Induction and suppression of allergic diarrhea and systemic anaphylaxis in a murine model of food allergy

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• 作者：Zeynep Yesim Kucuk ; MD^a ; Richard Strait ; MD^b ; Marat V. Khodoun ; PhD^c ; ^d ; Ashley Mahler ; BA^b ; Simon Hogan ; PhD^a ; Fred D. Finkelman ; MD^d ; ^e ; ^f ; ^{ffinkelman@pol.net}
• 关键词：IgA ; IgE ; IgG ; J chain ; polymeric immunoglobulin receptor
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 期刊代码：158_00916749
• 类别：med
• 出版时间：May, 2012
• 卷：129
• 期：5
• 页码：1343-1348
• 文件大小：390 K

摘要

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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.