Journal of Endocrinological Investigation

, Volume 6, Issue 5, pp 395–400 | Cite as

Immunology in the early stages of type I diabetes

  • U. Di Mario
  • P. Pozzilli
  • D. Andreani
Review Article


Islet cells antibodies Immune complexes K cells type I diabetes 


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  1. 1.
    Page Faulk W., Karam J.H., Fudenberg H.H. Human anti-insulin antibodies. J. Immunol. 106: 1112, 1971.Google Scholar
  2. 2.
    Jayarao K., Page Faulk W., Karam J.H., Grodsky G.M., Forsham P.H. Evidence in support of the concept of immune complex disease in insulin treated diabetics. In: P.A., Gepts W. (Eds.), Immunity and autoimmunity in diabetes mellitus. Excerpta Medica, Amsterdam, 1974, P. 255.Google Scholar
  3. 3.
    Berns A.W., Owens C.T., Hirata Y., Blumenthal H.T. The pathogenesis of diabetic glomerulosclerosis. II. A demonstration of insulin binding capacity of the various histopathologic components of the disease by fluores cence microscopy. Diabetes 11: 308, 1962.PubMedGoogle Scholar
  4. 4.
    Fallucca F., Iavicoli M., Russo A., Ventriglia L., Melilli S., De Gado F., Padri A., Andreani D. IgG insulin antibodies in the fetus of the diabetic mother. In: Pinchera A., Doniach D., Fenzi G.F., Baschieri L. (Eds.), Autoimmune aspects of endocrine disorders. Academic Press Inc., London, 1980, P. 307.Google Scholar
  5. 5.
    Ortved Andersen O. Anti-insulin antibodies and late diabetic complications. Acta Endocrinol. (-Kbh.) 83: 329, 1976.Google Scholar
  6. 6.
    Bagdade J.D., Root R.K., Bulger R.J. Impaired leukocyte function in patients with poorly controlled diabetes. Diabetes 23: 9, 1974.PubMedGoogle Scholar
  7. 7.
    Irvine W.J. Autoimmunity in endocrine disease. Proc. R. Soc. Med. 67: 548, 1974.PubMedCentralPubMedGoogle Scholar
  8. 8.
    Irvine W.J., Clarke B.F., Scarth L, Cullen D.R. Thyroid and gastric autoimmunity in patients with dia betes mellitus. Lancet 2: 163, 1970.PubMedCrossRefGoogle Scholar
  9. 9.
    Gepts W. Pathologic anatomy of the pancreas in juvenile diabetes. Diabetes 14: 619, 1965.PubMedGoogle Scholar
  10. 10.
    Nerup J., Andersen O.O., Bendixen G., Poulsen J.E., Egeberg J., Gunnerson R., Kromann G. Cell-mediated immunity in diabetes mellitus. Proc. R. Soc. Med. 67: 506, 1974.PubMedCentralPubMedGoogle Scholar
  11. 11.
    MacCuish A.C., Jordan J., Campbell C.J., Duncan L.J.P., Irvine W.J. Cell-mediated immunity to human pancreas in diabetes mellitus. Diabetes 23: 693, 1974.PubMedGoogle Scholar
  12. 12.
    MacCuish A.C., Irvine W.J. Autoimmunological aspects of diabetes mellitus. In: Irvine W.J. (Ed.), Autoimmunity in endocrine disease. Clin. Endocrinol. Metab. 4: 2, 1975.CrossRefGoogle Scholar
  13. 13.
    Bottazzo G.F., Florin-Christensen G., Doniach D. Isletcell antibodies in diabetes mellitus with autoimmune polyendocrine deficiences. Lancet 2: 1279, 1974.PubMedCrossRefGoogle Scholar
  14. 14.
    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 2: 1529, 1974.PubMedCrossRefGoogle Scholar
  15. 15.
    Lendrum R., Walker G.J., Gamble D.R. Islet-cell antibodies in juvenile diabetes mellitus of recent onset. Lancet 1: 880, 1975.PubMedCrossRefGoogle Scholar
  16. 16.
    Irvine W.J., McCallum C.J., Gray R.S., Campbell C.J., Duncan L.J.P., Farquhar J., Vaughan H., Morris P.J. Pancreatic islet cell antibodies in diabetes mellitus correlated withe the duration and type of diabetes coex istent autoimmune disease and HLA type. Diabetes 26: 138, 1977PubMedCrossRefGoogle Scholar
  17. 17.
    Nerup J., Platz P., Andersen O.O., Christy M., Lyngsoe J., Poulsen J.E., Ryder L.P., Staub-Nielsen L., Thomsen M., and Svegaard A. HLA antigens in diabetes mellitus. Lancet 2: 864, 1974.PubMedCrossRefGoogle Scholar
  18. 18.
    Cudworth A.G., Woodrow J.C. Genetic susceptibility in Type I (insulin dependent) diabetes. Diabetologia 12: 382, 1976.Google Scholar
  19. 19.
    Thomsen M., Platz P., Andersen O.O., Christy Y., Lyngsoe J., Nerup J., Rasmussen K., Ryder L.P., Staub-Nielsen L., Sveigaard A. MLC typing in juvenile diabetes mellitus and idiopathic Addison’s disease. Transplantation Review 22: 125, 1975.Google Scholar
  20. 20.
    Morris P.J., Vaughan H., Irvine W.J., McCallum C.J., Gray R.S., Campbell C.J., Duncan L.J.P., Farquhar J.W. HLA and pancreatic islet cell antibodies in diabetes. Lancet 2: 652, 1976.PubMedCrossRefGoogle Scholar
  21. 21.
    Nerup J., Cathelineau C., Seignalet J., Thomsen M. HLA and endocrine disease. In: Dausset J., Sveigaard A. (Eds.), HLA and disease. Munksgaard, Copenhagen, 1977, P. 308.Google Scholar
  22. 22.
    Cudworth A.G. Types of diabetes and its pathogenesis. In: Randle P., Steiner D., Whelan W.G. (Eds.), Carbohydrate metabolism and its disorder. Academic Press, London, 1980, P. 91.Google Scholar
  23. 23.
    Pyke D.A., Nelson P.G. Diabetes in identical twins. In: Creutzfeldt W., Kobberling J., Neel J.V. (Eds.), The genetics of diabetes mellitus. Springer Verlag, Berlin, Heidelberg and New York, 1978, P. 194.Google Scholar
  24. 24.
    Bertrams J., Jansen F.K., Gruneklee D., Reis H.E., Drost H., Beyer J., Gries F.A., Kuwert E. HLA antigens and immunoresponsivenesses to insulin in insulin dependent diabetes mellitus. Tissue Antigens 8: 13, 1976.PubMedCrossRefGoogle Scholar
  25. 25.
    Irvine W.J., Di Mario U., Feek C.M., Ting A., Morris P.J., Gray R.S., Duncan L.J.P. Insulin antibodies in relation to islet cell antibodies and HLA Antigens in insulin-dependent (type I) diabetes. J. Clin. Lab. Immunol. 1: 111, 1978.Google Scholar
  26. 26.
    Gundersen E. Is diabetes of infectious origin? J. Infect. Dis. 41: 197, 1927.CrossRefGoogle Scholar
  27. 27.
    Cahill G.F., McDevitt H.O. Insulin dependent diabetes mellitus: the initial lesion. N. Eng. J. Med. 305: 1454, 1981.CrossRefGoogle Scholar
  28. 28.
    Cudworth A.G., Gamble D.R., White G.B.B., Lendrum R., Woodrow J.C., Bloom A. Etiology of diabetes: a prospective study. Lancet 1: 385, 1977.PubMedCrossRefGoogle Scholar
  29. 29.
    Gamble D.R. Viruses and diabetes: an overview with special reference to epidemiological studies. In: Bajaj J.S. (Ed.), Diabetes Excerpta Medica, Amsterdam, 1977, P. 285.Google Scholar
  30. 30.
    Craighead J.E. Viral diabetes in man and experimental animals. Am. J. Med. 70: 127, 1981.PubMedCrossRefGoogle Scholar
  31. 31.
    Notkins A. The causes of diabetes. Sci. Am. 241: 62, 1979.PubMedCrossRefGoogle Scholar
  32. 32.
    Appel M.C., Rossini A.A., Williams R.M., Like A.A. Viral studies in streptozotocin-induced pancreatic insulitis. Diabetologia 15: 327, 1978.PubMedCrossRefGoogle Scholar
  33. 33.
    Irvine W.J., Di Mario U., Guy K., Borsey D.Q. Immune complexes in Type I diabetes mellitus with and without persistent islet cell antibody. J. Clin. Lab. Immunol. 4: 87, 1980.PubMedGoogle Scholar
  34. 34.
    Irvine W.J., McCallum C.J., Gray R.S., Duncan L.J.P. Clinical and pathogenic significance of pancreatic islet cell antibodies in diabetics treated with oral hypoglycaemic agents. Lancet 1: 1025, 1977.PubMedCrossRefGoogle Scholar
  35. 35.
    Irvine W.J., Sawers J.S.A., Feek C.M., Prescott R.J., Duncan L.J.P. The value of islet cell antibody in predicting secondary failure of oral hypoglycaemic agent therapy in diabetes mellitus. J. Clin. Lab. Immunol. 2: 23, 1979.PubMedGoogle Scholar
  36. 36.
    Gorsuch A.N., Lister J., Dean B.M., Spencer K.M., McNally J.M., Bottazzo G.F., Cudworth A.G. Evidence for a long prediabetic period in type I (insulin dependent) diabetes mellitus. Lancet 2: 1363, 1981.PubMedCrossRefGoogle Scholar
  37. 37.
    Irvine W.J. Classification of idiopathic diabetes. Lancet 1: 638–42, 1977.PubMedCrossRefGoogle Scholar
  38. 38.
    National Diabetes Data Group, Classification of Diabetes Mellitus. Diabetes 28: 1039, 1979.CrossRefGoogle Scholar
  39. 39.
    Bottazzo G.F., Puyol Borrel R., Doniach D. Humoral and cellular immunity in diabetes mellitus. In: Holborow E.J. (Ed.), Clinics in immunology and allergy. Saunders, London, 1981, P. 139.Google Scholar
  40. 40.
    Di Mario U., Irvine W.J., Borsey D.Q., Kyner J.L., Weston J., Galfo C., Immune abnormalities in diabetic patients not requiring insulin at diagnosis. Diabetologia 25: 392, 1983.PubMedCrossRefGoogle Scholar
  41. 41.
    Lernmark A., Freedman Z.R., Hofmann C., Rubenstein A.H., Steiner D.F., Jackson R.L., Winter R.J., Traisman H.S. Islet-cell-surface antibodies in juvenile diabetes mellitus. N. Engl. J. Med. 299: 175, 1978.CrossRefGoogle Scholar
  42. 42.
    Lernmark A., Kanatsuna T., Patzelt C. Antibodies directed against the pancreatic islet-cell plasma membrane: detection and specificity. Diabetologia, 445, 1980.Google Scholar
  43. 43.
    Dobersen M.J., Scarff J.E., Ginsberg-Fellner F., Notkins A.L. Cytotoxic autoantibodies to beta cells in the serum of patients with insulin-dependent diabetes mellitus. N. Engl. J. Med. 303: 1493, 1980.PubMedCrossRefGoogle Scholar
  44. 44.
    Soderstrom W/K., Freedman Z., Lenmark A. Complement dependent cytotoxic islet-cell surface an tibodies in insulin-dependent diabetes. Diabetes 28: 397, 1979.Google Scholar
  45. 45.
    Rittenhouse H.G., Oxender D.L., Pek S.A.D. Coplement-mediated cytotoxic effect on pancreatic islet with sera from diabetic patients. Diabetes 29: 317–22, 1980.PubMedCrossRefGoogle Scholar
  46. 46.
    Eisenbarth G.S., Morris M.A., Scearce R.M. Cytotoxic antibodies to cloned rad islet-cells in serum of patients with diabetes mellitus. J. Clin. Invest. 67: 403, 1981.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Irvine W.J., Di Mario U., Guy K., Peek C.M., Gray R.S., Duncan L.J.P. Immune complexes in newly diagnosed insulin dependent type I diabetics. J. Clin. Lab. Immunol. 1: 183, 1978.PubMedGoogle Scholar
  48. 48.
    Borsey D.Q., Di Mario U., Irvine W.J., Gray R.S. Weston J., Bendherer J., Duncan L.J.P. Humoral immunity in type I diabetes mellitus: a prospective study. J. Clin. Lab. Immunol. 11: 9, 1983.PubMedGoogle Scholar
  49. 49.
    Sensi M., Pozzilli P. Cell-mediated immunity in families of Type I diabetic patients. In: Waldhaust W., Alberti K.G.M.M. (Eds.), Diabetes 1979. Excerpta Medica, Amsterdam, 1979, P. 211.Google Scholar
  50. 50.
    West W.H., Payne S.M., Weese J.L., Herberman R.B. Human T Lymphocyte subpopuiations: correlation be tween E-rosette forming affinity and expression of Fc receptor. J. Immunol. 119: 548, 1977.PubMedGoogle Scholar
  51. 51.
    Robbins D.S., Donnan G.G., Fudenberg H.H., Strelkaus- kas A.J. Functional subsets of human T cells defined by “active” rosette formation. Cell. Immunol. 59: 205, 1981.PubMedCrossRefGoogle Scholar
  52. 52.
    West W.H., Boozer R.B., Herberman R.B. Low affinity E-rosette formation by the human K cell. J. Immunol. 120: 90, 1980.Google Scholar
  53. 53.
    Pozzilli P., Sensi M., Dean B., Goruch A.N., Cudworth A.G. The importance of measuring Fc + (Killer) cells in insulin-dependent (Type I) diabetes. Acta Diabetol. Lab. 17: 119, 1980.CrossRefGoogle Scholar
  54. 54.
    Pozzilli P., Sensi M., Gorsuch A.N., Bottazzo G.F., Cudworth A.G. Evidence for raised K cell levels in Type I diabetes. Lancet 2: 173, 1979.PubMedCrossRefGoogle Scholar
  55. 55.
    Sensi M., Pozzilli P., Gorsuch A.N., Bottazzo G.F., Cudworth A.G. Increased killer cell activity in insulin dependent (Type I) diabetes. Diabetologia 20: 106, 1981.PubMedCrossRefGoogle Scholar
  56. 56.
    Bottazzo G.F., Mann J.I., Thorogood M., Baum J.D., Doniach D. Autoimmunity in diabetics and their families. Br. Med. J. 2: 165, 1978.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Boitard C., Debray-Sachs, Pouplard A., Assan R. Inhibition of insulin release by lymphocytes from diabet ic patients in vitro. Diabetologia 19: 259, 1980.Google Scholar
  58. 58.
    Buschard K., Madsbad S., Rygaard J. Depresses suppressor cell activity in patients with newly diagnosed insulin dependent diabetes mellitus. Clin. Exp. Immunol. 41: 25, 1980.PubMedCentralPubMedGoogle Scholar
  59. 59.
    Galluzzo A., Giordano C., Sparacino C., Bompiani G.D. Studies on suppressor cell function in recent-onset juvenile diabetes. Diabetologia 19: 275, 1980.Google Scholar
  60. 60.
    Pozzilli P., Di Mario U., Iavicoli M., Menzinger G., Andreani D. Inhibition of allogeneic lymphocyte E-rosettes induced by sera from newly diagnosed type I diabetics. Acta Endocrinol. (Kbh.) 93: 49, 1980.Google Scholar
  61. 61.
    Mirakian R., Cudworth A.G., Bottazzo G.F. Autoimmunity to anterior pituitary cells as a possible pathogenetic factor in the preclinical stage of type la juvenile insulin dependent diabetes. Diabetes (Suppl.) 2: 48A, 1982.Google Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 1983

Authors and Affiliations

  • U. Di Mario
    • 1
  • P. Pozzilli
    • 1
  • D. Andreani
    • 1
  1. 1.Cattedra di Endocrinologia IUniversita di Roma, Clinica Medica 2RomaItaly

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