Ratios of specific IgG over IgE antibodies do not improve prediction of peanut allergy nor of its severity compared to specific IgE alone.

Mareen R Datema, Esben Eller, Aeilko H Zwinderman, Lars K Poulsen, Serge A Versteeg, Ronald van Ree, Carsten Bindslev-Jensen

Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 2020;49(2):216-226

PMID: 30269403

Plain Language Summary

plain language summary logo

Ara h 1, 2, 3 and 6 are major peanut allergens. Peanut allergy sufferers are sensitized to at least one of these allergens, which can increase their risk of allergy symptoms and anaphylactic reactions. A component-resolved diagnosis using IgE has become an indispensable tool for distinguishing between tolerance, allergy, and risk of severe reactions. The blocking antibodies IgG4, IgG, and IgA may counteract IgE antibodies. This clinical trial, therefore, investigated the associations between component-specific IgG, IgE, IgG4, IgA antibodies and whole peanut extract by analysing the severity of the outcome and assessing the diagnostic accuracy of antibody levels and ratios to determine the severity level of peanut allergy. One hundred and sixty-two peanut sensitised tolerant and allergic subjects were examined using immunoCAP for specific antibody isotypes against peanut extract, Ara h1, 2, 3, 8 and 9. According to the study, specific IgE against Ara h 2 is the best biomarker to diagnose peanut allergy, distinguish peanut-allergic subjects from tolerant sensitised subjects, and estimate the severity of the reaction. Additionally, the ratio of IgG and IgG4 antibodies over IgE did not improve predictive accuracy. This study provides healthcare professionals with insight into the role of different antibody isotypes in testing and diagnosing peanut allergies.

Abstract

BACKGROUND

IgG 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.

OBJECTIVE

To evaluate whether (a) peanut-specific IgG, IgG and/or IgA antibodies are associated with tolerance and/or less severe reactions and (b) 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 IgG . 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 IgG were also positively associated albeit significantly weaker (AUCs from 0.65 to 0.72). On the other hand, ratios of IgG and IgG 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 0.54 to 0.89).

CONCLUSION

IgE against Ara h 2 is the best biomarker for predicting peanut challenge outcomes including severity and IgG and IgG antibody ratios over IgE do not improve these outcomes.

© 2018 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

Address: Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands.; Department of Clinical Epidemiology, Academic Medical Centre, Biostatistics and Bioinformatics, Amsterdam, the Netherlands.; Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis (ORCA), Odense University Hospital, Odense, Denmark.; Department of Clinical Epidemiology, Academic Medical Centre, Biostatistics and Bioinformatics, Amsterdam, the Netherlands.; Allergy Clinic, Copenhagen University Hospital at Gentofte, Copenhagen, Denmark.; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands.; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands.; Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, the Netherlands.
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