R. J. B. Klemans

The diagnostic value of specific IgE to Ara h 2 to predict peanut allergy in children is comparable to a validated and updated diagnostic prediction model.

BACKGROUND A diagnostic prediction model for peanut allergy in children was recently published, using 6 predictors: sex, age, history, skin prick test, peanut specific immunoglobulin E (sIgE), and total IgE minus peanut sIgE. OBJECTIVES To validate this model and update it by adding allergic rhinitis, atopic dermatitis, and sIgE to peanut components Ara h 1, 2, 3, and 8 as candidate predictors. To develop a new model based only on sIgE to peanut components. METHODS Validation was performed by testing discrimination (diagnostic value) with an area under the receiver operating characteristic curve and calibration (agreement between predicted and observed frequencies of peanut allergy) with the Hosmer-Lemeshow test and a calibration plot. The performance of the (updated) models was similarly analyzed. RESULTS Validation of the model in 100 patients showed good discrimination (88%) but poor calibration (P < .001). In the updating process, age, history, and additional candidate predictors did not significantly increase discrimination, being 94%, and leaving only 4 predictors of the original model: sex, skin prick test, peanut sIgE, and total IgE minus sIgE. When building a model with sIgE to peanut components, Ara h 2 was the only predictor, with a discriminative ability of 90%. Cutoff values with 100% positive and negative predictive values could be calculated for both the updated model and sIgE to Ara h 2. In this way, the outcome of the food challenge could be predicted with 100% accuracy in 59% (updated model) and 50% (Ara h 2) of the patients. CONCLUSIONS Discrimination of the validated model was good; however, calibration was poor. The discriminative ability of Ara h 2 was almost comparable to that of the updated model, containing 4 predictors. With both models, the need for peanut challenges could be reduced by at least 50%.

Diagnostic accuracy of specific IgE to components in diagnosing peanut allergy: a systematic review

The diagnostic accuracy of skin prick test (SPT) and specific IgE (sIgE) to peanut extract in diagnosing peanut allergy is suboptimal. Recent studies have evaluated sIgE to peanut components as a possible new diagnostic tool. The aim of our review was to systematically search the literature to assess the diagnostic value of sIgE to peanut components in diagnosing peanut allergy. A literature search was performed in PubMed, Embase and the Cochrane Library. Results were subsequently screened for in‐ and exclusion criteria. The quality of eligible studies was assessed using a standardized quality assessment tool (QUADAS‐2). Data on sensitivity, specificity, and positive and negative likelihood ratios were extracted or calculated for a descriptive analysis. Twenty‐two studies were eligible, of which 21 studies in paediatric populations. Most studies reported on sIgE to peanut extract (15) and sIgE to Ara h 2 (12), followed by SPT (9) and sIgE to Ara h 1 (7). All studies were at risk of bias or caused applicability concerns on at least one item of the quality assessment tool. The best combination of diagnostic accuracy measures of all diagnostic tests was found for sIgE to Ara h 2. This finding was independent of geographical location. Compared to SPT and sIgE to peanut extract, sIgE to Ara h 2 was mainly superior in diagnosing peanut allergy in case of a positive test result. Worst diagnostic accuracy measures were found in general for sIgE to Ara h 8 and sIgE to Ara h 9. sIgE to Ara h 2 showed the best diagnostic accuracy of all diagnostic tests to diagnose peanut allergy. Compared to the currently used SPT and sIgE to peanut extract, sIgE to Ara h 2 was superior in diagnosing peanut allergy and should therefore replace these tests in daily clinical practice, especially in children.

Ara h 2 is the best predictor for peanut allergy in adults

BACKGROUND Specific IgE (sIgE) to Ara h 2 as a clinical predictor for peanut allergy in children has a diagnostic value comparable with a prediction model that contains sex, skin prick test (SPT), sIgE to peanut extract, and total IgE minus sIgE. In adults, the diagnostic value of peanut components has not yet been studied. OBJECTIVE To validate a pediatric prediction model in an adult population; to define the diagnostic value of sIgE to peanut components. METHODS Validation was performed by discrimination with an area under the receiver operating characteristic curve (AUC) and calibration with the Hosmer-Lemeshow test. The diagnostic value of the peanut components was assessed with the AUC. RESULTS Validation of the pediatric model in 94 adults showed poor discrimination (AUC, 0.64) but good calibration (P = .48); sIgE to Ara h 2 was the best diagnostic predictor (AUC, 0.76). By using a cutoff value with a 100% positive predictive value (≥1.75 kU/L), 28% of patients could be diagnosed with 100% accuracy. The highest negative predictive value was 63%. A higher negative predictive value could not be calculated for any other test. Although sIgE to Ara h 2 was significantly correlated with severity, it did not discriminate between mild and severe allergy in individual patients (AUC < 0.65). CONCLUSION sIgE to Ara h 2 has the best discriminative ability of all diagnostic tests. It can accurately diagnose peanut allergy in 28% of patients but cannot be used to exclude a peanut allergy in an adult population.

The diagnostic accuracy of specific IgE to Ara h 6 in adults is as good as Ara h 2

Specific IgE (sIgE) to Ara h 2 is useful in diagnosing peanut allergy. Our aim was to assess the diagnostic value of sIgE to Ara h 6, another 2S albumin, in an adult population suspected of peanut allergy. Subjects with suspected peanut allergy between 2002 and 2013 were included if a diagnostic double‐blind, placebo‐controlled food challenge with peanut was performed. sIgE to Ara h 2 and Ara h 6 was measured by ImmunoCAP ISAC 112. Of 107 challenged subjects, 65 had a positive challenge (61%). The discriminative ability of sIgE to Ara h 2 and Ara h 6 was comparable: AUC 0.81 vs 0.82. Positive predictive value for both tests was 95% using a cutoff value ≥1 ISU/l with poor corresponding sensitivity values (58% for Ara h 2, 62% for Ara h 6), but good specificity values (95% for both tests). In conclusion, the diagnostic value of sIgE to Ara h 6 on population level was as good as sIgE to Ara h 2. On individual level, however, 5% of the subjects showed contradicting results between both tests using a cutoff of 0.3 ISU/l, leading to a risk of misdiagnosis if only one of both tests is used.

Components in soy allergy diagnostics: Gly m 2S albumin has the best diagnostic value in adults

Thus far, four soy allergens have been characterized. Their diagnostic value was assessed only using a case‐control design with controls not suspected of soy allergy or in a soy‐allergic population without controls. Our objective was to analyze the diagnostic value of specific immunoglobulin E (sIgE) to Gly m 2S albumin, Gly m 4, 5, and 6, and their possible relation with severity or culprit soy product.

IgE binding to peanut components by four different techniques: Ara h 2 is the most relevant in peanut allergic children and adults

Several studies have analysed the diagnostic value of specific IgE (sIgE) for individual peanut allergens. However, little is known about the concordance between different techniques available in both children and adults.

Specific IgE to Jug r 1 has no additional value compared with extract-based testing in diagnosing walnut allergy in adults

To the Editor: Three English walnut (Juglans regia) components are currently commercially available for specific IgE (sIgE) testing: a 2S albumin (Jug r 1), a vicilin-like 7S globulin (Jug r 2), and a lipid transfer protein (Jug r 3). Their value in diagnosing walnut allergy remains unknown. The aim of this study was to prospectively investigate the predictive value of sIgE to walnut components Jug r 1, Jug r 2, and Jug r 3 in subjects suspected of walnut allergy and to compare the results with skin prick test (SPT) and sIgE to walnut extract. In addition, their ability to predict the severity of walnut allergy was assessed. Adult subjects (n 5 66) with a suspected walnut allergy were included between November 2012 and October 2015. Diagnostic tests included SPT with 3 commercial walnut extracts (ALK-Abell o [Hørsholm, Denmark], Stallergenes [Antony, France], and GREER [Lenoir, NC]), sIgE detection on ImmunoCAP (walnut extract, Jug r 1 and Jug r 3, hereafter called CAP), and ImmunoCAP ISAC (Jug r 1, Jug r 2, and Jug r 3, hereafter called ISAC). A double-blind placebo-controlled food challenge with raw walnut was performed to establish walnut allergy or tolerance. The local ethics committee gave ethical approval. Detailed methods are reported in theMethods section in this article’s Online Repository at www.jacionline.org. Walnut allergy was confirmed in 33 of 55 challenged subjects (60%) (for study flow chart, see Fig E1 in this article’s Online Repository at www.jacionline.org). Median age of all subjects was 32 years (interquartile range, 25-38 years) and 22% were men. Age and sex distribution did not differ between the included and excluded subjects. Subject characteristics are listed in Table E1 in this article’s Online Repository at www.jacionline.org. Sensitization to Jug r 1 (2S albumin) was most prevalent, with more than half of the walnut-allergic subjects demonstrating sIgE on both CAP and ISAC. Sensitization results are listed in Table I. All subjects sensitized to Jug r 2 were also cosensitized

The degree of whey hydrolysis does not uniformly affect in vitro basophil and T cell responses of cow's milk-allergic patients

Several studies investigated whether hydrolysed proteins can induce tolerance to cows milk (CM) in children at risk of developing CM allergy. Due to methodological problems and inconsistent findings, the evidence for a tolerogenic effect is limited. A major problem is that different hydrolysates may give different outcomes due to variations in their production and composition.

Objective eliciting doses of peanut‐allergic adults and children can be combined for risk assessment purposes

To improve food labelling strategies, information regarding eliciting doses (EDs) and the effect of patient characteristics on these EDs is necessary.

Threshold Dose Distribution in Walnut Allergy

BACKGROUND In food allergy, eliciting doses (EDs) of foods on a population level can improve risk management and labeling strategies for the food industry and regulatory authorities. Previously, data available for walnut were unsuitable to determine EDs. OBJECTIVE The objective of this study was to determine EDs for walnut allergic adults and to compare with previously established threshold data for peanut and tree nuts. METHODS Prospectively, adult subjects with a suspected walnut allergy underwent a low-dose double-blind, placebo-controlled food challenge. Individual no observed and lowest observed adverse effect levels were determined and log-normal, log-logistic, and Weibull models were fit to the data. Estimated ED values were calculated for the ED5, ED10, and ED50, the dose respectively predicted to provoke an allergic reaction in 5%, 10%, and 50% of the walnut allergic population. RESULTS Fifty-seven subjects were challenged and 33 subjects were confirmed to be walnut allergic. Objective symptoms occurred in 20 of the positive challenges (61%). The cumulative EDs in the distribution models ranged from 3.1 to 4.1 mg for the ED05, from 10.6 to 14.6 mg walnut protein for the ED10, and from 590 to 625 mg of walnut protein for the ED50. CONCLUSIONS Our data indicate that population EDs for walnut are slightly higher compared with those for peanut and hazelnut allergy. Currently available data indicate that the ED values for hazelnut could be used as a conservative temporary placeholder when implementing risk management strategies for other tree nuts where little or no food challenge data are available.