Food, drug, insect sting allergy, and anaphylaxis
Induction and suppression of allergic diarrhea and systemic anaphylaxis in a murine model of food allergy

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Background

The clinical manifestations of food allergy include diarrhea and systemic anaphylaxis (shock), which can occur together or by themselves in different subjects. Although ingested food antigens need to be absorbed to induce shock, it is not known whether they need to be absorbed to induce diarrhea.

Objective

We sought to identify mechanisms that determine whether food allergy induces diarrhea versus shock and determine whether diarrhea requires absorption of ingested antigens.

Methods

These issues were studied in mice in active, passive, and hybrid immunization models. The active model was used to determine the allergic diarrhea susceptibility of J chain– and polymeric immunoglobulin receptor–deficient mice, which are unable to secrete IgA. The hybrid model was used to determine whether intravenously administered antigen-specific IgG antibody, which is not secreted into the gut, can protect against allergic diarrhea, as well as shock.

Results

Shock, but not diarrhea, was induced in naive mice by using intravenous IgE anti-trinitrophenyl (TNP) antibody, followed by oral TNP-BSA, whereas both were induced in mice presensitized with intraperitoneal ovalbumin/alum plus oral ovalbumin. More TNP-BSA was required to induce shock than diarrhea in presensitized mice, and intravenous IgG anti-TNP antibody, which is not secreted into the gut, protected these mice against both diarrhea and shock. Consistent with this, chicken ovalbumin–immunized J chain– and polymeric immunoglobulin receptor–deficient mice, which have high serum IgA levels but little intestinal IgA, resisted diarrhea induction.

Conclusion

Intestinal immunity and oral antigen dose determine whether diarrhea, systemic anaphylaxis, or both are induced, and ingested antigen must be absorbed to induce either response.

Section snippets

Mice

BALB/c-background wild-type (WT) and transgenic mice in which an IL-9 transgene is regulated by the intestinal fatty acid–binding protein promoter (iIL-9 Tgn mice),15 BALB/c-background polymeric immunoglobulin receptor (pIgR)–deficient mice (Jackson Laboratories, Bar Harbor, Me),16 BALB/c-background J-chain–deficient mice (a gift from Dennis Metzger, Albany Medical College, Albany, NY),17 and BALB/c-background FcγRIIb–deficient mice18 were all bred in house. All experimental procedures were

Passive immunization with IgE antibody is sufficient for antigen ingestion to induce shock, but not diarrhea, in immunologically naive mice

Initial experiments determined whether increased levels of antigen-specific IgE antibody are sufficient for ingestion of the targeted antigen to induce systemic shock, allergic diarrhea, or both. By itself, intravenous injection of WT mice with IgE anti-TNP mAb did not induce shock (hypothermia) or diarrhea (data not shown); however, OG of these IgE-primed mice the next day with 50 mg of TNP-BSA induced shock (hypothermia), although it did not induce diarrhea (Fig 1, A). To determine whether

Discussion

The studies described here (1) explain how allergic diarrhea and systemic anaphylaxis can each occur by itself in patients with food allergy and (2) demonstrate that even allergic diarrhea requires systemic absorption of ingested allergen. Our observation that passive immunization with IgE anti-TNP, followed by ingestion of TNP-BSA, causes shock but not diarrhea indicates that basal mast cell numbers and quantities of antigen absorption are sufficient to induce shock but not diarrhea. This

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    Supported by a Department of Veterans Affairs Merit Award (to F.D.F.), National Institutes of Health (NIH) grant R01 AI073553 (to S.H.), and an NIH T32 Training Grant (to Z.Y.K.).

    Disclosure of potential conflict of interest: S. Hogan has consultant arrangements with Immune Pharmaceuticals and receives research support from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest.

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