Nanna Juel-Berg

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.

The immunoglobulin superfamily member CD200R identifies cells involved in type 2 immune responses

The pathology of allergic diseases involves type 2 immune cells, such as Th2, ILC2, and basophils exerting their effect by production of IL‐4, IL‐5, and IL‐13. However, surface receptors that are specifically expressed on type 2 immune cells are less well documented. The aim of this investigation was to identify surface markers associated with type 2 inflammation.

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.

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

Dietary exposure to benzoxazinoids enhances bacteria-induced monokine responses by peripheral blood mononuclear cells

SCOPE To examine potentially immunomodulating effects of dietary benzoxazinoids (BXs), present in cereal grains. METHODS AND RESULTS Nineteen healthy volunteers were randomly distributed into two groups, who received diets with high or low content of BXs for 3 wk. After a weeks wash-out, the groups switched diets. Peripheral blood mononuclear cells (PBMCs) were stimulated with Porphyromonas gingivalis, Escherichia coli lipopolysaccharide (LPS), or tetanus toxoid (TT). PBMCs from a healthy donor received the same stimuli in presence of serum from each participant receiving BXs. The production of monokines, T-cell cytokines and T-helper cell proliferation were assessed. A 3-wk diet with high BX content enhanced IL-1β responses against LPS and P. gingivalis, as well as TNF-α response against P. gingivalis, after 24 h of stimulation. Moreover, IL-6 was found to be increased after 7 days of stimulation with LPS. No effect was observed on T-cell cytokines or proliferation. BX levels in serum after a single meal did not modify cytokine responses. CONCLUSION High dietary intake of BXs enhances bacteria-induced production of pro-inflammatory monokines by PBMCs, but not T-cell responses; presumably due to intrinsic changes within PBMCs, built up over 3 wk of BX-rich diet, rather than to an immediate effects of BXs contained in serum.

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.