Skip to main content

Advertisement

SpringerLink
Log in

Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA syndrome) in commercial sheep

  • ETIO PATHOGENESIS OF AUTOIMMUNITY
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

We describe a form of the autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA syndrome) in commercial sheep, linked to the repetitive inoculation of aluminum-containing adjuvants through vaccination. The syndrome shows an acute phase that affects less than 0.5 % of animals in a given herd, it appears 2–6 days after an adjuvant-containing inoculation and it is characterized by an acute neurological episode with low response to external stimuli and acute meningoencephalitis, most animals apparently recovering afterward. The chronic phase is seen in a higher proportion of flocks, it can follow the acute phase, and it is triggered by external stimuli, mostly low temperatures. The chronic phase begins with an excitatory phase, followed by weakness, extreme cachexia, tetraplegia and death. Gross lesions are related to a cachectic process with muscular atrophy, and microscopic lesions are mostly linked to a neurodegenerative process in both dorsal and ventral column of the gray matter of the spinal cord. Experimental reproduction of ovine ASIA in a small group of repeatedly vaccinated animals was successful. Detection of Al(III) in tissues indicated the presence of aluminum in the nervous tissue of experimental animals. The present report is the first description of a new sheep syndrome (ovine ASIA syndrome) linked to multiple, repetitive vaccination and that can have devastating consequences as it happened after the compulsory vaccination against bluetongue in 2008. The ovine ASIA syndrome can be used as a model of other similar diseases affecting both human and animals. A major research effort is needed in order to understand its complex pathogenesis.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Zandman-Goddard G, Blank M, Ehrenfeld M, Gilburd B, Peter J, Shoenfeld Y. A comparison of autoantibody production in asymptomatic and symptomatic women with silicone breast implants. J Rheumatol. 1999;26:73–7.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Shoenfeld Y, Agmon-Levin N. ‘ASIA’—autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011;36:4–8.

    Article  PubMed  CAS  Google Scholar 

  4. Israeli E. Gulf War syndrome as a part of the autoimmune (autoinflammatory) syndrome induced by adjuvant (ASIA). Lupus. 2012;21:190–4.

    Article  PubMed  CAS  Google Scholar 

  5. Baylor NW, Egan W, Richman P. Aluminum salts in vaccines-US perspective. Vaccine. 2002;20(Suppl 3):S18–23.

    Article  PubMed  CAS  Google Scholar 

  6. Kumar V, Gill KD. Aluminium neurotoxicity: neurobehavioural and oxidative aspects. Arch Toxicol. 2009;83:965–78.

    Article  PubMed  CAS  Google Scholar 

  7. Exley C, Swarbrick L, Gherardi RK, Authier FJ. A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome. Med Hypotheses. 2009;72:135–9.

    Article  PubMed  CAS  Google Scholar 

  8. Tomljenovic L, Shaw CA. Aluminum vaccine adjuvants: are they safe? Curr Med Chem. 2011;18:2630–7.

    Article  PubMed  CAS  Google Scholar 

  9. Eisenbarth SC, Colegio OR, O’Connor W, Sutterwala FS, Flavell RA. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature. 2008;453:1122–6.

    Article  PubMed  CAS  Google Scholar 

  10. Marrack P, McKee AS, Munks MW. Towards an understanding of the adjuvant action of aluminium. Nat Rev Immunol. 2009;9:287–93.

    Article  PubMed  CAS  Google Scholar 

  11. Exley C, Siesjö P, Erikssson H. The immunobiology of aluminium adjuvants: how do they really work? Trends Immunol. 2010;31:103–9.

    Article  PubMed  CAS  Google Scholar 

  12. González JM, Figueras L, Ortega ME, Lozano M, Ruíz de Arcaute M, Royo R, Cebrián LM, Ferrer LM, Fariñas F, de Jalón JA, de las Heras M. Possible adverse reactions in sheep after vaccination with inactivated BTV vaccines. Vet Rec. 2010;166:757–8.

    Article  PubMed  Google Scholar 

  13. Tourbah A, Gout O, Liblau R, Lyon-Caen O, Bougniot C, Iba-Zizen MT, Cabanis EA. Encephalitis after hepatitis B vaccination: recurrent disseminated encephalitis or MS? Neurology. 1999;53:396–401.

    Article  PubMed  CAS  Google Scholar 

  14. Huynh W, Cordato DJ, Kehdi E, Masters LT, Dedousis C. Post-vaccination encephalomyelitis: literature review and illustrative case. J Clin Neurosci. 2008;15:1315–22.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  16. Yang YQ, Li JC. Progress of research in cell-in-cell phenomena. Anat Rec. 2012;295:372–7.

    Article  Google Scholar 

  17. Guis S, Pellissier JF, Nicoli F, Reviron D, Mattei JP, Gherardi RK, Pelletier J, Kaplanski G, Figarella-Branger D, Roudier J. HLA-DRB1*01 and macrophagic myofasciitis. Arthritis Rheum. 2002;46:2535–7.

    Article  PubMed  CAS  Google Scholar 

  18. Divers TJ, Mohammed HO, Cummings JF. Equine motor neuron disease. Vet Clin North Am Equine Pract. 1997;13:97–105.

    PubMed  CAS  Google Scholar 

  19. Couette M, Boisse MF, Maison P, Brugieres P, Cesaro P, Chevalier X, Gherardi RK, Bachoud-Levi AC, Authier FJ. Long-term persistence of vaccine-derived aluminum hydroxide is associated with chronic cognitive dysfunction. J Inorg Biochem. 2009;103:1571–8.

    Article  PubMed  CAS  Google Scholar 

  20. Shaw CA, Petrik MS. Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration. J Inorg Biochem. 2009;103:1555–62.

    Article  PubMed  CAS  Google Scholar 

  21. Trendelenburg G. Acute neurodegeneration and the inflammasome: central processor for danger signals and the inflammatory response? J Cereb Blood Flow Metab. 2008;28:867–81.

    Article  PubMed  CAS  Google Scholar 

  22. Shi F, Yang L, Kouadir M, Yang Y, Wang J, Zhou X, Yin X, Zhao D. The NALP3 inflammasome is involved in neurotoxic prion peptide-induced microglial activation. J Neuroinflammation. 2012;9:73.

    Article  PubMed  CAS  Google Scholar 

  23. Kubota T, Koike R. Cryopyrin-associated periodic syndromes: background and therapeutics. Mod Rheumatol. 2010;20:213–21.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work has been possible thanks to the interest and effort of many veterinarians and farmers that are all deeply acknowledged. We are indebted to many colleagues that helped with many analyses of ovine samples. We are also very thankful to Rosario Puyó and Santiago Becerra for technical help.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Animal Pathology, Veterinary Faculty, University of Zaragoza, 177 Miguel Servet street, 50013, Saragossa, Spain

    Lluís Luján, Marta Pérez, Eider Salazar, Neila Álvarez, Marina Gimeno, Pedro Pinczowski & Nerea Insausti

  2. Aragon Nanoscience Institute (INA), Department of Chemical Engineering, University of Zaragoza, Saragossa, Spain

    Silvia Irusta & Jesús Santamaría

  3. Gabinete Técnico Veterinario (GTV), Saragossa, Spain

    Yerzol Cortés & Luis Figueras

  4. Equipo Técnico Veterinario Oviaragón S.C.L., Saragossa, Spain

    Isabel Cuartielles & Enrique Fantova

  5. Sociedad Cooperativa Limitada Agropecuaria del Sobrarbe (SCLAS), Aínsa, Spain

    Miguel Vila & José Luis Gracia Chapullé

Authors
  1. Lluís Luján
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marta Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eider Salazar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Neila Álvarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marina Gimeno
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pedro Pinczowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Silvia Irusta
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jesús Santamaría
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nerea Insausti
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yerzol Cortés
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Luis Figueras
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Isabel Cuartielles
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Miguel Vila
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Enrique Fantova
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. José Luis Gracia Chapullé
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lluís Luján.

Additional information

José Luis Gracia Chapullé: Deceased.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Luján, L., Pérez, M., Salazar, E. et al. Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA syndrome) in commercial sheep. Immunol Res 56, 317–324 (2013). https://doi.org/10.1007/s12026-013-8404-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-013-8404-0

Keywords

Search

Navigation