Kirsten Skamstrup Hansen

Component-resolved in vitro diagnosis of hazelnut allergy in Europe

BACKGROUND Food allergy to hazelnut occurs both with and without concomitant pollen allergy. OBJECTIVE We sought to evaluate a panel of hazelnut allergens for diagnosis of hazelnut allergy in Spain, Switzerland, and Denmark. METHODS Fifty-two patients with a positive double-blind, placebo-controlled food challenge result with hazelnuts; 5 patients with a history of anaphylaxis; 62 patients with pollen allergy but hazelnut tolerance; and 63 nonatopic control subjects were included. Serum IgE levels to hazelnut extract, recombinant hazelnut allergens (rCor a 1.04, rCor a 2, rCor a 8, rCor a 11), and native allergens (nCor a 9, nCor a Bd8K, nCor a Bd11K) were analyzed by means of ImmunoCAP. RESULTS Among patients with hazelnut allergy, 91% (Switzerland/Spain, 100%; Denmark, 75%) had IgE to hazelnut extract, 75% to rCor a 1.04, 42% to rCor a 2, 28% to rCor a 8, and 2% to rCor a 11. The highest rate of sensitization to Cor a 1.04 was found in the northern regions (Switzerland/Denmark, 100%; Spain, 18%), whereas IgE to the lipid transfer protein rCor a 8 prevailed in Spain (Spain, 71%; Switzerland, 15%; Denmark, 5%). IgE to profilin rCor a 2 was equally distributed (40% to 45%). Among control subjects with pollen allergy, 61% had IgE to hazelnut extract, 69% to rCor a 1.04, 34% to rCor a 2, 10% to rCor a 8, and 6% to rCor a 11. CONCLUSION Component-resolved in vitro analyses revealed substantial differences in IgE profiles of hazelnut allergic and hazelnut tolerant patients across Europe.

Seasonal variation in food allergy to apple

The aim of the study was to investigate the possibility of a seasonal variation in reactivity to apples in 27 birch pollen allergic patients. Before and during the birch pollen season 1998, the patients were subjected to double-blind, placebo-controlled food challenges (DBPCFCs) with grated fresh Golden Delicious apple followed by an open food challenge with whole fresh apple. The clinical reactions elicited during the challenges were evaluated both by the patients and the investigators. Moreover, the skin reactivity and the in vitro reactivity to apple were evaluated by skin prick test (SPT), leukocyte histamine release (HR), measurement of specific IgE, and immunoblotting experiments. The sensitivity of the DBPCFC, when compared with the result of the open challenge, was 0.74 (14/19) before the season and 0.80 (16/20) during the season. None of the patients reacted to the blinded challenge without a subsequent reaction to the open challenge. One placebo reaction was registered both before and in season, but not in the same patient. The patient scores of the first positive challenges, and the maximal scores of each combined blinded and open challenge session, were significantly increased during the pollen season (P<0.05). The scores of the open challenge were significantly higher than the scores of the DBPCFC both before the season and during the in-season challenges (P<0.05). Specific IgE against Golden Delicious increased during season (P<0.05), while neither SPT, HR, nor immunoblotting experiments could confirm an increase in reactivity. In conclusion, the results of the oral challenge tests indicated an increase in clinical reactivity to apples during the birch pollen season in birch pollen allergic individuals.

Component Resolved Testing for Allergic Sensitization

Component resolved diagnostics introduces new possibilities regarding diagnosis of allergic diseases and individualized, allergen-specific treatment. Furthermore, refinement of IgE-based testing may help elucidate the correlation or lack of correlation between allergenic sensitization and allergic disease. Novel tools to predict severe outcomes and to plan for allergen-specific treatment are necessary, and because only a small amount of blood is needed to test for a multitude of allergens and allergenic components, component resolved diagnostics is promising. A drawback is the risk of overdiagnosis and misinterpretation of the complex results of such tests. Also, the practical use and selection of allergenic components need to be evaluated in large studies including well-characterized patients and healthy, sensitized controls and with representation of different geographical regions.

Maternal occupational exposure to asthmogens during pregnancy and risk of asthma in 7-year-old children: a cohort study

Objectives The objective of this study was to examine whether maternal exposure to asthmogens during pregnancy is associated with the development of asthma in 7-year-old Danish children, taking atopic status and sex into consideration. Design The study is a prospective follow-up of a birth cohort. Setting and participants A total of 41 724 women and their children from The Danish National Birth Cohort were categorised according to maternal occupational exposure. Exposure information was obtained by combining job title in pregnancy and 18 months after pregnancy with a commonly used asthma Job Exposure Matrix. Primary and secondary outcome measures Primary outcome was parent-reported asthma among their 7-year-old children in an internet-based questionnaire. Secondary outcome was asthma among the same children with or without atopic dermatitis and among boys and girls, respectively. Results Prenatal exposure to low molecular weight (LMW) agents was borderline associated with asthma in children with OR 1.17 (0.95 to 1.44) for children with atopic dermatitis and 1.10 (0.98 to 1.22) for children without. Maternal postnatal exposure was associated with asthma (OR 1.15 (1.04 to 1.28). After mutual adjustment,postnatal exposure (OR 1.13 (0.99 to 1.29) and the combined effects of prenatal and postnatal exposure (OR 1.34 (1.19 to 1.51)) seem to increase the risk of asthma in children. No significant associations were observed for other prenatal or postnatal exposures. The gender of the child did not modify the aforementioned associations. Conclusions Maternal occupational exposures during pregnancy do not seem to be a substantial risk factor for the development of asthma in 7-year-old children. Maternal prenatal and postnatal exposures to LMW agents may predispose the propensity of the children to develop asthma. Future studies should prioritise the characterisation of the timing of exposure in relation to the birth.

A comparative study on basophil activation test, histamine release assay and passive sensitization histamine release assay in the diagnosis of peanut allergy

Allergy can be diagnosed using basophil tests. Several methods measuring basophil activation are available. This study aimed at comparing basophil activation test (BAT), histamine release assay (HR), and passive sensitization histamine release assay (passive HR) in the diagnosis of peanut allergy.

Intranasal Corticosteroids Compared with Oral Antihistamines in Allergic Rhinitis: A Systematic Review and Meta-Analysis

Background Intranasal corticosteroids (INS) (corticosteroid nasal sprays) and oral antihistamines (OA) are two of the most common treatments for patients with allergic rhinitis (AR). To our knowledge, there are no systematic reviews on this topic including trials published after 2007. Objective To compare INS with nonsedating OAs as treatments for AR. Methods The systematic review and meta-analysis were based on the Grades of Recommendation, Assessment, Development, and Evaluation principles and the Patient, Intervention, Comparison, and Outcome approach. Primary literature was searched up to January 22, 2015. Criteria for eligibility were randomized controlled trials that compared the efficacy and/or adverse effects of INS and OA in patients with AR. Continuous outcome data were analyzed by using standardized mean differences (SMD) for multiple outcome measures, and mean differences in the case of a single study or outcome. Pooled estimates of effects, 95% confidence interval (CI), were calculated by using random-effects models. Results The meta-analysis included five randomized controlled trials with a total of 990 patients. INS were superior to OAs in improving total nasal symptoms score (SMD -0.70 [95% CI, -0.93 to -0.477]) and in relieving the following: nasal obstruction (SMD -0.56 [95% CI, -0.82 to -0.29]), rhinorrhea (SMD -0.47 [95% CI, -1.00 to 0.05]), nasal itching (SMD -0.42 [95% CI, -0.65 to -0.18]), sneezing (SMD -0.52 [95% CI, -0.73 to -0.32]), and quality of life mean difference -0.90 [95% CI, -1.18 to -0.62]). There was no difference in relief of ocular symptoms (SMD -0.08 [95% CI, -0.23 to 0.08]). In addition, four randomized controlled trials were included in a narrative analysis. The results in the narrative analysis were comparable with those found in the meta-analysis. Conclusion INS were superior to OAs in improving nasal symptoms and quality of life in patients with AR.

Occupational exposure during pregnancy and the risk of hay fever in 7-year-old children

The prevalence of allergic diseases including hay fever has increased in the last decades, especially in Westernised countries. The aim of this study was to analyse whether occupational exposure during pregnancy is associated with development of hay fever in 7‐year‐old Danish children.

Circulating allergen-specific TH2 lymphocytes: CCR4+ rather than CLA+ is the predominant phenotype in peanut-allergic subjects

To the Editor: Early exposure to peanut through a dysfunctional skin barrier may result in sensitization to peanut while oral exposure is suggested to promote tolerance induction. A study on circulating peanut-specific Th cells from peanut-allergic (PA) subjects has supported this hypothesis by demonstrating stronger proliferation of skin-homing cutaneous lymphocyte-associated antigen (CLA) expression compared with gut-homing (a4b7) Th cells. Moreover, high levels of the TH2 subtype-associated skinand lunghoming C-C motif chemokine receptor 4 (CCR4) have been described on Ara h 1–specific Th cells of subjects with PA. It is well recognized that TH2 cells dominate peanut-responsive Th cells in patients with PA. To better understand the mechanism of food allergen sensitization and the importance of exposure route, we aimed to investigate the gutand skin-homing phenotype of circulating human peanut-specific Th cells of PA and nonallergic (NA) subjects. PA subjects all had IgE to Ara h 2 and the median year of latest allergic episode to peanuts was 3 (1-5 years). All PA subjects had concomitant atopic dermatitis (AD) and allergic rhinoconjunctivitis. Moreover, 8 of the 9 subjects with PAwere diagnosed with asthma (see Table E1 in this article’s Online Repository at www. jacionline.org). Circulating Th cells of PA and NA subjects showed similar expression of the investigated skin markers CLA, CCR4, and CCR10 as well as the gut-homing antigen integrin a4b7 (b7) (see Fig E1, A and C, and this article’s Methods section in the Online Repository at www.jacionline.org). Moreover, no differences were found in the frequency of circulating memory (CD161) Th cells and conventional (CRTH2CD161) or pathogenic (CRTH2CD161) TH2-cell subpopulations in PA and NA subjects (Fig E1, D and E). Peanut-responsive Th cells were identified by increased CD154 expression after short-term ex vivo stimulation with whole peanut extract of PBMCs from PA and NA subjects. PA subjects showed stronger peanut-specific CD154Th-cell responses than NA subjects (P 5 .0252, mean frequencies of 113 vs 35 per million Th cells and ratios compared with the unstimulated control of 15 vs 8, Fig 1, A and B). In line with our findings, one study reported comparable frequency of peanut-specific Th cells (100-200 per million Th cells) in PA subjects. Peanut-responsive Th cells of PA subjects had increased expression of the TH2 cell type–associated skinand airwayhoming chemokine receptor CCR4 compared with NA subjects (P 5 .0042, 24% vs 8%), but neither the signature skin-homing antigen CLA (16% vs 14%) nor the other skin-homing chemokine receptor CCR10 (13% vs 7%, Fig 1, D and E). In agreement with our data, another study characterizing Ara h 1–specific Th cells of PA subjects reported expression of CLA in approximately 10% of the cells. Furthermore, no difference in expression of b7 was found in the peanut-responsive Th cells of PA and NA subjects (2.5% vs 3.1%, Fig 1, D and E), an indication of nongut priming. As expected, the largest subpopulation of the peanut-responsive Th cells of PA but not NA subjects was TH2 cells (CRTh2 ) (44% vs 9%, Fig 1, E). Also, most CRTH2-positive peanutspecific Th cells of PA subjects coexpressed CD161, indicative of a pathogenic TH2 cell profile with production of IL-5 (Fig 1, F and G). Finally, peanut-responsive Th cells of PA but not of NA subjects were characterized by high expression of the newly described type 2 immune response–associated receptor CD200R (median fluorescence intensity, 1602 vs 633, Fig 1, H and I). We next characterized the cytokine profile of the peanut-responsive Th cells (see Fig E2, A, in this article’s Online Repository at www.jacionline.org). The peanut-specific Th cells of PA subjects had a larger fraction of conventional (IL-4IL-5, P 5 .0002, 20% vs 1.6%) and pathogenic (IL-4IL-5, P 5 .0002, 29% vs 1.5%) TH2 cells compared with the NA subjects (Fig E2, B and C). This is in agreement with a previous publication, reporting the 2 largest subpopulations of peanut-responsive TH2 cells as IL-5 TH2 (IL-4IL-5) and IL-5TH2 (IL-4 IL-5) cells in PA subjects. Furthermore, the peanut-specific Th cells of PA subjects had a greater percentage of single-positive IL-5IL-4 cells (9.6% vs 1.4%) as well as IL-31, another TH2 subtype-associated cytokine (2% vs 0.6%) than NA subjects (Fig E2, B and C). In contrast, compared with the PA subjects, most peanut-reactive Th cells of NA subjects showed a TH1 profile with more IFN-g– positive cells (10% vs 45%, Fig E2, B and C). Having established that most peanut-responsive Th cells of PA subjects were of a TH2 profile, we failed to find different expression of the canonical skin-homing marker CLA in the PA compared with the NA subjects. Chan et al showed that the isolated CLATh cell fraction of PA subjects primarily produced TH2 cytokines while a TH1 profile was the main population observed of isolated b7 cells in peanut-tolerant subjects. However, the same authors later reported in an elegant transcriptomic study, of sorted CD69 peanut-specific CLA and b7 Th cells, that TH2and TH9-associated cytokines were equally expressed in the CLAand b7-homing Th cells. By analyzing the skinand gut-homing potential of the largest cytokine cell populations of IL-4IL-5, IL-4IL-5, and IFN-g peanut-specific Th cells of PA subjects, unbiased grouping analysis using t-SNE (t-distributed stochastic neighbor embedding) revealed an association of CCR4 but not of CLA to peanut-specific TH2 cells in the PA subjects (Fig 2, A). Interestingly, even though all PA subjects had AD, the main subpopulation of peanut-specific pathogenic (IL-4IL-5) TH2 cells lacked CLA (<1%) and weakly (11%) coexpressed CCR4 (Fig 2, B-D). These findings were unexpected, because the main (>90%) skin-homing T-cell population in subjects with AD is characterized by CLA expression, a surrogate marker for cutaneous T cells. More studies are needed to verify whether the phenotype of circulating peanut-specific Th cells mirrors peanut-specific Th cells located in the airway and skin. Furthermore, CCR4 but not CLAwas in particular expressed by the conventional IL-4IL-5 TH2 cells, with 21% expressing CCR4 (CCR4CLA) in the PA subjects (Fig 2, B-D). However, it would be interesting to study PA subjects without asthma to elucidate whether the CCR4 expression by the conventional TH2 cells is asthma related. On an allergen-specific level, we confirm the link between CCR4 expression of IL-4IL-5 Th

No difference in human mast cells derived from peanut allergic versus non-allergic subjects: Mast cells from allergic and healthy subjects

Mast cells are the primary effector cells of allergy. This study aimed at characterizing human peripheral blood‐derived mast cells (PBdMC) from peanut allergic and non‐allergic subjects by investigating whether the molecular and stimulus‐response profile of PBdMC discriminate between peanut allergic and healthy individuals.

P91 - Pilot study on sensitisation profiles of children with a primary tree nut allergy

Background Plant food allergy is a relatively frequent medical problem in childhood. Peanut and tree nuts are the most common causes. Some are allergic to tree nuts due to pollen cross reactivity whereas others have a primary tree nut allergy. Cross sensitivity is also seen between tree nuts and is serologically well described. But the clinical picture of cross sensitivity amongst tree nut allergic children is less investigated.