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Publication : Identification of markers that distinguish IgE- from IgG-mediated anaphylaxis.

First Author  Khodoun MV Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  30 Pages  12413-8
PubMed ID  21746933 Mgi Jnum  J:174528
Mgi Id  MGI:5139936 Doi  10.1073/pnas.1105695108
Citation  Khodoun MV, et al. (2011) Identification of markers that distinguish IgE- from IgG-mediated anaphylaxis. Proc Natl Acad Sci U S A 108(30):12413-8
abstractText  IgG-mediated anaphylaxis occurs in mice and may contribute to human reactions to infused drugs. To distinguish IgE- from putative IgG-mediated human anaphylaxis, we developed blood markers for murine anaphylaxis and evaluated their human relevance. Both IgG- and IgE-mediated anaphylaxis were characterized by decreased basophil and monocyte percentages and an increased neutrophil percentage in mouse blood. IgE- but not IgG-mediated murine anaphylaxis was accompanied by large increases in IL-4 secretion, plasma soluble IL-4 receptor-alpha (IL-4Ralpha) concentration, and T-cell membrane IL-4Ralpha expression. T-cell IL-4Ralpha expression also increased when mice that express human Fcepsilon receptor Ialpha were sensitized with IgG-depleted serum from a peanut-allergic individual and challenged with peanut extract. Increased T-cell IL-4Ralpha expression is likely to also be a marker for human IgE-mediated anaphylaxis, because IgE-activated human basophils secrete IL-4, and IL-4 increases human T-cell IL-4Ralpha expression in vitro. Murine IgG- but not IgE-mediated anaphylaxis was characterized by decreased neutrophil Fcgamma receptor III (FcgammaRIII) expression that was observed even when the antigen dose was insufficient to induce shock. Human neutrophils cultured with IgG immune complexes also lost FcgammaRIII. These observations suggest that decreased blood neutrophil FcgammaRIII expression without increased IL-4Ralpha expression can be used to determine whether and when IgG-mediated anaphylaxis occurs in man.
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