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Vol. 99. Issue 4.
Pages 315-321 (July - August 2023)
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Vol. 99. Issue 4.
Pages 315-321 (July - August 2023)
Review article
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Biomarkers associated with persistence and severity of IgE-mediated food allergies: a systematic review
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Mariana Malucellia,b,c,d,
Corresponding author
mariana.malucelli@hc.ufpr.br

Corresponding author.
, Roque Farias Juniore, Rosiane Guetter Melloa,b,e, Carolina Prandoa,b,c,e
a Faculdades Pequeno Príncipe, Pós-Graduação em Biotecnologia Aplicada à Saúde da Criança e do Adolescente, Curitiba, PR, Brazil
b Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, PR, Brazil
c Hospital Pequeno Príncipe, Serviço de Alergia e Imunologia Pediátrica, Curitiba, PR, Brazil
d Complexo Hospital de Clinicas - Ebserh, UFPR, Curitiba, PR, Brazil
e Faculdades Pequeno Príncipe, Curso de Medicina, Curitiba, PR, Brazil
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Table 1. Article identification and Newcastle-Ottawa Scale (NOS) score.
Abstract
Objective

The prevalence of food allergies (FA) has increased worldwide over the last few decades. Milk, eggs, and peanuts are among the most common allergens and can cause anaphylaxis. Therefore, we aimed to identify biomarkers that could predict the persistence and/or severity of IgE-mediated allergies to milk, eggs, and peanuts via a systematic review.

Methods

This systematic review proceeded according to a protocol registered in the International Prospective Register of Systematic Reviews. Two independent authors extracted studies of interest from PubMed, SciELO, EMBASE, Scopus, and Ebsco databases and assessed their quality using the Newcastle-Ottawa Scale.

Results

We selected 14 articles describing 1,398 patients. Among eight identified biomarkers, total IgE, specific IgE (sIgE), and IgG4 were the most often cited biomarkers of persistent allergies to milk, eggs, and peanuts. Skin prick tests, endpoint tests, and sIgE cutoff levels may predict positive responses to challenges with these foods. The basophil activation test is a biomarker for the severity and/or threshold of allergic reactions to milk and peanuts.

Conclusion

Only a few publications identified possible prognostic indicators of the persistence or severity of FA and outcomes of oral food challenges, indicating that more accessible biomarkers are needed to determine the likelihood of having a severe food allergic reaction.

Keywords:
Biomarkers
Food allergy
Anaphylaxis
Oral food challenge
Allergy severity
Full Text
Introduction

Immunoglobulin E (IgE)-mediated food allergy (FA), an immunological response that can occur after exposure to food, has become a global public health problem.1,2 The prevalence of FA has increased over the last few decades and is considered to affect up to 45 million children and 12 million adults worldwide.2-4 Food allergies affect the quality of life of patients and their families, impact their daily activities, and can become life-threatening.2,5,6 More than 170 foods are possible causes of allergic reactions.7 Although FAs are the main cause of anaphylaxis, the risk of anaphylaxis due to food ingestion in patients with FAs has not been defined.8 The most common foods that cause allergies are milk, eggs, and peanuts; however, it is difficult to determine their prevalence due to regional variations.9,10

The effectiveness and safety of FA prevention measures remain undetermined. Preventive approaches, such as breastfeeding and the early introduction of some foods, can induce oral tolerance.11-13 Oral immunotherapy has also been used as a treatment; however, it can be associated with an increased incidence of allergic side effects, and patients do not always achieve tolerance.14,15 An allergenic food can be omitted from the diet, but accidental ingestion can lead to severe and occasionally fatal reactions.8,7,16 Current technological developments provide a deeper understanding of key immune cells and molecular mechanisms associated with FA, which might facilitate the safe treatment of different FA phenotypes and endotypes using precision medicine.17,18 The characterization of sensitive and specific biomarkers can improve diagnostic accuracy and guide decisions concerning the prevention, diagnosis, and management of FA.17

Although FA can be diagnosed using in vivo and in vitro tests, the gold standard remains the oral food challenge (OFC). Double-blind placebo-controlled food challenges (DBPFC) are expensive, time-consuming, labor-intensive, and limited to well-equipped clinics or hospitals; further, they can be potentially dangerous, because they can trigger anaphylactic reactions.19-21 Patients who are sensitized to a portion of food based only on clinical history or being positive in a screening test might not react to the same food in a DBPFC, implying that sensitization does not necessarily indicate the presence of food allergies.4,19 Therefore, diagnostic tools are needed to improve accuracy and guide decisions concerning the prevention, management, and treatment of FAs.17,22,23

This systematic review aimed to identify biomarkers that could predict the persistence and/or severity of egg, milk and peanut IgE-mediated allergy. Biomarkers could be useful to recognize patients with FAs who have become tolerant to a specific food and would not require an exclusion diet. Moreover, biomarkers could also identify patients with allergies who could have a severe reaction to an OFC and avoid exposing them to harmful events such as a severe anaphylactic reaction.

Methods

This systematic review proceeded according to a protocol registered in the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42020185609) and has been reported according to the PRISMA statement.24

Data sources and search strategy

We searched the PubMed, SciELO, EMBASE, Scopus, and Ebsco databases for studies of food allergies using the terms, “biomarker” AND “food” AND “allergy” in the title and abstract. Articles were limited to those published in English in the last decade. We limited the search to this time frame to access the most recent data on biomarkers. The search results were managed using Mendeley software. Duplicate articles were excluded from the analysis. The searches were repeated before the final analysis.

Study exclusion criteria

All titles, followed by abstracts, were screened for relevance using the following exclusion criteria: animal studies; languages other than English; studies of food allergies that did not include milk, eggs, and/or peanuts, and non-IgE-mediated food allergies. All relevant full-text articles were screened based on the following exclusion criteria: non-original articles, only congress abstracts available without a description of the study, and full-text unavailable. Systematic reviews, meta-analyses, cross-sectional studies, conference abstracts, case reports, case series, non-original articles, and animal studies were excluded.

Study eligibility criteria

We included articles on all studies that identified a biomarker related to the persistence or severity of IgE-mediated milk, egg, and/or peanut allergy and were conducted on children and adults of any age, with IgE-mediated food allergies to milk, eggs and/or peanuts. All patients were confirmed to have allergies using skin prick tests (SPTs), serum-specific IgE (sIgE), and/or OFC. All articles were independently assessed by two authors (MM and RF).

Data extraction

The two independent authors extracted data from the selected studies. They screened titles and abstracts and excluded those that were not related to the predetermined inclusion criteria. Full texts were obtained from the selected articles. Disagreements were resolved by consultation with a third author (CP). All studies were independently assessed and extensively discussed by all authors. The authors documented the extracted data (reference, first author, type of food, biomarker, and the number of patients included) from the articles using Excel spreadsheets.

Qualitative grading

We assessed the methodological quality evaluation and risk of bias in the included studies using the validated Newcastle-Ottawa Scale (NOS), which contains eight items within three domains: selection of study groups, comparability of groups, and ascertainment of exposure/outcomes. Scores of 0–3, 4–6, and 7–9 indicated low-, moderate-, and high-quality studies, respectively.25

Data synthesis

All descriptive analyses were performed in an Excel spreadsheet, shared by the authors (MM, RF, CP) after deciding which articles would be included in the systematic review.

ResultsSearch outcomes

The search identified 1196 articles among which, 318 were duplicated, and 634 were excluded after screening the title and abstract. Full texts were then obtained from 244 articles. The analysis of study type excluded 63 reports that were not original, resulting in 181 articles. Analyses of the food allergies described led to the exclusion of 143 articles that were not related to peanuts, milk, or eggs. Another 25 of 38 reports were excluded because they did not meet the inclusion criteria for biomarker function. Most of them were diagnostic, and not directly related to the persistence or severity of FA.

The search was repeated before the final analysis, which led to the inclusion of an additional study.26 We finally included 14 studies (Figure 1) comprising 1398 patients, of whom 48 were allergic to two or three foods, and 1350 were allergic only to eggs (n = 256), milk (n = 370), or peanuts (n = 724).

Figure 1.

PRISMA flow diagram.

(0.25MB).
Risk of bias and quality assessment

Risk of bias and quality was assessed using the NOS, and each included study was scored on the selection of participants, comparability, and outcome standards indicated by the NOS. The quality of one article was scored as moderate, whereas the others were classified as high-quality articles (Table 1).

Table 1.

Article identification and Newcastle-Ottawa Scale (NOS) score.

ARTICLE AUTHOR  ARTICLE NUMBER  ARTICLE TITLE  NOS SCORE 
Vazquez-Ortiz et al.  Ovalbumin-specific IgE/total IgE ratio improves the prediction of tolerance development in egg-allergic children aged >/=5 years 
Brossard et al.  Relative reactivity to egg white and yolk or change upon heating as markers for baked egg tolerance 
Sindher et al.  Analysis of a large standardized food challenge data set to determine predictors of positive outcome across multiple allergens 
Winberg et al.  Dynamics of cytokine mRNA expression and fecal biomarkers in school-children undergoing a double-blind placebo-controlled food challenge series 
Caubet et al.  Significance of ovomucoid- and ovalbumin-specific IgE/IgG4 ratios in egg allergy 
Ford et al.  Basophil reactivity, wheal size, and immunoglobulin levels distinguish degrees of cow's milk tolerance. 
Bellini et al.  Cow's milk allergy (CMA) in children: identification of allergologic tests predictive of food allergy 
Ahrens et al.  Individual cow's milk allergens as prognostic markers for tolerance development? 
Koike et al.  Predictors of Persistent Milk Allergy in Children: A Retrospective Cohort Study 
Lin et al.  10  A bioinformatics approach to identify patients with symptomatic peanut allergy using peptide microarray immunoassay 
Van Nieuwaal et al.  11  Utility of peanut-specific IgE levels in predicting the outcome of double-blind, placebo-controlled food challenges 
Santos et al.  12  Distinct parameters of the basophil activation test reflect the severity and threshold of allergic reactions to peanut. 
Chinthrajah et al.  13  Development of a tool predicting severity of allergic reaction during peanut challenge 
Santos et al.  14  Biomarkers of severity and threshold of allergic reactions during oral peanut challenge 
Biomarkers

We identified the following biomarkers in the 14 studies: positive SPT and endpoint test (EPT) outcomes, Total IgE (tIgE), sIgE, sIgG4, a positive basophil activation test (BAT) outcome, cytokines, and the fecal biomarkers calprotectin and eosinophil-derived neurotoxin (EDN). A positive SPT outcome and sIgE were biomarkers in egg, milk, and peanut allergy studies. A positive BAT outcome was described as a biomarker in both milk and peanut allergy studies. Egg allergies were tested using tIgE, sIgG4, and the ratio between them. A study on egg allergies described cytokine expression and fecal biomarkers, whereas a study on milk allergies described EPT outcomes.

Among the six peanut studies included, the major determinants of persistence and the severity of peanut allergy were positive BAT and SPT outcomes, as well as sIgE and IgG4. The BAT accurately predicted severe allergic reactions in children with peanut allergies. Higher proportions of activated basophils were associated with more severe reactions during peanut OFC. The BAT results could estimate the severity and threshold of peanut-induced allergic reactions; a high CD63 ratio led to a higher risk of life-threatening reactions in three studies, one of which included adult patients.26-28 An SPT result of ≥ 8 mm in children indicated a high risk of a reaction during OFC.26 Specific IgE cutoffs can also predict the persistence of peanut allergies. The combination of SPT and sIgE could predict the outcomes of oral food challenges, thereby indicating the persistence and severity of allergic reactions.29,30 One study applied a bioinformatics approach to access results from peptide microarray immunoassays aimed at identifying children with peanut allergies. The authors found that a combination of the peptide biomarkers Ara h 2_10, Ara h 2_16, and Ara h 2_18 could differentiate between peanut-allergic and -tolerant groups.31

Previous anaphylaxis was a risk factor for milk allergy persistence in children aged < 6 years32. SPT results were related to the persistence of allergy.30 High levels of milk sIgE were involved in the persistence of milk allergies in children who underwent an OFC.30,32,33 One study identified EPT as a more useful test than SPT and defined EPT as a marker for selecting children at high risk of developing anaphylaxis during food challenges.34 Cytokine IL-13 and IL-10 levels and fecal biomarkers were related to milk allergy persistence;35 additionally, BAT outcomes were associated with more severe clinical milk reactivity, as we found in egg and milk studies.36

A total of 230 OFCs were described in the included studies of egg allergies. The SPT and sIgE cutoffs might predict a positive food challenge and play important roles in the persistence of egg allergies.30 The sIgE;sIgG4 ratios to both ovalbumin (OVA) or ovomucoid (OVM) were higher in 107 children who were reactive to eggs than in those who could tolerate baked eggs.37 Among 95 children with egg allergies who underwent a DBPCFC, a high OVA-sIgE/total IgE ratio predicted the development of tolerance to raw eggs and was superior to sIgE or a positive SPT outcome alone.38 The SPT nullified by hard-boiling eggs or sensitization to egg fractions (low egg white [EW]: egg yolk [EY] sIgE ratio), was associated with baked egg tolerance in a group of children.39 Levels of the cytokines IL-13 and IL-10 were higher among children with FAs who were orally challenged with both egg and milk. Fecal biomarkers such as calprotectin and eosinophil-derived neurotoxin (EDN) were also associated with persistent egg allergies in the same study.35

Discussion

Assays of serum sIgE against specific allergen components or peptides in vitro are the most frequently applied means of diagnosing FAs. However, they are influenced by tIgE levels and potentially different diagnostic cutoff values among studies.40,41 The benefits of tIgE and sIgE levels have been assessed as sIgE:tIgE or sIgE:sIgG4 ratios to enhance the diagnostic and prognostic performance of sIgE. Serum sIgE and sIgE:sIgG4 ratios have assumed an important role in FA natural history and also in predicting immunotherapy response.42 In fact, nine of the 14 selected studies evaluated sIgE, tIgE, and/or sIgG4 for eggs, milk, and/or peanuts, and found that the isolated dosage and ratio between these markers were helpful to predict FA tolerance.29-33,36-39

Egg white and its four allergens (OVM, OVA, ovotransferrin, and lysozyme) are assumed to be the underlying causes of allergic reactions. The selected studies associated high levels of sIgE with egg allergy persistence. These values are important to correlate with tIgE and IgG4, since OVA-sIGE:tIgE predicted tolerance (OVA-sIgE:tIgE) and OVA and OVM-sIgE:IgG4 predicted severity, including anaphylactic reactions.37,38 Brossard et al confirmed the importance of EW over EY fractions, indicating that a high EW/EY ratio could be a marker of egg allergy persistence.39 Although these studies differed in terms of populations and Ig ratios, OVA and OVM are the most studied egg allergens with a direct association between high levels and FA persistence.

Cutoffs for SPT and sIgE have been extensively investigated, and they vary among studies. Two studies proposed that positive SPT outcomes and/or sIgE values are highly predictive of a positive egg, milk, and peanut OFC.29,30 These values can predict the dose above which an OFC outcome might be positive. Although these values could indicate allergy persistence, practical cutoffs are difficult to define, as they depend on many factors, such as patient populations, study protocols, and sample sizes.29,30

The SPT is a safe and highly sensitive method of detecting sIgE to a defined allergen. It is the most inexpensive, popular, and simplest way to evaluate IgE sensitization in vivo.40 Some articles described a high SPT value as a biomarker of FA tolerance or persistence.26,30,37,39 Although high SPT values are described in these reports as being highly predictive of a positive OFC for eggs, milk, and peanuts, the relationship between SPT and OFC outcomes remains controversial. Larger SPT wheels can be related to a positive OFC outcome, but it is not always associated with the severity of allergic reactions.26,30,37,39

The BAT is a functional assay that detects the capacity of IgE to mediate basophil activation after allergen stimulation.43 Basophils express higher levels of their activation markers, CD63 and CD203c in patients with allergies. BAT has acquired a sustained role in distinguishing allergic patients from those who are sensitized but clinically tolerant.42 Four of the selected studies considered BAT outcomes as a biomarker of severity and/or threshold of milk or peanut allergic reactions, and children underwent OFCs to evaluate their responses and degrees of reactions.26-28,36 Santos et al describe a study of 468 children.27 The BAT outcome was an important predictor of the threshold dose of allergic reactions to peanuts during OFCs and accurately identified those who were likely to develop severe or life-threatening reactions during peanut OFC. The optimal cutoff for the BAT outcomes had high sensitivity and specificity for identifying children at high risk of severe peanut allergy reactions.27 Thus, BAT is a biomarker for the severity and threshold of allergic reactions, especially to peanuts according to the studies analyzed here, and should be considered according to clinical history and other risk factors.

Interleukin-10 plays an important role in FA tolerance and is associated with the persistence of milk allergies involved in tolerance induction.44-48 Only one study, performed by Winberg et al, evaluated cytokines as FA biomarkers and showed that a combination of increased numbers of peripheral blood mononuclear cells, IL-13 and IL-10 mRNAs, and fecal calprotectin and EDN are associated with the persistence of allergies to eggs and milk in children.35

Among the 14 included studies, only one presented a high risk of bias according to the NOS (Table 1).33 However, the studies differed in terms of methodological diversity and the variety of studied biomarkers. The BAT, cytokine dosages, and fecal biomarkers are still not routinely accessible. This could explain why the most studied biomarkers were SPT and sIgE, which are the most easily accessible and inexpensive.

Considering the recent increase in FA prevalence and the severity of the reactions, identifying biomarkers of persistence and severity allows patients to avoid the possibility of a harmful event occurring during an OFC. A few studies have identified possible prognostic indicators of persistence or the severity of FA and outcomes during an OFC or a DBPFC. Among the included reports, SPT and sIgE were the most studied biomarkers of FA, and BAT was notably an important biomarker of peanut allergies. Cytokine dosage and fecal biomarkers were evaluated in only one study.

Further investigation is required to identify more accessible biomarkers that could determine the likelihood of having a severe food allergic reaction, thereby preventing the ingestion of food and unnecessary OFCs.

References
[1]
M. Abril-Gil, A. Garcia-Just, F.J. Pérez-Cano, À. Franch, M. Castell.
Development and characterization of an effective food allergy model in Brown Norway rats.
PLoS One, 10 (2015),
[2]
W. Yu, D.M. Freeland, K.C. Nadeau.
Food allergy: immune mechanisms, diagnosis and immunotherapy.
Nat Rev Immunol, 16 (2016), pp. 751-765
[3]
J.H. van Bilsen, L. Verschuren, L. Wagenaar, M.M. Vonk, B.C. van Esch, L.M. Knippels, et al.
A network-based approach for identifying suitable biomarkers for oral immunotherapy of food allergy.
BMC Bioinformatics, 20 (2019), pp. 206
[4]
M.L. Tang, R.J. Mullins.
Food allergy: is prevalence increasing?.
Intern Med J, 47 (2017), pp. 256-261
[5]
C. Escudero, P. Rodríguez Del Río, S. Sánchez-García, I. Pérez-Rangel, N. Pérez-Farinós, C. García-Fernández, et al.
Early sustained unresponsiveness after short-course egg oral immunotherapy: a randomized controlled study in egg-allergic children.
Clin Exp Allergy, 45 (2015), pp. 1833-1843
[6]
A. Muraro, S. Halken, S.H. Arshad, K. Beyer, A.E. Dubois, G. Du Toit, et al.
EAACI food allergy and anaphylaxis guidelines. Primary prevention of food allergy.
Allergy, 69 (2014), pp. 590-601
[7]
NIAID-Sponsored Expert Panel, Boyce JA, A. Assa'ad, A.W. Burks, S.M. Jones, H.A. Sampson, et al.
Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel.
J Allergy Clin Immunol, 126 (2010), pp. S1-58
[8]
T. Umasunthar, J. Leonardi-Bee, M. Hodes, P.J. Turner, C. Gore, P. Habibi, et al.
Incidence of fatal food anaphylaxis in people with food allergy: a systematic review and meta-analysis.
Clin Exp Allergy, 43 (2013), pp. 1333-1341
[9]
O.I. Iweala, S.K. Choudhary, SP. Commins.
Food Allergy.
Curr Gastroenterol Rep, 20 (2018), pp. 17
[10]
S.H. Sicherer, H.A. Sampson.
Food allergy: a review and update on epidemiology, pathogenesis, diagnosis, prevention, and management.
J Allergy Clin Immunol, 141 (2018), pp. 41-58
[11]
D. de Silva, S. Halken, C. Singh, A. Muraro, E. Angier, S. Arasi, et al.
Preventing food allergy in infancy and childhood: systematic review of randomised controlled trials.
Pediatr Allergy Immunol, 31 (2020), pp. 813-826
[12]
V. Verhasselt, J. Genuneit, J.R. Metcalfe, M.K. Tulic, A. Rekima, D.J. Palmer, et al.
Ovalbumin in breastmilk is associated with a decreased risk of IgE-mediated egg allergy in children.
Allergy, 75 (2020), pp. 1463-1466
[13]
V. Verhasselt, V. Milcent, J. Cazareth, A. Kanda, S. Fleury, D. Dombrowicz, et al.
Breast milk-mediated transfer of an antigen induces tolerance and protection from allergic asthma.
Nat Med, 14 (2008), pp. 170-175
[14]
M. Ponce, S.C. Diesner, Z. Szépfalusi, T. Eiwegger.
Markers of tolerance development to food allergens.
Allergy, 71 (2016), pp. 1393-1404
[15]
U. Nurmatov, S. Dhami, S. Arasi, G.B. Pajno, M. Fernandez-Rivas, A. Muraro, et al.
Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis.
Allergy, 72 (2017), pp. 1133-1147
[16]
A. Muraro, T. Werfel, K. Hoffmann-Sommergruber, G. Roberts, K. Beyer, C. Bindslev-Jensen, et al.
EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy.
Allergy, 69 (2014), pp. 1008-1025
[17]
A. Muraro, S. Arasi.
Biomarkers in food allergy.
Curr Allergy Asthma Rep, 18 (2018), pp. 64
[18]
A. Deschildre, S. Lejeune, M. Cap, S. Flammarion, L. Jouannic, F. Amat, J. Just.
Food allergy phenotypes: the key to personalized therapy.
Clin Exp Allergy, 47 (2017), pp. 1125-1137
[19]
J.M. Spergel, M. Boguniewicz, L. Schneider, J.M. Hanifin, A.S. Paller, L.F. Eichenfield.
Food allergy in infants with atopic dermatitis: limitations of food-specific IgE measurements.
Pediatrics, 136 (2015), pp. e1530-e1538
[20]
B. Cuomo, G.C. Indirli, A. Bianchi, S. Arasi, D. Caimmi, A. Dondi, et al.
Specific IgE and skin prick tests to diagnose allergy to fresh and baked cow's milk according to age: a systematic review.
Ital J Pediatr, 43 (2017), pp. 93
[21]
J. Flores Kim, N. McCleary, B.I. Nwaru, A. Stoddart, A Sheikh.
Diagnostic accuracy, risk assessment, and cost-effectiveness of component-resolved diagnostics for food allergy: a systematic review.
Allergy, 73 (2018), pp. 1609-1621
[22]
S. Arasi, M. Mennini, R. Valluzzi, C. Riccardi, A. Fiocchi.
Precision medicine in food allergy.
Curr Opin Allergy Clin Immunol, 18 (2018), pp. 438-443
[23]
K.A. Peeters, R.J. Lamers, A.H. Penninks, E.F. Knol, C.A. Bruijnzeel-Koomen, J.H. van Nesselrooij, et al.
A search for biomarkers as diagnostic tools for food allergy: a pilot study in peanut-allergic patients.
Int Arch Allergy Immunol, 155 (2011), pp. 23-30
[24]
D. Moher, A. Liberati, J. Tetzlaff, D.G. Altman, PRISMA Group.
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
PLoS Med, 6 (2009),
[25]
J.P. Higgins, J. Thomas, J. Chandler, M. Cumpston, T. Li, M.J. Page, et al.
Cochrane handbook for systematic reviews of interventions version 6.2  (updated February 2021).
[26]
A.F. Santos, G. Du Toit, C. O'Rourke, N. Becares, N. Couto-Francisco, S. Radulovic, et al.
Biomarkers of severity and threshold of allergic reactions during oral peanut challenges.
J Allergy Clin Immunol, 146 (2020), pp. 344-355
[27]
A.F. Santos, G. Du Toit, A. Douiri, S. Radulovic, A. Stephens, V. Turcanu, et al.
Distinct parameters of the basophil activation test reflect the severity and threshold of allergic reactions to peanut.
J Allergy Clin Immunol, 135 (2015), pp. 179-186
[28]
R.S. Chinthrajah, N. Purington, S. Andorf, J.S. Rosa, K. Mukai, R. Hamilton, et al.
Development of a tool predicting severity of allergic reaction during peanut challenge.
Ann Allergy Asthma Immunol, 121 (2018), pp. 69-76
[29]
N.H. van Nieuwaal, W. Lasfar, Y. Meijer, P.A. Kentie, A.E. Flinterman, S.G. Pasmans, et al.
Utility of peanut-specific IgE levels in predicting the outcome of double-blind, placebo-controlled food challenges.
J Allergy Clin Immunol, 125 (2010), pp. 1391-1392
[30]
S. Sindher, A.J. Long, N. Purington, M. Chollet, S. Slatkin, S. Andorf, et al.
Analysis of a large standardized food challenge data set to determine predictors of positive outcome across multiple allergens.
Front Immunol, 9 (2018), pp. 2689
[31]
J. Lin, F.M. Bruni, Z. Fu, J. Maloney, L. Bardina, A.L. Boner, et al.
A bioinformatics approach to identify patients with symptomatic peanut allergy using peptide microarray immunoassay.
J Allergy Clin Immunol, 129 (2012), pp. 1321-1328
[32]
Y. Koike, S. Sato, N. Yanagida, T. Asaumi, K. Ogura, K. Ohtani, et al.
Predictors of persistent milk allergy in children: a retrospective cohort study.
Int Arch Allergy Immunol, 175 (2018), pp. 177-180
[33]
B. Ahrens, L.C. Lopes de Oliveira, L. Grabenhenrich, G. Schulz, B. Niggemann, U. Wahn, et al.
Individual cow's milk allergens as prognostic markers for tolerance development?.
Clin Exp Allergy, 42 (2012), pp. 1630-1637
[34]
F. Bellini, G. Ricci, D. Remondini, A. Pession.
Cow's milk allergy (CMA) in children: identification of allergologic tests predictive of food allergy.
Eur Ann Allergy Clin Immunol, 46 (2014), pp. 100-105
[35]
A. Winberg, O. Nagaeva, I. Nagaev, C. Lundell, I. Arencibia, L. Mincheva-Nilsson, et al.
Dynamics of cytokine mRNA expression and fecal biomarkers in school-children undergoing a double-blind placebo-controlled food challenge series.
Cytokine, 88 (2016), pp. 259-266
[36]
L.S. Ford, K.A. Bloom, A.H. Nowak-Węgrzyn, W.G. Shreffler, M. Masilamani, H.A. Sampson.
Basophil reactivity, wheal size, and immunoglobulin levels distinguish degrees of cow's milk tolerance.
J Allergy Clin Immunol, 131 (2013), pp. 180-186
[37]
J.C. Caubet, R. Bencharitiwong, E. Moshier, J.H. Godbold, H.A. Sampson, A. Nowak-Węgrzyn.
Significance of ovomucoid- and ovalbumin-specific IgE/IgG(4) ratios in egg allergy.
J Allergy Clin Immunol, 129 (2012), pp. 739-747
[38]
M. Vazquez-Ortiz, A. Machinena-Spera, M.T. Giner, M. Alvaro, M. Piquer, O. Dominguez, et al.
Ovalbumin-specific IgE/total IgE ratio improves the prediction of tolerance development in egg-allergic children aged ≥5 years.
Pediatr Allergy Immunol, 26 (2015), pp. 580-583
[39]
C. Brossard, F. Rancé, M. Drouet, E. Paty, A. Juchet, C. Guérin-Dubiard, et al.
Relative reactivity to egg white and yolk or change upon heating as markers for baked egg tolerance.
Pediatr Allergy Immunol, 30 (2019), pp. 225-233
[40]
I.J. Ansotegui, G. Melioli, G.W. Canonica, L. Caraballo, E. Villa, M. Ebisawa, et al.
IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper.
World Allergy Organ J, 13 (2020),
[41]
T.J. Federly, B.L. Jones, H. Dai, C. Dinakar.
Interpretation of food specific immunoglobulin E levels in the context of total IgE.
Ann Allergy Asthma Immunol, 111 (2013), pp. 20-24
[42]
S. Passanisi, F. Lombardo, G. Crisafulli, G. Salzano, T. Aversa, G.B. Pajno.
Novel diagnostic techniques and therapeutic strategies for IgE-mediated food allergy.
Allergy Asthma Proc, 42 (2021), pp. 124-130
[43]
O. Hemmings, M. Kwok, R. McKendry, A.F. Santos.
Basophil activation test: old and new applications in allergy.
Curr Allergy Asthma Rep, 18 (2018), pp. 77
[44]
C.E. West, M.C. Jenmalm, S.L. Prescott.
The gut microbiota and its role in the development of allergic disease: a wider perspective.
Clin Exp Allergy, 45 (2015), pp. 43-53
[45]
M.M. Tiemessen, A.G. Van Ieperen-Van Dijk, C.A. Bruijnzeel-Koomen, J. Garssen, E.F. Knol, E. Van Hoffen.
Cow's milk-specific T-cell reactivity of children with and without persistent cow's milk allergy: key role for IL-10.
J Allergy Clin Immunol, 113 (2004), pp. 932-939
[46]
M. Battaglia, C. Gianfrani, S. Gregori, M.G. Roncarolo.
IL-10-producing T regulatory type 1 cells and oral tolerance.
Ann N Y Acad Sci, 1029 (2004), pp. 142-153
[47]
C.M. Jacob, A.C. Pastorino, T.S. Okay, A.P. Castro, A.K. Gushken, L.A. Watanabe, et al.
Interleukin 10 (IL10) and transforming growth factor β1 (TGFβ1) gene polymorphisms in persistent IgE-mediated cow's milk allergy.
Clinics (Sao Paulo), 68 (2013), pp. 1004-1009
[48]
E.F. Knol, N.W. de Jong, L.H. Ulfman, M.M. Tiemessen.
Management of cow's milk allergy from an immunological perspective: what are the options?.
Nutrients, 11 (2019), pp. 2734
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