Long SA, Walker MR, Rieck M, et al. Functional islet-specific Treg can be generated from CD4+CD25- T cells of healthy and type 1 diabetic subjects. Eur J Immunol, 2009;39(2):612–620.

67. Schneider A, Rieck M, Sanda S, et al. The effector T cells of diabetic subjects are resistant to regulation via CD4+ FOXP3+ regulatory T cells. J Immunol., 2008; 181(10),7350–7355.

68. Ferencik M, Stvrtinova V, Hulin I, Novak M. Inflammation-a lifelong companion. Attempt at a non-analytical holistic view. Folia Microbiol, 2007;52(2):159–173.

69. Luo X, Herold KC, Miller SD. Immunotherapy of type 1 diabetes: where are we and where should we be going? Immunity, 2010;32(4):488–499.

70. Flodstrom M, Maday A, Balakrishna D, et al. Target cell defense prevents the development of diabetes after viral infection. Nature Immunol, 2002;3(4):373–382.

71. Gapin L, Godfrey DI, Rossjohn J. Natural Killer T cell obsession with self-antigens. Curr Opin Immunol, 2013;25(2):168–173.

72. Kukreja A, Costi G, Marker J, et al. NKT cell defects in NOD mice suggest therapeutic opportunities. J Autoimmun, 2002;19(3):117–128.

73. Oikawa Y, Shimada A, Yamada S, et al. High frequency of valpha24(+) vbeta11(+) T-cells observed in type 1 diabetes. Diabetes Care, 2002;25(10):1818–1823.

74. Diana J, Gahzarian L, Simoni Y, Lehuen A. Innate immunity in type 1 diabetes. Discov Med, 2011;11(61):513–520.

75. Serreze DV, Chapman HD, Varnum DS, et al. B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new “speed congenic” stock of NOD.Ig mu null mice. The Journal of experimental medicine, 1996;184(5), 2049–2053.

76. Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, et al. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. New Eng J Med, 2009;361(22):2143–2152.

77. Hu CY, Rodriguez-Pinto D, Du W, et al. Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. J Clin Invest, 2007;117(12):3857–3867.

78. Hinman RM, Cambier JC. Role of B lymphocytes in the pathogenesis of type 1 diabetes. Curr Diab Rep., 2014;14(11):543–550.

79. Koczwara K, Bonifacio E, Ziegler AG. Transmission of maternal islet antibodies and risk of autoimmune diabetes in offspring of mothers with type 1 diabetes. Diabetes, 2004; 53(1):1–4.

80. Towns R, Pietropaolo M. GAD65 autoantibodies and its role as biomarker of Type 1 diabetes and Latent Autoimmune Diabetes in Adults (LADA). Drugs Future, 2011; 36(11):847.

81. Bingley PJ, Gale EA. Progression to type 1 diabetes in islet cell antibody-positive relatives in the European Nicotinamide Diabetes Intervention Trial: the role of additional immune, genetic and metabolic markers of risk. Diabetol, 2006;49(5):881–890.

82. Hummel M, Bonifacio E, Schmid S, et al. Brief communication: early appearance of islet autoantibodies predicts childhood type 1 diabetes in offspring of diabetic parents. Ann Int Med, 2004;140(11):882–886.

83. 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(3):460–468.

84. Kawasaki E. Type 1 Diabetes and Autoimmunity. Clin Pediatr Endocrinol, 2014; 23(4):99–105.

85. Wållberg M, Cooke A. Immune mechanisms in type 1 diabetes. Trends Immunol, 2013;34(12):583–591.

Labels
Hygiene and epidemiology Medical virology Clinical microbiology
Topics Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#