C.F. den Hartog Jager

Children with peanut allergy recognize predominantly Ara h2 and Ara h6, which remains stable over time

Background In peanut‐allergic adults, IgE is mainly directed to Ara h1 and Ara h2. More recently, a role for Ara h6 has been suggested. In contrast to adults, IgE in children can fluctuate over time. Therefore, children may have a more dynamic reactivity to peanut.

Does skin prick test reactivity to purified allergens correlate with clinical severity of peanut allergy

Background Recognition of specific peanut allergens or the diversity of IgE binding to peanut allergens may play a role in the elicitation of severe allergic reactions.

T cell responses to major peanut allergens in children with and without peanut allergy

Background T cell responses involved in peanut allergy are poorly understood.

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.

Chemical modification of peanut conglutin reduces IgE reactivity but not T cell reactivity in peanut‐allergic patients

Specific immunotherapy for peanut allergy is associated with significant side‐effects. Chemically modified allergens may provide a safer alternative.

2S protein Ara h 7.0201 has unique epitopes compared to other Ara h 7 isoforms and is comparable to 2S proteins Ara h 2 and 6 in basophil degranulation capacity

Screening for specific IgE against 2S albumin proteins Ara h 2 and 6 has good positive predictive value in diagnosing peanut allergy. From the third 2S member Ara h 7, 3 isoforms have been identified. Their allergenicity has not been elucidated.

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.

Major hazelnut and peanut allergens are potent in basophil activation and cross-react at T-cell level

To the Editor, Sensitization to hazelnut and peanut has already been shown early in life, before introduction of hazelnut and peanut into the diet. Cross-reactions between structurally related proteins in hazelnut and peanut may play a role in this pattern of concomitant sensitization. Cross-reactions may be induced at IgE and T-cell level. A previous paper by our group showed limited cross-reactivity between seed storage proteins in hazelnut and peanut at IgE level. The aim of this study was to assess the potency of the response to hazelnut and peanut allergens in basophil activation and at T-cell level in a hazelnut allergic population with or without additional peanut allergy and to evaluate potential T-cell cross-reactivity between hazelnut and peanut. Nineteen patients (12 children and 7 adults) with objective symptoms to hazelnut in DBPCFC or by history were selected from a cohort of 161 patients with a sensitization to hazelnut extract (Tables S1,S2 and Data S1). The basophil activation test was performed with passively sensitized basophils in a subset of 11 patients with high levels of sensitization to the different hazelnut allergens (Data S1). Five of these patients also had a peanut allergy with objective symptoms (Table S1). In the 11 patients, IgE to hazelnut extract was significantly higher than to different purified hazelnut and peanut allergens, peanut, and birch pollen extract and rBet v 1. IgE to rCor a 14 was significantly higher than IgE to nCor a 9 (P < .01), while IgE to rCor a 1 was not significantly different from IgE to nCor a 9 or rCor a 14 (Table S2). Basophil activation (CD-sens: Figure 1) showed that the 2S albumin rCor a 14 was the most potent hazelnut allergen, followed by the PR-10 protein rCor a 1 (P = .08) and the 11S globulin nCor a 9 (P = .02). In two patients with higher IgE levels to Cor a 9 than to Cor a 14 (HN011C and HN135C), Cor a 14 was still more potent in basophil activation (data not shown), suggesting that Cor a 14 is intrinsically more potent in basophil activation. This pattern was equivalent to that of peanut allergens, for which the 2S albumins in peanut Ara h 2 and Ara h 6 were the most potent. The strong potency of 2S albumins in basophil activation further confirms the relevance of IgE to Cor a 14 or Ara h 2 in the diagnostic workup of hazelnut and peanut allergy. The basophil response to hazelnut and peanut extract and their purified allergens in individuals with an objective allergy to both hazelnut and peanut was comparable (data not shown). The potency of allergens in basophil activation correlated positively with the IgE levels (data not shown). In contrast to IgE responses, T-cell responses are more difficult to study. As only a small fraction of the CD4+ T-cell pool is allergen-specific, T-cell responses were studied in allergen-specific T-cell lines (TCLs). Sixteen hazelnutand 9 peanut-specific TCLs were generated from PBMCs from 16 patients with a hazelnut allergy with objective symptoms (Table S1). TCLs with a proliferative response to hazelnut extract with an SI ≥ 2.0 were selected. The majority of hazelnutand peanut-specific TCLs showed a significant proliferation to both hazelnut and peanut extract, as well as their major allergens (Figure 2A,B). Upon stimulation, hazelnutand peanut-specific TCLs produced mainly IL-13 and IFN-c, and limited amounts of IL-10 (Figure 2C). The TCLs were specific, as evidenced by their unresponsiveness to casein, an unrelated cow’s milk allergen (data not shown). The magnitude of the response to purified hazelnut and peanut allergens was significantly lower than to hazelnut and peanut extract (Figure 2A,B). Cross-reactivity at T-cell level between hazelnut and peanut has been described previously in five patients, partially driven by Ara h 1 or Ara h 2. We performed an additional characterization of the component in hazelnut extract causing strong T-cell proliferation. To identify the component causing the strong T-cell proliferation in hazelnut extract, individual major allergens were tested. Cor a 1, Cor a 9 and Cor a 14 could be excluded based on

Sensitization to Cor a 9 and Cor a 14 is highly specific for a severe hazelnut allergy in Dutch children and adults

Background Component-resolved diagnosis has been shown to improve diagnosis of food allergy. The aim of this study was to evaluate whether component-resolved diagnosis may help to identify patients at risk of severe allergic reactions to hazelnut. Methods A total of 161 hazelnut-sensitized patients were included: 40 children and 15 adults with objective symptoms in DBPCFC and 24 adults with a convincing severe history were compared to 41 children and 41 adults with no or subjective symptoms in DBPCFC (grouped together). IgE levels to hazelnut extract and single components were analyzed with ImmunoCAP.