Transiently increased serum ferritin is a marker for IgG-mediated murine anaphylaxis

Although anaphylaxis is classically mediated by IgE, mast cells (MCs), and FcεRI, mouse experiments and clinical observations demonstrate an alternative pathway mediated by IgG, IgGFc receptors, and several cell types.

We sought to determine whether increased serum ferritin distinguishes IgG-mediated anaphylaxis from IgE-mediated anaphylaxis and to identify the mechanism for its increase.

Passive and active systemic anaphylaxis was induced, respectively, by injecting mice with an IgE or IgG anti-trinitrophenyl mAb and challenged with trinitrophenyl-ovalbumin, or by injecting mice with goat anti-mouse IgD antiserum and challenged with goat IgG. Readouts were hypothermia and hypomobility. Inhibitors were used to investigate cell types and molecules involved. Serum ferritin was quantitated by ELISA.

IgG-mediated, but not IgE-mediated, anaphylaxis induced a severalfold increase in serum ferritin level beginning less than 0.5 hours after antigen challenge and lasting 24 to 36 hours. Polymorphonuclear leukocytes, MCs, and histamine contributed to the ferritin response, but histamine and platelet-activating factor were insufficient to induce the response, which was oxidation-dependent but shock-independent. Small ferritin responses were generated by mouse and human blood cells cultured with immune complexes and/or histamine.

IgG-mediated, but not IgE-mediated, anaphylaxis in mice is associated with a large, rapid, relatively long-lasting increase in serum ferritin that depends on neutrophils, MCs, oxidation, and histamine. Initial data suggest that immune complexes also increase ferritin in humans. Quantitation of serum ferritin should provide a way to detect IgG-mediated anaphylaxis and could help identify the optimal way to detect and treat anaphylaxis.