Anaphylaxis to a self-peptide in the absence of mast cells or histamine

Silvia Musio, Paola Pedotti, Renato Mantegazza, Hiroshi Ohtsu, Louis Boon, Lawrence Steinman, Stephen J. Galli, Rosetta Pedotti

Research output: Contribution to journalArticle

Abstract

Induction of T helper 1 (Th1) to Th2 deviation through administration of self- or altered self-peptides holds promise for treatment of autoimmunity. However, administration of self-peptides in models of autoimmunity can result in anaphylactic reactions. Although both IgE and IgG1 antibodies might be involved in the development of anaphylaxis to myelin peptides in experimental autoimmune encephalomyelitis in mice, the effector cells and molecules involved are not fully understood. Here we show that systemic anaphylaxis to the self-antigen myelin oligodendrocyte glycoprotein (MOG) 35-55 can occur in mice lacking mast cells (KitWKitW-v mice) or histamine (histidine decarboxylase-deficient mice), but is prevented in mice lacking IL-4. Treatment of mice with CV6209, a platelet-activating factor antagonist, slightly reduced the incidence of anaphylaxis to self-MOG35-55 in this model, but more effectively protected mice against anaphylaxis to this peptide when self-MOG35-55 was administered in a different immunization protocol that omitted the use of Bordetella pertussis toxin as an adjuvant at the time of immunization. Thus, anaphylactic reactions to self-MOG can occur in the absence of mast cells or histamine, key elements of the classical IgE-, mast cell-, and histamine-dependent pathway of anaphylaxis.

Original languageEnglish
Pages (from-to)398-405
Number of pages8
JournalLaboratory Investigation
Volume89
Issue number4
DOIs
Publication statusPublished - Apr 2009

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Keywords

  • Anaphylaxis
  • Experimental autoimmune encephalomyelitis
  • Histamine
  • IL-4
  • Mast cells
  • Self-peptide

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Molecular Biology

Cite this

Musio, S., Pedotti, P., Mantegazza, R., Ohtsu, H., Boon, L., Steinman, L., Galli, S. J., & Pedotti, R. (2009). Anaphylaxis to a self-peptide in the absence of mast cells or histamine. Laboratory Investigation, 89(4), 398-405. https://doi.org/10.1038/labinvest.2009.4