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.
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References
Shoenfeld Y, Agmon-Levin N, Tomljenovic L. Vaccines and autoimmunity. Vancouver: Wiley-Blackwell; 2015.
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.
Salami S, D’Amelio R. Could autoimmunity be induced by vaccination? Int Rev Immunol. 2010;29(3):247–69.
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.
Wraith DC. Vaccination an autoimmune diseases: what is the evidence? Lancet. 2003;362(9396):1659–66.
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.
Shoenfeld Y, Agmon-Levin N. ASIA autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011;36(1):4–8.
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.
Petrovsky N, Aguilar JC. Vaccine adjuvants: current state and future trends. Immunol Cell Biol. 2004;82(5):488–96.
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.
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.
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.
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.
Cines DB, Liebman H, Stasi R. Pathobiology of secondary immune thrombocytopenia. Semin Hematol. 2009;46:S2–14.
Marks JS, Halpin TJ. Guillain–Barré syndrome in recipients of A/New Jersey influenza vaccine. JAMA. 1980;243(24):2490–4.
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.
Eisen DP, McBryde ES. Avoiding Guillain–Barré syndrome following swine origin pandemic H1N1 2009 influenza vaccination. J Infect Dis. 2009;200(10):1627–8.
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.
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.
Hassan W, Oldham R. Reiter’s syndrome and reactive arthritis in health care workers after vaccination. BMJ. 1994;309(6947):94.
Aksu K, Keser G, Doganavsargil E. Reactive arthritis following tetanus and rabies vaccinations. Rheumatol Int. 2006;27(2):209–10.
Agmon-Levin N, Zafrir Y, Paz Z. Ten cases of systemic lupus erythematosus related to hepatitis B vaccine. Lupus. 2009;18(13):1192–7.
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.
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.
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.
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.
Israeli E, Agmon-Levin N, Blank M, Shoenfeld Y. Adjuvants and autoimmunity. Lupus. 2009;18:1217–25.
Guimaraes LE, Baker B, Perricone C, Shoenfeld Y. Vaccines, adjuvants and autoimmunity. Pharmacol Res. 2015;100:190–209.
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.
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.
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.
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.
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.
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.
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.
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.
Dalakas MC. Inflammatory muscle diseases: a critical review on pathogenesis and therapies. Curr Opin Pharmacol. 2010;10(3):346–52.
Venalis P, Lundberg IE. Immune mechanisms in polymyositis and dermatomyositis and potential targets for therapy. Rheumatology (Oxford). 2014;53(3):397–405.
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.
Gherardi RK, Authier FJ. Macrophagic myofasciitis: characterization and pathophysiology. Lupus. 2012;21:184–9.
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.
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.
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.
Ronnblom L, Pascual V. The innate immune system in SLE: type I interferons and dendritic cells. Lupus. 2008;17(5):394–9.
Grammatikos AP, Tsokos GC. Immunodeficiency and autoimmunity: lessons from systemic lupus erythematosus. Trends Mol Med. 2012;18(2):101–8.
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.
Cusick MF, Libbey JE, Fujinami RS. Molecular mimicry as a mechanism of autoimmune disease. Clin Rev Allergy Immunol. 2012;42(1):102–11.
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.
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.
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.
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.
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.
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.
Gottenberg JE, Chiocchia G. Dendritic cells and interferon-mediated autoimmunity. Biochimie. 2007;89:856–71.
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.
Hviid A, Stellfeld M, Wohlfarhrt J, Melbye M. Childhood vaccination and type 1 diabetes. N Engl J Med. 2004;350(14):1398–404.
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.
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.
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.
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.
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.
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.
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.
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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
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DOI: https://doi.org/10.1007/s12026-016-8822-x