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

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-4R alpha) concentration, and T-cell membrane IL-4R alpha expression. T-cell IL-4R alpha expression also increased when mice that express human Fc epsilon receptor I alpha were sensitized with IgG-depleted serum from a peanut-allergic individual and challenged with peanut extract. Increased T-cell IL-4R alpha 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 alpha expression in vitro. Murine IgG-but not IgE-mediated anaphylaxis was characterized by decreased neutrophil Fc gamma receptor III (Fc gamma 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 gamma RIII. These observations suggest that decreased blood neutrophil Fc gamma RIII expression without increased IL-4R alpha expression can be used to determine whether and when IgG-mediated anaphylaxis occurs in man.