Ratios of specific IgG 4 over IgE antibodies do not improve prediction of peanut allergy nor of its severity compared to specific IgE alone Running title : Diagnostic predictive value of IgG 4-IgE ratio not better than of

Background: IgG(4) antibodies have been suggested to play a protective role in the translation of peanut sensitization into peanut allergy. Whether they have added value as diagnostic read-out has not yet been reported. A cc ep te d A rt ic le This article is protected by copyright. All rights reserved. Objective: To evaluate whether (1) peanut specific IgG, IgG4 and/or IgA antibodies are associated with tolerance and/or less severe reactions, and (2) they can improve IgE-based diagnostic tests. Methods: Sera of 137 patients with challenge-proven peanut allergy and of 25 subjects that tolerated peanut, both with known IgE profiles to peanut extract and five individual peanut allergens, were analyzed for specific IgG and IgG4. Antibody levels and ratios thereof were associated with challenge outcome including symptom severity grades. For comparison of the discriminative performance, receiver operating characteristic curve (ROC) analysis was used. Results: IgE against Ara h 2 was significantly higher in allergic than in tolerant patients and associated with severity of reactions (p<0.001) with substantial diagnostic capability (AUC 0.91, 95%CI 0.87-0.96 and 0.80, 95%CI 0.73-0.87, respectively). IgG and IgG4 were also positively associated albeit significantly weaker (AUCs from 0.65 to 0.72). On the other hand, ratios of IgG and IgG4 over IgE were greater in patients that were tolerant or had mild symptoms as compared to severe patients but they did not predict challenge outcomes better than IgE alone (AUCs from 0.540.89). Conclusion: IgE against Ara h 2 is the best biomarker for predicting peanut challenge outcomes including severity and IgG and IgG4 antibody ratios over IgE do not improve these outcomes.