Medical Hypotheses
Volume 57, Issue 5 , Pages 532-538 , November 2001

Vaccines and the risk of insulin-dependent diabetes (IDDM): potential mechanism of action

  • J.B. Classen

      Affiliations

    • Classen Immunotherapies Inc. Baltimore, Maryland, USA
    • ,
  • D.C. Classen

      Affiliations

    • Division of Infectious Diseases, LDS Hospital and University of Utah School of Medicine, Salt Lake City, Utah, USA

Received 28 July 2000 ,Accepted 23 January 2001.

References 

  1. Classen DC, Classen JB. The timing of pediatric immunization and the risk of insulin-dependent diabetes mellitus. Infect Dis Clini Pract. 1997;6:449–454
  2. Classen JB, Classen DC. Association between type 1 diabetes and Hib vaccine, causal relation likely. BMJ. 1999;319:1133
  3. Classen JB, Classen DC. Immunisation and type 1 diabetes mellitus: is there a link?. Drug Safety. 1999;21:423–425
  4. Maclaren N. Immunology of diabetes mellitus. Ann Allergy. 1992;68:5–9
  5. Classen JB. The timing of immunization affects the development of diabetes in rodents. Autoimmunity. 1996;24:137–145
  6. Classen JB, Classen DC. Immunization in the first month of life may explain decline in incidence of IDDM in the Netherlands. Autoimmunity. 1999;31:43–45
  7. Hemachuda T, Griffin DE, Giffels JJ, Johnson RT, Moser AB, Phanuphak P. Myelin basic protein as an encephalomyelitis and polyneuritis following rabies vaccination. N Engl J Med. 1987;316:369–374
  8. Giudice GD, Gervaix A, Costantino P, Costantino P. Priming to heat shock proteins in infants vaccinated against pertussis. J Immunol. 1993;150:2025–2032
  9. Elias D, Markovitis D, Reshef T, van der Zee R, Cohen IR. Induction and therapy of autoimmune diabetes in the non-obese diabetic (NOD/Lt) mouse by a 65-kDa heat shock protein. Proc Natl Acad Sci USA. 1990;87:1576–1580
  10. Meiselas LE, Zingale SB, Lee SL, Richman S, Siegel M. Antibody production in rheumatic diseases, the effect of Brucella antigen. J Clin Invest. 1961;40:1872–1881
  11. Huang YP, Gauthey L, Michel M, Michel M. The relationship between vaccine-induced antibody responses and vaccine induced nonspecific autoantibody responses in healthy older women. J Gerontol. 1992;47:50–55
  12. Hackett E, Beech M. Transient appearance of autoimmune antibodies during prophylactic immunization. J Immunol. 1960;85:533–538
  13. Caspary EA, Field EJ, Ball J. Antibody studies in multiple sclerosis and experimental allergic encephalitis. J Neurol Neurosurg Psych. 1964;27:25–28
  14. Waguri M, Hanafusa T, Itoh N, Itoh N. Occurrence of IDDM during interferon therapy for chronic viral. Diabetes Res Clin Pract. 1994;23:33–36
  15. Murakami M, Iriuchijima T, Mori M. Diabetes and Interferon-alpha therapy. Ann Intern Med. 1995;123:318
  16. Fabris P, Betterle C, Floreani A, Floreani A. Development of type 1 diabetes mellitus during interferon alpha therapy for chronic HCV hepatitis. Lancet. 1992;340:548
  17. Imagawa A, Itoh N, Hanafusa T, Waguri M, Kuwajima M, Matsuzawa Y. Antibodies to glutamic acid decarboxylase induced by interferon-alpha therapy for chronic hepatitis. Diabetologia. 1996;39:126
  18. Fattovich G, Giustina G, Favarto S, Ruol A. A survey of adverse events in 11,241 patients with chronic viral hepatitis treated with alpha interferon. J Hepatol. 1996;24:38–47
  19. Rabinovitch A. An update on cytokines in the pathogenesis of insulin-dependent diabetes mellitus. Diabetes Metab Res Rev. 1998;14:129–151
  20. Minagawa H, Kobayashi H, Yoshida H, Yoshida H. Intratumoral induction of tumor necrosis factor by systemic administration of Bordetella pertussis vaccine. Br J Cancer. 1990;62:372–375
  21. Yosihiro N, Parant M, Parant F, Chedid L. Production of tumor necrosis factor in nude mice by muramyl peptides associated with bacterial vaccines. Cancer Res. 1988;48:5766–5769
  22. Schwartzentruber DJ, White DE, Zweig MH, Weintraub BD, Rosenberg SA. Thyroid dysfunction associated with immunotherapy for patients with cancer. Cancer. 1991;68:2384–2390
  23. Conlon KC, Urba WJ, Smith JW, Steis RG, Longo DL, Clark JW. Exacerbation of symptoms of autoimmune disease in patients receiving alpha-interferon therapy. Cancer. 1990;65:2237–2242
  24. Burman P, Totterman TH, Oberg K, Karlsson FA. Thyroid autoimmunity in patients on long term therapy with leukocyte derived interferon. J Clini Endocrinol Metab. 1986;63:1086–1090
  25. Panitch HS, Haley AS, Hirsch RL, Johnson KP. Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet. 1987;18:893–894
  26. Dahlquist G, Kallen B. Maternal-child blood group incompatibility and other perinatal events increase the risk for early -onset Type 1 (Insulin-dependant) diabetes mellitus. Diabetologia. 1992;35:671–675
  27. Zielasek J, Burkart V, Naylor P, Goldstein A, Kiesel U, Kolb H. Interleukin-2-dependant control of disease development in spontaneously diabetic BB Rats. Immunology. 1990;69:209–214
  28. Kolb H, Zielasek J, Treichel U, Freytag G, Wrann M, Kiesel U. Recombinant interleukin 2 enhances spontaneous insulin dependent diabetes in BB rats. Eur J Immunol. 1986;16:209–212
  29. Bendtzen K, Mandrup-Poulsen T, Nerup J, Nielsen JH, Dinarello CA, Svenson M. Cytotoxicity of human p17 interleukin-1 for pancreatic islets of Langerhans. Science. 1986;232:1545–1547
  30. Mandrup-Poulsen T, Bendtzen K, Dinnarello CA, Nerup J. Human TNF potentiates human IL-1 mediated pancreatic B cell cytotoxicity. J Immunol. 1987;139:4077–4082
  31. Picarella DE, Kratz A, Chang-ben L, Ruddle NH, Flavell RA. Transgenic tumor necrosis factor (TNF) alpha, production in islet cells leads to insulitis, not diabetes. J Immunol. 1993;150:4136–4150
  32. Campbell IL, Kay TWH, Oxbrow L, Harrison LC. Essential role for interferon gamma and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice. J Clin Invest. 1991;87:739–742
  33. Pujol-Borrell R, Todd I, Doshi M, Doshi M. HLA class II induction in human islet cells by interferon gamma plus tumor necrosis factor or lymphotoxin. Nature. 1987;326:304–306
  34. von Herrath MG, Allison J, Miller JFAP, Oldstone MBA. Focal expression of interleukin 2 does not break unresponsiveness to self (viral) antigen expressed in beta cells but enhances development of autoimmune disease (diabetes) after initiation of an anti-self immune response. J Clin Invest. 1995;95:477–485
  35. Jacob CO, Aiso S, Michie SA, McDevitt HO, Acha-Orbea H. Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF): similarities between TNF-alpha and interleukin 1. Proc Natl Acad Sci USA. 1990;87:968–972
  36. Formby B, Jacobs C, Dubuc P, Shao T. Exogenous administration of IL-1 alpha inhibits active and adoptive transfer autoimmune diabetes in mice. Autoimmunity. 1992;12:21–27
  37. Serreze DV, Hamaguchi K, Leiter EH. Immunostimulation circumvents diabetes in NOD/Lt mice. J Autoimmun. 1989;2:759–776
  38. Wilson CA, Jacobs C, Baker P, Baker P. IL-1 beta modulation of spontaneous autoimmune diabetes and thyroiditis in the BB Rat. J Immunol. 1990;144:3784–3788
  39. Satoh J, Seino H, Shintani S, Shintani S. Inhibition of Type 1 diabetes in BB rats with recombinant human tumor necrosis factor-alpha. J Immunol. 1990;145:1395–1399
  40. Rabinovitch A. Immunoregulatory and cytokine imbalances in the pathogenesis of IDDM. Diabetes. 1994;43:613–621
  41. Kolb H. Benign versus destructive insulitis. Diabetes Metab Res Rev. 1997;13:139–146
  42. Delovitch TL, Singh B. The nonobese diabetic mouse as a model of autoimmune diabetes: immune dysregulation gets the NOD. Immunity. 1997;7:727–738
  43. Hussain MJ, Maher J, Warnock T, Vats A, Peakman M, Vergani D. Cytokine overproduction in healthy first degree relatives of patients with IDDM. Diabetologia. 1998;41:343–349
  44. Szelachowska M, Kretowski A, Kinalska I. Increased in vitro interleukin-12 production by peripheral blood in high-risk IDDM first degree relatives. Horm Metab Res. 1997;29:168–171
  45. Kolb-Bachofen V, Kolb H. A role for macrophages in the pathogenesis of type 1 diabetes. Autoimmunity. 1989;3:145–163
  46. Mannhalter JW, Neychev HO, Zlabinger GJ, Ahmad R, Eibl MM. Modulation of the human immune response by non-toxic and non-pyrogenic adjuvant aluminum hydroxide: effect on antigen uptake and antigen presentation. Clin Exp Immunol. 1985;61:143–151
  47. Artursson P, Edman P, Ericsson JL. Macrophage stimulation with some structurally related polysaccharides. Scand J Immunol. 1987;25:245–254
  48. Murphy C, Newsholme PT. The role played by immunostimulated macrophages in the pathogenesis of insulin dependent diabetes mellitus. Biochem Soc Trans. 1997;25:368S
  49. Yoon JW, Jun HS, Santamaria P. Cellular and molecular mechanisms for the initiation and progression of beta cell destruction resulting from the collaboration between macrophages and T cells. Autoimmunity. 1998;27:109–122
  50. Rothe H, Kolb H. The APC1 concept of type I diabetes. Autoimmunity. 1998;27:179–184
  51. Katsh S. Adjuvants and aspermatogenesis in guinea pigs. Intl Arch Allergy. 1964;24:319–331
  52. Levine S, Wenk EJ. Hyperacute allergic encephalomyelitis, lymphatic system as site of adjuvant effect of pertussis vaccine. Am J Pathol. 1967;50:465–481
  53. Gearing AJH, Bird C, Wadha M, Redhead K. The primary and secondary cellular immune responses to whole cell Bordetella pertussis vaccine and its components. Clin Exp Immunol. 1987;68:275–281
  54. Tvede N, Heilmann C, Christensen D. Interleukin 2 receptor expression by human blood lymphocytes after vaccination with pneumococcal polysaccharides. Clin Exp Immunol. 1989;76:404–411
  55. Griffin PD. Immunization against HCG. Hum Reprod. 1994;9:267–272
  56. Schutze MP, LeClerc C, Jolivet M, Jolivet M. A potential anti-pregnancy vaccine built by conjugation of the B-subunit of human chorionic gonadotropin to adjuvant-active muramyl peptide. Am J Reprodu Immunolo. 1987;14:84–90
  57. Anonymous. Aphton Corporation, Annual Report.
  58. Mancini RE. Allergic aspermatogeneisis experimentally induced in men and animals. In:  Thomas L,  Uhr JW,  Grant L editor. International Symposium on Injury, Inflammation and Immunity. Stoke Pages; 1962;p. 365–387
  59. Gerfo PL, Feind C, Weber C, Ting W. Immunotherapy of cancer by the induction of autoimmunity. Surgery. 1983;94:959–965
  60. Hjorth RN, Bonde GM, Piner E, Hartzell RW, Rorke LB, Rubin BA. Experimental neuritis induced by a mixture of neural antigens and influenza vaccines. J Neuroimmunol. 1984;6:1–8
  61. Greiner DL, Mordes JP, Handler ES, Angelillo M, Nakamura N, Rossini AA. Depletion of RT6.1 positive lymphocytes induces diabetes in resistant Biobreeding/Worchester (BB/W) rats. J Exp Med. 1987;166:461–475
  62. Levine S, Wenk EJ. Exacerbation and transformation of allergic encephalomyelitis by the pertussis vaccine. PSEBM. 1966;112:115–118
  63. Aho K, Konttinen A, Rajasalmi M, Wager O. Transient appearance of rheumatoid factor in connection with prophylactic vaccinations. Acta Pathol Microbial Scand. 1962;56:478–479
  64. Aho K, Somer T, Salo OP. Rheumatoid factor and immuno–conglutinin response following various vaccinations. PSEBM. 1967;124:229–233
  65. Palit J, Chattopadhyay C, Malaviya AN, Uberoi S, Kumar R. Some immunological parameters in rheumatoid arthritis from India. Biomedicine. 1977;27:70–73
  66. Welch MJ, Fong S, Vaughan J, Carson D. Increased frequency of rheumatoid factor precursor B lymphocytes after immunization of normal adults with tetanus toxoid. Clin Exp Immunol. 1982;51:299–304
  67. Lewis K, Jordan SC, Cherry JD, Sakai RS, Le CT. Petechiae and urticaria after DTP vaccination, detection of circulating immune complexes containing vaccine-specific antigens. J Pediatrics. 1986;109:1009–1012
  68. Haneberg B, Matre R, Winsnes R, Dalen A, Vogt H, Fine PH. Acute hemolytic anemia related to diphtheria-pertussis-tetanus vaccination. Acta Paedia Scand. 1978;67:345–350
  69. Brown RC, Blecher TE, French EA, Toghill PJ. Thrombotic thrombocytopenic purpura after influenza vaccination. BMJ. 1973;i:303
  70. Zupanska B, Lawkowicz W, Gorska B, Gorska B. Autoimmune haemolytic anemia in children. B J Haematol. 1976;34:511–520
  71. Kelton JG. Vaccination-associated relapse in immune thrombocytopenia. J Am Med Assoc. 1981;245:369–371
  72. Klemparskaya N. Autohaemolysis-producing cells in mice injected with bacterial vaccines. Immunology. 1973;25:11–15
  73. Amsel SG, Hanukoglu A, Fried D, Wolyvovics M. Myocarditis after triple immunisation. Arch Dis Childhood. 1986;61:403–405
  74. Helle EPJ, Koskenvuo K, Heikkila J, Pikkarainen J, Weckstrom P. Myocardial complications of immunisation. Ann Clin Res. 1978;10:280–287
  75. Rose NR, Herskowitz A, Neumann DA, Neu N. Autoimmune myocarditis. Immunol Today. 1988;9:117–120
  76. Landian-Olsson M, Karlsson A, Dahlquist G, Dahlquist G. Islet cell and other organ-specific autoantibodies in all children developing type 1 (insulin-dependent) diabetes mellitus in Sweden during one year and in matched control children. Diabetologia. 1989;32:387–395
  77. Groop LC, Bottazzo GF, Doniach D. Islet cell antibodies identify latent type I diabetes in patients aged 35–75 years at diagnosis. Diabetes. 1986;35:237–241
  78. Niskanen L, Karjalainen J, Sarlund H, Sittonen O, Uusitupa M. Five-year follow-up of islet cell antibodies in Type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 1991;34:402–408
  79. Schenker M, Hummel M, Ferber K, Ferber K. Early expression and high prevalence of islet autoantibodies for DR3/4 heterozygous and DR4/4 homozygous offspring of parents with type I diabetes: the German BABYDIAB study. Diabetologia. 1999;42:671–677
  80. Zeigler AG, Hummel M, Schenker M, Bonifacio E. Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type I diabetes: the 2 year analysis of the German BABYDIAB study. Diabetes. 1999;48:460–468
  81. Kulmala P, Rahko J, Savola K, Savola K. Stability of autoantibodies and their relation to genetic and metabolic markers of Type I diabetes in initially unaffected schoolchildren. Diabetologia. 2000;43:457–464
  82. Bodansky HJ, Dean BM, Grant PJ, Grant PJ. Does exposure to the rubella virus generate endocrine autoimmunity. Diabetic Medicine. 1990;7:611–614
  83. Sinaniotis CA, Daskalopoulou E, Lapatsanis P, Doxiadis S. Diabetes mellitus after mumps vaccination. Arch Dis Childhood. 1975;50:749
  84. Fescharek R, Quast U, Maass G, Merkle W, Schwarz SM. II Tolerability and analysis of spontaneously reported side effects. Vaccine. 1990;8:446–456
  85. Ginspberg-Fellner F, Witt ME, Yagihashi S, Yagihashi S. Congenital rubella syndrome as a model for type 1 (insulin dependent) diabetes mellitus: increased prevalence of islet cell surface antibodies. Diabetologia. 1984;27:87–89
  86. Numazaki K, Goldman HY, Wong I, Wainberg MA. Infection of cultured human fetal pancreatic cells by rubella virus. Am J Clin Pathol. 1989;91:446–451
  87. Hyoty H, Leinikki P, Reunanen A. Mumps infections in the etiology of type 1 (insulin-dependent) diabetes. Diabetes Res. 1988;9:111–116
  88. Stanley SK, Ostrowski MA, Justement JS, Gantt K, Hedayati S, Mannix M. Effect of immunization with a common recall antigen on viral expression in patients infected with human immunodeficiency virus type I. N Engl J Med. 1996;334:1222–1230
  89. Cheeseman S, Davaro RE, Ellison RT. Hepatitis B Vaccination and Plasma HIV-1 RNA. N Engl J Med. 1996;334:9
  90. Ostrowski MA, Stanley SK, Justement JS, Gantt K, Goletti D, Fauci AS. Increased in vitro tetanus-induced production of HIV type 1 following in vivo immunization of HIV type 1-infected individuals with tetanus toxoid. AIDS Res Hum Retroviruses. 1997;13:473–480
  91. Laron Z, Shamis I, Nitzan-Kaluski D, Ashkenazi I. Month of birth and subsequent development of type 1 diabetes (IDDM). J Pediat Endocrinol Metab. 1999;12:397–402
  92. Dahlquist G, Frisk G, Svanberg L, Forsgren L, Didherolom H. Indications that maternal Coxsackie B virus infection during pregnancy is a risk factor for childhood-onset IDDM. Diabetologia. 1995;38:1371–1373
  93. Hyoty H, Hiltunen M, Knip M. A prospective study on the role of Coxsackie B and other enterovirus infections in the pathogenesis of IDDM. Diabetes. 1995;44:652–657
  94. Dahlquist GG, Boman JE, Juto P. Enteroviral RNA and IgM antibodies in early pregnancy and risk for childhood-onset IDDM in offspring. Diabetes Care. 1999;22:364
  95. Conrad B, Weissmahr RN, Boni J, Arcari R, Schupbach J, Mach B. A human endogenous retroviral superantigen as a candidate autoimmune gene in type I diabetes. Cell. 1997;90:303–313
  96. Patterson CC. Infections and vaccination as risk factors for childhood type I diabetes mellitus: a multicenter case-control investigation. Diabetologia. 2000;43:47–53
  97. Ammann AJ. T cell and T-B cell immunodeficiency disorders. Pediat Clini Nrth Am. 1977;24:293–311
  98. Stewart SR, Gershwin ME. The associations and relationships of congenital immune deficiency states and autoimmune phenomena. Semin Arthr Rheum. 1979;9:98–123
  99. Leon ME, Ward B, Kanashiro R. Immunologic parameters 2 years after high-titre measles immunization in Peruvian children. J Infect Dis. 1993;168:1097–1104
  100. Shaheen SO. Changing patterns of childhood infection and the rise of allergic diseases. Clin Exp Allergy. 1995;25:1034–1037
  101. Kolb H, Elliott RB. Increasing incidence of IDDM a consequence of improved hygene. Diabetologia. 1994;37:729
  102. Ohsugi T, Kurosawa T. Increased incidence of diabetes mellitus in specific pathogen-eliminated offspring produced by embryo transfer in NOD mice with low incidence of the disease. Lab Anim Sci. 1994;44:386–388
  103. Classen JB, Classen DC. Vertically transmitted enteroviruses and the benefits of neonatal immunization. Diabetes Care. 1999;22:1760
  104. Rocken M, Urban JF, Shevach EM. Infection breaks T-cell tolerance. Nature. 1992;359:79–82
  105. Takasu N, Komiya I, Nagasawa Y, Asawa T, Yamada T. Exacerbation of autoimmune thyroid dysfunction after unilateral adrenalectomy in patients with Cushing's syndrome due to an adrenocortical adenoma. NEJM. 1960;1990:1708–1712
  106. Levine S, Sowinski R. The role of the adrenal in relapses of experimental allergic encephalomyelitis. PSEBM. 1975;149:1032–1035

PII: S0306-9877(01)91352-0

doi: 10.1054/mehy.2001.1352

Medical Hypotheses
Volume 57, Issue 5 , Pages 532-538 , November 2001

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