Serum but not secreted Ag-specific IgA inhibits oral Ag induced anaphylaxis. (97.6)

Abstract

Abstract Epidemiologic evidence suggests that IgA, the main mucosal Ig isotype, inhibits allergy, but it is not known whether it suppresses anaphylaxis. We used mouse models to evaluate whether IgA can suppress systemic anaphylactic responses to ingested allergens by neutralizing them before or after their systemic absorption. Passive systemic anaphylaxis (PSA), measured as hypothermia, was induced by sensitizing mice with IgE anti-TNP mAb, then challenging them orally (og) with TNP-OVA. The ability of IgA to inhibit PSA by neutralizing Ag prior to or after systemic absorption was evaluated by pretreating mice with IgA anti-TNP mAb either og or iv. TNP-OVA was detectible in serum by 5 min after og administration. PSA developed within 5 min and was inhibited by iv, but not og IgA. Extent of inhibition was proportional to the IgA dose and Fcα/μR- and FcγRIIb-independent. Intestinal anaphylaxis (IA), defined as diarrhea <60 minutes after OVA challenge, was induced by priming mice ip with OVA/alum, then challenging them og 3x/wk with OVA. IA development was delayed in J-chain- and PIgR-deficient mice, which have markedly increased serum IgA and decreased intestinal IgA. Thus, Ag-specific IgA acts in the blood but not the gut to inhibit systemic and intestinal anaphylaxis. This indicates that ingested antigen must be absorbed systemically to induce systemic anaphylaxis and suggests that immunotherapy should aim at increasing blood, rather than gut levels of non-IgE Abs to food allergens.