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

ABSTRACT: 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-? (IL-4R?) concentration, and T-cell membrane IL-4R? expression. T-cell IL-4R? expression also increased when mice that express human Fc? receptor I? were sensitized with IgG-depleted serum from a peanut-allergic individual and challenged with peanut extract. Increased T-cell IL-4R? 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-4R? expression in vitro. Murine IgG- but not IgE-mediated anaphylaxis was characterized by decreased neutrophil Fc? receptor III (Fc?RIII) expression that was observed even when the antigen dose was insufficient to induce shock. Human neutrophils cultured with IgG immune complexes also lost Fc?RIII. These observations suggest that decreased blood neutrophil Fc?RIII expression without increased IL-4R? expression can be used to determine whether and when IgG-mediated anaphylaxis occurs in man.

SUBMITTER: Khodoun MV

PROVIDER: S-EPMC3145724 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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

Khodoun Marat V MV Strait Richard R Armstrong Laura L Yanase Noriko N Finkelman Fred D FD

Proceedings of the National Academy of Sciences of the United States of America 20110711 30

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 sec ...[more]

PMID: 21746933

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Project description:Crosslinking of receptor-bound Immunoglobulin E (IgE) triggers immediate hypersensitivity reactions including anaphylaxis. Blocking the interaction of IgE with its high-affinity receptor, Fc?RI, on mast cells and basophils is an attractive strategy for the treatment of allergies. This approach has seen clinical success using the anti-IgE monoclonal antibody, omalizumab. We recently designed and characterized a novel Fc?RI-mimetic peptide (PepE) which contains the two key Fc?RI ?-chain receptor loops known to interact with the ?-heavy chain of IgE, C'-E and B-C, with an optimized linker for joining them. PepE has high specificity and affinity for IgE, blocks IgE binding to Fc?RI and prevents IgE-induced mediator release from RBL2H3 cells. We have now investigated the biological effects of this peptide in vivo using a line of mice (BALB/c Il4raF709) very sensitive to IgE-mediated systemic anaphylaxis. IgE-deficient (IgE-/-) Il4raF709 mice were passively sensitized with the anti-DNP IgE monoclonal antibody (SPE-7) and subsequently challenged i.v. with DNP-BSA. Mice receiving a single dose of PepE prior to sensitization with SPE-7 IgE were fully protected from anaphylaxis while vehicle control-treated mice displayed strong reactions with significant core body temperature drops and elevated levels of mouse mast cell protease-1 (mMCP-1) in the serum. However, PepE had no effect on IgE-mediated anaphylaxis if given after IgE administration in IgE-/- mice, suggesting that PepE can block binding of free IgE to Fc?RI but cannot compete with the receptor for already bound IgE in vivo. A single dose of PepE treatment did not protect IgE sufficient mice from IgE mediated anaphylaxis. However, a 3 week long course of PepE treatment protected IgE sufficient Il4raF709 mice from body temperature drops and elevation of serum mMCP-1. Our findings establish the potential of this type of structure for blocking IgE binding to mast cells in vivo and suggest that related peptides might have the potential to attenuate clinical allergic reactions.

Dataset Information

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

Publications

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

Similar Datasets

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