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An unexpected version of horror autotoxicus: anaphylactic shock to a self-peptide

Nature Immunology volume 2, pages 216–222 (2001)Cite this article

Abstract

EAE can refer either to experimental autoimmune encephalomyelitis or experimental allergic encephalomyelitis. Although EAE is classically a prototypic T helper 1 (TH1) cell–mediated autoimmune disease, it can also be induced by TH2 cells. Characteristically, the most severe manifestation of allergy, anaphylaxis, is associated with exposure to a foreign antigen that is often derived from medication, insect venom or food. We report here that, after self-tolerance to myelin is destroyed, anaphylaxis may be triggered by a self-antigen, in this case a myelin peptide. “Horror autotoxicus”, which was initially described by Ehrlich, may not only include autoimmunity to self, it may also encompass immediate hypersensitivity to self, which leads to shock and rapid death.

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Figure 1: Challenge with soluble PLPp(139–151) after the acute phase of EAE causes signs of anaphylactic shock.
Figure 2: The reactions that occur after challenge with PLPp(139–151) are associated with a drop in body temperature and an increase in enhanced respiratory pause.
Figure 3: Histopathology of tissue sections obtained from a 12-week-old SJL/J mouse that was killed when it became moribund 20 min after apparent anaphylaxis.
Figure 4: Titers of anti-PLPp(139–151) of the IgG1 isotype progressively increased during the course of EAE compared to IgG2a and to total IgE.
Figure 5: Mice with EAE that develop anaphylactic shock after challenge with native PLPp(139–151) exhibit a much lower mast cell degranulation compared to mice that developed IgE-dependent anaphylaxis.
Figure 6: Absence of allergic reactions after challenge with MBPAc(1–11) or with PLPp(178–191) is confirmed by the absence of changes in body temperature.

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Acknowledgements

We thank Z-S. Wang for technical assistance and H. McDevitt, T. Staehelin, A. Pedotti, P. Decamilli, P. Ghezzi and L. Stark for critical reading of the manuscript. Supported (in part) by a postdoctoral fellowship from the National Multiple Sclerosis Society (to R. P.) and support from the National Institutes of Health and the Phil N. Allen Fund.

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Authors and Affiliations

  1. Department of Neurology and Neurological Science, Stanford University Medical Center, Stanford, 94305, CA, USA

    Rosetta Pedotti, Dennis Mitchell, Marcela Karpuj, Dorothée Chabas & Lawrence Steinman

  2. Institute of Clinical Neurology, University of Milan, IRCCS Ospedale Maggiore Policlinico, Milan, Italy

    Rosetta Pedotti

  3. Department of Pathology, Stanford University Medical Center, Stanford, 94305, CA, USA

    Jochen Wedemeyer, Eyas M. Hattab, Mindy Tsai & Stephen J. Galli

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Pedotti, R., Mitchell, D., Wedemeyer, J. et al. An unexpected version of horror autotoxicus: anaphylactic shock to a self-peptide. Nat Immunol 2, 216–222 (2001). https://doi.org/10.1038/85266

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