Ratios of specific IgG4 over IgE antibodies do not improve prediction of peanut allergy nor of its severity compared to specific IgE alone

M R Datema, E Eller, A H Zwinderman, L K Poulsen, S AVersteeg, R van Ree, Carsten Bindslev-Jensen

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Abstract

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. Objective: To evaluate whether (a) peanut-specific IgG, IgG 4 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 4. 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 4 were also positively associated albeit significantly weaker (AUCs from 0.65 to 0.72). On the other hand, ratios of IgG and IgG 4 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 4 antibody ratios over IgE do not improve these outcomes.

Original languageEnglish
JournalClinical and Experimental Allergy
Volume49
Issue number2
Pages (from-to)216-226
ISSN0954-7894
DOIs
Publication statusPublished - Feb 2019

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Peanut Hypersensitivity
Area Under Curve
Routine Diagnostic Tests
ROC Curve
Allergens
Arachis

Bibliographical note

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

Keywords

  • IgE
  • IgG
  • diagnosis
  • peanut allergy
  • symptom severity

Cite this

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title = "Ratios of specific IgG4 over IgE antibodies do not improve prediction of peanut allergy nor of its severity compared to specific IgE alone",
abstract = "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. Objective: To evaluate whether (a) peanut-specific IgG, IgG 4 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 4. 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 4 were also positively associated albeit significantly weaker (AUCs from 0.65 to 0.72). On the other hand, ratios of IgG and IgG 4 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 4 antibody ratios over IgE do not improve these outcomes.",
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Ratios of specific IgG4 over IgE antibodies do not improve prediction of peanut allergy nor of its severity compared to specific IgE alone. / Datema, M R; Eller, E; Zwinderman, A H; Poulsen, L K; AVersteeg, S; van Ree, R; Bindslev-Jensen, Carsten.

In: Clinical and Experimental Allergy, Vol. 49, No. 2, 02.2019, p. 216-226.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Ratios of specific IgG4 over IgE antibodies do not improve prediction of peanut allergy nor of its severity compared to specific IgE alone

AU - Datema, M R

AU - Eller, E

AU - Zwinderman, A H

AU - Poulsen, L K

AU - AVersteeg, S

AU - van Ree, R

AU - Bindslev-Jensen, Carsten

N1 - © 2018 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

PY - 2019/2

Y1 - 2019/2

N2 - 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. Objective: To evaluate whether (a) peanut-specific IgG, IgG 4 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 4. 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 4 were also positively associated albeit significantly weaker (AUCs from 0.65 to 0.72). On the other hand, ratios of IgG and IgG 4 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 4 antibody ratios over IgE do not improve these outcomes.

AB - 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. Objective: To evaluate whether (a) peanut-specific IgG, IgG 4 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 4. 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 4 were also positively associated albeit significantly weaker (AUCs from 0.65 to 0.72). On the other hand, ratios of IgG and IgG 4 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 4 antibody ratios over IgE do not improve these outcomes.

KW - IgE

KW - IgG

KW - diagnosis

KW - peanut allergy

KW - symptom severity

U2 - 10.1111/cea.13286

DO - 10.1111/cea.13286

M3 - Journal article

C2 - 30269403

VL - 49

SP - 216

EP - 226

JO - Clinical and Experimental Allergy

JF - Clinical and Experimental Allergy

SN - 0954-7894

IS - 2

ER -