Mark A. Blankestijn

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.

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

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.

Specific IgE to peanut 2S albumin Ara h 7 has a discriminative ability comparable to Ara h 2 and 6

Little is known on the clinical relevance of peanut 2S albumin Ara h 7.

A subset of walnut allergic adults is sensitized to walnut 11S globulin Jug r 4

The role of sensitization to commercially available allergens of English walnut (Juglans regia) Jug r 1, 2 and 3 in walnut allergy has been previously investigated in walnut allergic adults and was unable to explain all cases of walnut allergy.

Can alternative epitope mapping approaches increase the impact of B-cell epitopes in food allergy diagnostics?

In vitro allergy diagnostics are currently based on the detection of specific IgE binding on intact allergens or a mixture thereof. This approach has drawbacks as it may yield false‐negative and/or false‐positive results. Thus, we reviewed the impact of known B‐cell epitopes of food allergens to predict transience or persistence, tolerance or allergy and the severity of an allergic reaction and to examine new epitope mapping strategies meant to improve serum‐based allergy diagnostics. Recent epitope mapping approaches have been worthwhile in epitope identification and may increase the specificity of allergy diagnostics by using epitopes predominately recognized by allergic patients in some cases. However, these approaches did not lead to discrimination between clinically relevant and irrelevant epitopes so far, since the polyclonal serum IgE‐binding epitope spectrum seems to be too individual, independent of the disease status of the patients. New epitope mapping strategies are necessary to overcome these obstacles. The use of patient‐derived monoclonal antibodies instead of patient sera for functional characterization of clinically relevant and irrelevant epitope combinations, distinguished by their ability to induce degranulation, might be a promising approach to gain more insight into the allergic reaction and to improve serum‐based allergy diagnostics.

Could daratumumab be used to treat severe allergy

In the management of allergic diseases, targeting IgE using biologicals is a current research focus. This proof of concept shows that plasma cell depletion using daratumumab results in decreased total and allergen-specific IgE levels.

Food sensitisation patterns measured by ISAC multiplex assay in the Netherlands

Results Of 943 ISAC tests, 852 showed sensitization to at least one component and were included for further analysis. Mean age was 33,4 years. The majority of patients in our population was poly-sensitized, with 66% recognizing more than ten components. The most recognized component was Bet v 1 (70%). The top 10 food allergens were: apple (Mal d 1; 65%), peach (Pru p 1; 63%), hazelnut (Cor a 1.0401; 63%), peanut (Ara h 8; 56%, Ara h 6; 23%, Ara h 2; 15%), soy (Gly m 4; 39%), celery (Api g 1; 25%), kiwi (Act d 8; 20%) and walnut (Jug r 2; 15%). 84% showed sensitization to one or more food allergens. Within this group, 84% recognized at least one PR-10 component, followed by storage proteins (35%) and non-specific lipid transfer proteins (nsLTP; 12%). The prevalence of sensitization to cross-reactive carbohydrate determinants (CCD) within the entire population was 9%. Sensitization to at least one food components of animal origin (cow’s milk/egg) was seen in 19% of all cases, with Bos d 8 recognized most frequently (8.1%). The ISAC seems to support clinical suspicion of food allergy in most cases, although sensitization together with a negative patient history is common.