Predictive values of component-specific IgE for the outcome of peanut and hazelnut food challenges in children

Beyer, Kirsten; Grabenhenrich, Linus; Härtl, Magdalena; Beder, Alena; Kalb, Birgit; Ziegert, Mandy; Finger, Antje; Harandi, Neda; Schlags, Rupert; Gappa, Monika; Puzzo, Letizia; Röblitz, Holger; Millner-Uhlemann, Martina; Büsing, Susanne; Ott, Hagen; Lange, Lars; Niggemann, B.

doi:10.1111/all.12530

Cited by 178 publications

(205 citation statements)

References 20 publications

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“…In contrast, none of the sensitized but peanut-asymptomatic subjects demonstrated specific IgE reactivity to the peanut seed storage proteins Ara h 1, Ara h 2, Ara h 3 and Ara h 6, resulting in specificities of 100% for those allergens. In contrast, recent studies have shown that 26% of sensitized but tolerant patients' sera contained IgE specific to Ara h 2 [19], and that a 95% probability of a positive peanut challenge could only be established for sIgE specific to Ara h 2 with a threshold of 42.2 kU A /l and above [20]. We showed that 72% of Austrian peanut-allergic subjects had IgE specific to at least one of those four allergens.…”

Section: Discussionmentioning

confidence: 52%

Component-Resolved IgE Profiles in Austrian Patients with a Convincing History of Peanut Allergy

Ackerbauer

Bublin

Radauer

et al. 2015

Int Arch Allergy Immunol

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Background: Peanut allergy develops after primary sensitization to peanut allergens and/or IgE cross-sensitization with homologous allergens from various plants. Therefore, heterogeneous patterns of sensitization to individual peanut allergens are observed in different countries. The aim of this study was to examine the IgE sensitization patterns of Austrian peanut-allergic patients. Methods: Sera from 65 peanut-allergic patients and 20 peanut-tolerant atopics were obtained in four Austrian allergy clinics.Sensitization patterns against peanut allergens Ara h 1-3, 6, 8 and 9 were identified by ImmunoCAP and ImmunoCAP ISAC. Results: Austrian peanut-allergic patients were sensitized to Ara h 2 and 6 (71%), followed by Ara h 1 (62%), Ara h 8 (45%), Ara h 3 (35%) and Ara h 9 (11%). All sera containing Ara h 2-specific IgE were also positive for Ara h 6, with Ara h 6-specific IgE levels significantly (p < 0.05) higher compared with Ara h 2. Twelve percent displayed IgE reactivity exclusively to Ara h 8. Peanut extract and Ara h 8 showed low diagnostic specificities of 25 and 10%, respectively. The other peanut allergens showed 100% specificity. Diagnostic sensitivities determined by ImmunoCAP ISAC and ImmunoCAP were highly similar for Ara h 2, 3 and 8. Conclusions: Themajority of symptomatic peanut-allergic patients are sensitized to Ara h 2 and Ara h 6. In peanut-symptomatic patients with additional birch pollen allergy, other peanut allergens, especially Ara h 8, should be tested when IgE reactivity to Ara h 2 is absent.

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Section: Discussionmentioning

confidence: 52%

Component-Resolved IgE Profiles in Austrian Patients with a Convincing History of Peanut Allergy

Ackerbauer

Bublin

Radauer

et al. 2015

Int Arch Allergy Immunol

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“…[4] A recent Japanese study has suggested an Ara h 2 cutoff of 4 kU/L to have a 91% PPV for peanut allergy, [16] and in a German study a 90% probability for positive peanut challenge for Ara h 2 was estimated at 14.4 kU/L. [17] In our population, commonly used PPVs for SPT, ImmunoCAP Peanut and Ara h 2 performed suboptimally at 85%, 77% and 73%, respectively. Furthermore, there were significant ethnic differences, with the Xhosa patients faring even more poorly using these cut-offs.…”

Section: Discussionmentioning

confidence: 60%

Which test is best for diagnosing peanut allergy in South African children with atopic dermatitis?

Gray

Levin

2016

S Afr Med J

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Background. Diagnosing peanut allergy based on sensitisation alone leads to an unacceptable rate of overdiagnosis. Objective. To define parameters that may help differentiate peanut allergy from asymptomatic sensitisation in a cohort of South African (SA) children with atopic dermatitis (AD). It is the first study in SA to utilise oral food challenge tests and analyse peanut component patterns.Methods. This was a prospective, observational study at a paediatric university hospital in Cape Town, SA. Children with AD, aged 6 months -10 years, were recruited randomly. They were assessed for sensitisation and allergy to peanut by questionnaire, skin-prick tests (SPTs), immuno solid-phase allergen chip (ISAC) tests, ImmunoCAP component tests to Ara h 1, 2, 3, 8 and 9, and incremental food challenges. Results. One hundred participants (59 Xhosa (black Africans) and 41 of mixed race, median age 42 months) were enrolled. Overall, 44% of patients were peanut sensitised and 25% had a true peanut allergy. SPTs and ImmunoCAP Ara h 2 produced the highest areas under the receiver operating characteristic curve for predicting peanut allergy in peanut-sensitised patients. The ISAC test was less sensitive, more specific and produced significantly lower median values than ImmunoCAP tests. Ara h 2 was the most useful component in differentiating allergy from tolerance in both ethnic groups, being positive in 92% of allergic and 40% of sensitised but tolerant children (p<0.001). There was little additional contribution from Ara h 1 and 3. Ara h 8 and 9 were associated with tolerance. Commonly used 95% positive predictive values (PPVs) for SPTs, peanut-specific IgE and Ara h 2 levels fared suboptimally in our population. Maximum PPVs for this study population were found at SPT 11 mm, peanut IgE 15 kU/L and ImmunoCAP Ara h 2 of 8 kU/L, but these adjusted levels still had suboptimal PPVs in Xhosa subjects. Severe peanut allergy was associated with increased median peanut IgE and Ara h 2. Conclusions. The component Ara h 2 was useful for differentiating allergy from tolerance in both ethnic groups in this SA cohort. Ninetyfive percent PPVs for peanut allergy tests may need to be revised, especially in Xhosa patients. An SPT result ≥11 mm as well as Ara h 2 ≥8 kU/L had the best predictive value for peanut allergy.

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“…Forty to sixty percent of children with milk or egg allergy will outgrow their food allergy until the age of 6 years (100, 101), whereas this occurs at a lower rate in children with allergy to peanut or tree nuts. These individuals may be considered prototypic for tolerance acquisition after established potentially life-threatening food allergy (100,(102)(103)(104)(105). The sequence of events and biomarkers that define individuals with persistent food allergy and those who outgrow their food allergy remain unclear.…”

Section: Oral and Sublingual Immunotherapy In Food Allergymentioning

confidence: 99%

Markers of tolerance development to food allergens

Ponce

Diesner

Szépfalusi

et al. 2016

Allergy

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IgE-mediated reactions to food allergens are the most common cause of anaphylaxis in childhood. Although allergies to cow's milk, egg, or soy proteins, in contrast to peanut and tree nut allergens, resolve within the first 6 years of life in up to 60% due to natural tolerance development, this process is not well understood. At present, there is no cure or treatment for food allergy that would result in an induction of tolerance to the symptom-eliciting food. Avoidance, providing an emergency plan and education, is the standard of treatment. Oral immunotherapeutic approaches have been proven reasonable efficacy; however, they are associated with high rates of side-effects and low numbers of patients achieving tolerance. Nevertheless, mechanisms that take place during oral immunotherapy may help to understand tolerance development. On the basis of these therapeutic interventions, events like loss of basophil activation and induction of regulatory lymphocyte subsets and of blocking antibodies have been described. Their functional importance at a clinical level, however, remains to be investigated in detail. Consequently, there is eminent need to understand the process of tolerance development to food allergens and define biomarkers to develop and monitor new treatment strategies for food allergy.IgE-mediated food allergy represents the most important cause of anaphylaxis in childhood. While milk and egg allergy are associated with a high rate of natural tolerance development within the first 6 years of life, this is less clear for other food allergies. Consequently, once it is communicated the diagnosis persists often lifelong severely impacting the quality of life of the patient and the environment despite the recommendation to reconsider clinical tolerance development from time to time.Currently, avoidance, providing an emergency plan and teaching, is the standard of treatment; however, there is no cure or treatment that has reached the level of recommendation to re-induce tolerance to the symptom-eliciting food. Tolerance assessment occurs either via oral food challenges or due to unintended exposure. Given the cost and time intensiveness of oral food challenges and its potential harmfulness, there is eminent need to understand the process of tolerance development and define markers thereof to develop and monitor new treatment strategies for food allergy. This review aimed to provide an overview on recent advances regarding markers and mechanisms of tolerance development to food allergens.Oral tolerance in the context of food allergy is considered to occur if the antigen/food can be ingested without problems despite prolonged periods of avoidance, while the status of desensitization is strictly dependent on regular ingestion of the respective food in order to confer protection from allergic reactions. Currently, there is no general consensus on the exact time frame of avoidance and re-exposure that would allow the usage of the terminus tolerance that is considered equivalent to cure in the context of or...

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Predictive values of component-specific IgE for the outcome of peanut and hazelnut food challenges in children

Abstract: Ara h 2- and Cor a 14-specific IgE are useful to estimate the probability for a positive challenge outcome in the diagnostic work-up of peanut or hazelnut allergy making some food challenges superfluous.

Cited by 178 publications

References 20 publications

Component-Resolved IgE Profiles in Austrian Patients with a Convincing History of Peanut Allergy

Component-Resolved IgE Profiles in Austrian Patients with a Convincing History of Peanut Allergy

Which test is best for diagnosing peanut allergy in South African children with atopic dermatitis?

Markers of tolerance development to food allergens

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