Skip to main content

Advertisement

SpringerLink
Log in

Autoimmune reaction after anti-tetanus vaccination—description of four cases and review of the literature

  • Environment and Autoimmunity
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Autoimmune reaction after vaccination is sporadically reported in the medical literature. Vaccinations are generally safe and have an important role in eradicating endemic diseases worldwide. Nevertheless, the question arises as to whether there is a possibility of post-vaccination autoimmune phenomena. The anti-tetanus vaccine is being used since 1924, and it is part of the recommended immunization schedules for children. There are few reports of autoimmune diseases, such as rheumatoid arthritis and anti-phospholipid syndrome after anti-tetanus vaccination. Herein, we describe four cases, of which we believe, show a clear temporal relation between anti-tetanus vaccination and the appearance of dermatomyositis, systemic lupus erythematosus, type 1 diabetes mellitus and anti-phospholipid syndrome. We also suggest some of the pathogenic mechanisms that promote a pathogenic autoimmune response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Shoenfeld Y, Agmon-Levin N, Tomljenovic L. Vaccines and autoimmunity. Vancouver: Wiley-Blackwell; 2015.

    Book  Google Scholar 

  2. Hua C, Morel J, Ardouin E, Ricard E, Foret J, Mathieu S, et al. Reasons for non-vaccination in French rheumatoid arthritis and spondyloarthritis patients. Rheumatology (Oxford). 2015;54(4):748–50.

    Article  Google Scholar 

  3. Salami S, D’Amelio R. Could autoimmunity be induced by vaccination? Int Rev Immunol. 2010;29(3):247–69.

    Article  Google Scholar 

  4. Benoist C, Mathis D. Autoimmunity provoked by infections; how good is the case for T cell epitope mimicry? Nat Immunol. 2001;2(9):797–801.

    Article  CAS  PubMed  Google Scholar 

  5. Wraith DC. Vaccination an autoimmune diseases: what is the evidence? Lancet. 2003;362(9396):1659–66.

    Article  CAS  PubMed  Google Scholar 

  6. Fujinami RS, von Herrath MG, Christen U, Whitton JL. Molecular mimicry, by-stander activation or viral persistence: infections and autoimmune disease. Clin Microbiol Rev. 2006;19(1):80–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Shoenfeld Y, Agmon-Levin N. ASIA autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011;36(1):4–8.

    Article  CAS  PubMed  Google Scholar 

  8. Perricone C, Colafrancesco S, Mazor RD, Soriano A, Agmon-Levin N, Shoenfeld Y. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: unveiling the pathogenic, clinical and diagnostic aspects. J Autoimmun. 2013;47:1–16.

    Article  CAS  PubMed  Google Scholar 

  9. Petrovsky N, Aguilar JC. Vaccine adjuvants: current state and future trends. Immunol Cell Biol. 2004;82(5):488–96.

    Article  CAS  PubMed  Google Scholar 

  10. Miller E, Waight P, Farrington CP, Andrews N, Stowe J, Taylor B. Idiopathic thrombocytopenic purpura and MMR vaccine. Arch Dis Child. 2001;84(3):227–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Beeler J, Varricchio F, Wise R. Thrombocytopenia after immunization with measles vaccines: review of the vaccine adverse events reporting system (1990–1994). Pediatr Infect Dis J. 1996;15(1):88–90.

    Article  CAS  PubMed  Google Scholar 

  12. Nieminen U, Peltola H, Syrjälä MT, Mäkipernaa A, Kekomäki R. Acute thrombocytopenic purpura following measles, mumps and rubella vaccination. Acta Paediatr. 1993;82:267–70.

    Article  CAS  PubMed  Google Scholar 

  13. Jonville-Béra AP, Autret E, Galy-Eyraud C, Hessel L. Thrombocytopenic purpura after measles, mumps and rubella vaccination: a retrospective survey by the French regional pharmacovigilance centres and pasteur-mérieux sérums et vaccins. Pediatr Infect Dis J. 1996;15(1):44–8.

    Article  PubMed  Google Scholar 

  14. Cines DB, Liebman H, Stasi R. Pathobiology of secondary immune thrombocytopenia. Semin Hematol. 2009;46:S2–14.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Marks JS, Halpin TJ. Guillain–Barré syndrome in recipients of A/New Jersey influenza vaccine. JAMA. 1980;243(24):2490–4.

    Article  CAS  PubMed  Google Scholar 

  16. Langmuir AD. Guillain–Barré syndrome: the swine influenza virus vaccine incident in the United States of America, 1976–77: preliminary communication. J R Soc Med. 1979;72(9):660–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Eisen DP, McBryde ES. Avoiding Guillain–Barré syndrome following swine origin pandemic H1N1 2009 influenza vaccination. J Infect Dis. 2009;200(10):1627–8.

    Article  PubMed  Google Scholar 

  18. Lasky T, Terracciano GJ, Magder L, Koski CL, Ballesteros M, Mash D, et al. The Guillain–Barré syndrome and the 1992–1993 and 1993–1994 influenza vaccines. N Engl J Med. 1998;339:1797–802.

    Article  CAS  PubMed  Google Scholar 

  19. Juurlink DN, Stukel TA, Kwong J, Kopp A, McGeer A, Upshur RE, et al. Guillain–Barré syndrome after influenza vaccination in adults: a population-based study. Arch Intern Med. 2006;166(20):2217–21.

    Article  PubMed  Google Scholar 

  20. Hassan W, Oldham R. Reiter’s syndrome and reactive arthritis in health care workers after vaccination. BMJ. 1994;309(6947):94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Aksu K, Keser G, Doganavsargil E. Reactive arthritis following tetanus and rabies vaccinations. Rheumatol Int. 2006;27(2):209–10.

    Article  PubMed  Google Scholar 

  22. Agmon-Levin N, Zafrir Y, Paz Z. Ten cases of systemic lupus erythematosus related to hepatitis B vaccine. Lupus. 2009;18(13):1192–7.

    Article  CAS  PubMed  Google Scholar 

  23. Centers for Disease Control and Prevention (CDC). Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine from advisory committee on immunization practice. MMWR Morb Mortal Wkly Rep. 2011;60(1):13–5.

    Google Scholar 

  24. Meir A, Rotman-Pikielny P, Levy Y. Antiphospholipid syndrome following a diphtheria-tetanus vaccination: coincidence vs. causality. Isr Med Assoc J. 2010;12(10):638–9.

    Google Scholar 

  25. Zafrir Y, Agmon-Levin N, Paz Z, Shilton T, Shoenfeld Y. Autoimmunity following Hepatitis B vaccine as part of the spectrum of ‘Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants’ (ASIA): analysis of 93 cases. Lupus. 2012;21(2):146–52.

    Article  CAS  PubMed  Google Scholar 

  26. Cerpa-Cruz S, Paredes-Casillas P, Landeros Navarro E, Bernard-Medina AG, Martinez-Bonilla G, Gutierrez-Urena S. Adverse events following immunization with vaccines containing adjuvants. Immunol Res. 2013;56(2–3):299–303.

    Article  CAS  PubMed  Google Scholar 

  27. Israeli E, Agmon-Levin N, Blank M, Shoenfeld Y. Adjuvants and autoimmunity. Lupus. 2009;18:1217–25.

    Article  CAS  PubMed  Google Scholar 

  28. Guimaraes LE, Baker B, Perricone C, Shoenfeld Y. Vaccines, adjuvants and autoimmunity. Pharmacol Res. 2015;100:190–209.

    Article  CAS  PubMed  Google Scholar 

  29. Ghimire TR, Benson RA, Garside P, Brewer JM. Alum increases antigen uptake, reduces antigen degradation and sustains antigen presentation by DCs in vitro. Immunol Lett. 2012;147(1–2):55–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kool M, Fierens K, Lambrecht BN. Alum adjuvant: some of the tricks of the oldest adjuvant. J Med Microbiol. 2012;61(Pt 7):927–34.

    Article  CAS  PubMed  Google Scholar 

  31. Cruz-Tapias P, Agmon-Levin N, Israeli E, Anaya JM, Shoenfeld Y. Autoimmune (Auto-inflammatory) syndrome induced by adjuvants (ASIA): animal models as a proof of concept. Curr Med Chem. 2013;20:4030–6.

    Article  CAS  PubMed  Google Scholar 

  32. Israeli E, Agmon-Levin N, Blank M, Shoenfeld Y. Macrophagic myofaciitis a vaccine (alum) autoimmune-related disease. Clin Rev Allergy Immunol. 2011;41(2):163–8.

    Article  CAS  PubMed  Google Scholar 

  33. Agmon-Levin N, Arango MT, Kivity S, Katzav A, Gilburd B, Blank M, et al. Immunization with hepatitis B vaccine accelerates SLE-like disease in a murine model. J Autoimmun. 2014;54:21–32.

    Article  CAS  PubMed  Google Scholar 

  34. Franchi L, Nunez G. The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity. Eur J Immunol. 2008;38(8):2085–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ulanova M, Tarkowski A, Hahn-Zoric M, Hanson LA. The Common vaccine adjuvant aluminum hydroxide up-regulates accessory properties of human monocytes via an interleukin-4-dependent mechanism. Infect Immun. 2001;69(2):1151–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ligi D, Santi M, Croce L, Mannello F. Aluminum induces inflammatory and proteolytic alterations in human monocytic cell line. J Inorg Biochem. 2015;152:190–8.

    Article  CAS  PubMed  Google Scholar 

  37. Dalakas MC. Inflammatory muscle diseases: a critical review on pathogenesis and therapies. Curr Opin Pharmacol. 2010;10(3):346–52.

    Article  CAS  PubMed  Google Scholar 

  38. Venalis P, Lundberg IE. Immune mechanisms in polymyositis and dermatomyositis and potential targets for therapy. Rheumatology (Oxford). 2014;53(3):397–405.

    Article  CAS  Google Scholar 

  39. O’Hanlon TP, Carrick DM, Arnett FC, Reveille JD, Carrington M, Gao X, et al. Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies. Medicine. 2005;84(6):338–49.

    Article  PubMed  Google Scholar 

  40. Gherardi RK, Authier FJ. Macrophagic myofasciitis: characterization and pathophysiology. Lupus. 2012;21:184–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Gherardi RK, Coquet M, Cherin P, Belec L, Moretto P, Dreyfus PA, et al. Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminium hydroxide in muscle. Brain. 2001;124:1821–31.

    Article  CAS  PubMed  Google Scholar 

  42. Sugiura T, Harigai M, Kawaguchi Y, Takagi K, Fukasawa C, Oshako-Higami S, et al. Increased IL-15 production of muscle cells in polymyositis and dermatomyositis. Int Immunol. 2002;14(8):917–24.

    Article  CAS  PubMed  Google Scholar 

  43. Lepidi H, Frances V, Figarella-Branger D, Bartoli C, Machado-Baeta A, Pellissier JF. Local expression of cytokines in idiopathic inflammatory myopathies. Neuropathol Appl Neurobiol. 1998;24:73–9.

    Article  CAS  PubMed  Google Scholar 

  44. Ronnblom L, Pascual V. The innate immune system in SLE: type I interferons and dendritic cells. Lupus. 2008;17(5):394–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Grammatikos AP, Tsokos GC. Immunodeficiency and autoimmunity: lessons from systemic lupus erythematosus. Trends Mol Med. 2012;18(2):101–8.

    Article  CAS  PubMed  Google Scholar 

  46. Tucci M, Quatraro C, Lombardi L, Pellegrino C, Dammacco F, Silvestris F. Glomerular accumulation of plasmacytoid dendritic cells in active lupus nephritis: role of interleukin-18. Arthritis Rheum. 2008;58(1):251–62.

    Article  CAS  PubMed  Google Scholar 

  47. Cusick MF, Libbey JE, Fujinami RS. Molecular mimicry as a mechanism of autoimmune disease. Clin Rev Allergy Immunol. 2012;42(1):102–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Doria A, Sarzi-Puttini P, Shoenfeld Y. Infections, rheumatism and autoimmunity: the conflicting relationship between humans and their environment. Autoimmun Rev. 2008;8(1):1–4.

    Article  PubMed  Google Scholar 

  49. Fourneau JM, Bach JM, van Endert PM, Bach JF. The elusive case for a role of mimicry in autoimmune diseases. Mol Immunol. 2004;40:1095–102.

    Article  CAS  PubMed  Google Scholar 

  50. Sfriso P, Ghirardello A, Botsios C, Tonon M, Zen M, Bassi N, et al. Infections and autoimmunity: the multifaceted relationship. J Leukoc Biol. 2010;87:385–95.

    Article  CAS  PubMed  Google Scholar 

  51. Aslanidis S, Pyrpasopoulou A, Kontotasios K, Doumas S, Zamboulis C. Parvovirus B19 infection and systemic lupus erythematosus: activation of an aberrant pathway? Eur J Intern Med. 2008;19(5):314–8.

    Article  PubMed  Google Scholar 

  52. Boele LC, Bajramovic JJ, De Vries AM, Voskamp-Visser IA, Kaman WE, Van Der Kleij D. Activation of toll-like receptors and dendritic cells by a broad range of bacterial molecules. Cell Immunol. 2009;255(1–2):17–25.

    Article  CAS  PubMed  Google Scholar 

  53. Lovgren T, Eloranta ML, Bave U, Alm GV, Ronnblom L. Induction of interferon-alpha production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG. Arthritis Rheum. 2004;50(6):1861–72.

    Article  PubMed  Google Scholar 

  54. Gottenberg JE, Chiocchia G. Dendritic cells and interferon-mediated autoimmunity. Biochimie. 2007;89:856–71.

    Article  CAS  PubMed  Google Scholar 

  55. Richardson SJ, Willcox A, Bone AJ, Morgan NG, Foulis AK. Immunopathology of the human pancreas in type-I diabetes. Semin Immunopathol. 2011;33(1):9–21.

    Article  CAS  PubMed  Google Scholar 

  56. Hviid A, Stellfeld M, Wohlfarhrt J, Melbye M. Childhood vaccination and type 1 diabetes. N Engl J Med. 2004;350(14):1398–404.

    Article  CAS  PubMed  Google Scholar 

  57. Coppieters KT, Roep BO, Von Herrath MG. Beta cells under attack: toward a better understanding of type 1 diabetes immunopathology. Semin Immunopathol. 2011;33(1):1–7.

    Article  PubMed  Google Scholar 

  58. Reynaud Q, Lega JC, Mismetti P, Chapelle C, Wahl D, Cathénebras P, et al. Risk of venous and arterial thrombosis according to type of antiphospholipid antibodies in adults without systemic lupus erythematosus: a systematic review and meta-analysis. Autoimmun Rev. 2014;13(6):595–608.

    Article  CAS  PubMed  Google Scholar 

  59. Blank M, Krause I, Fridkin M, Keller N, Kopolovic J, Goldberg I, et al. Bacterial induction of autoantibodies to β2-glycoprotein-I accounts for the infectious etiology of antiphospholipid syndrome. J Clin Investig. 2002;109(6):797–804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Inic-Kanada A, Stojanovic M, Zivkovic I, Kosec D, Micic M, Petrusic V, et al. Murine monoclonal antibody 26 raised against tetanus toxoid cross-reacts with beta2-glycoprotein I: its characteristics and role in molecular mimicry. Am J Reprod Immunol. 2009;61(1):39–51.

    Article  CAS  PubMed  Google Scholar 

  61. Zivkovic I, Stojanovic M, Petrusic V, Inic-Kanada A, Dimitrijevic L. Induction of APS after TTd hyper-immunization has a different outcome in BALB/c and C57BL/6 mice. Am J Reprod Immunol. 2011;65(5):492–502.

    Article  CAS  PubMed  Google Scholar 

  62. Petrusic V, Zivkovic I, Muhandes L, Dimitrijevic R, Stojanovic M, Dimitrijevic L. Infection-induced autoantibodies and pregnancy related pathology: an animal model. Reprod Fertil Dev. 2014;26(4):578–86.

    Article  CAS  PubMed  Google Scholar 

  63. Petrusic V, Todorovic N, Zivkovic I, Dimitrijević R, Muhandes L, Rajnpreht I, et al. Autoantibody response and pregnancy-related pathology induced by combined LPS and tetanus toxoid hyperimmunization in BALB/c and C57BL/6 mice. Autoimmunity. 2015;48(2):87–99.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine E, Meir Medical Center, Kfar-Saba (Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel), 44261, Kfar-Saba, Israel

    N. Ruhrman-Shahar, P. Rotman-Pikielny & Y. Levy

  2. Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

    J. Torres-Ruiz

Authors
  1. N. Ruhrman-Shahar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Torres-Ruiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Rotman-Pikielny
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y. Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. Levy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ruhrman-Shahar, N., Torres-Ruiz, J., Rotman-Pikielny, P. et al. Autoimmune reaction after anti-tetanus vaccination—description of four cases and review of the literature. Immunol Res 65, 157–163 (2017). https://doi.org/10.1007/s12026-016-8822-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-016-8822-x

Keywords

Search

Navigation