Carla A.F.M. Bruijnzeel-Koomen

A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force.

This report has been prepared by an EAACI task force representing the five EAACI Sections and the EAACI Executive Committee composed of specialists that reflect the broad opinion on allergy expressed by various clinical and basic specialties dealing with allergy. The aim of this report is to propose a revised nomenclature for allergic and related reactions that can be used independently of target organ or patient age group. The nomenclature is based on the present knowledge of the mechanisms which initiate and mediate allergic reactions. However, the intention has not been to revise the nomenclature of nonallergic hypersensitivity.

A role for Th1 and Th2 cells in the immunopathogenesis of atopic dermatitis.

Abstract Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intensely pruritic subacute and chronic eczematous plaques, the pathogenesis of which appears to involve a complex interplay of genetic, pharmacological, environmental and psychological factors. Here, Markus Grewe and colleagues propose that the development of skin lesions in AD patients results from sequential activation of T helper 2 (Th2)- and Th1-type cells.

Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial TH2 response to a TH1 response in situ: An immunocytochemical study

In the pathogenesis of atopic dermatitis (AD), IgE plays an important role; and TH2 cells, producing IL-4, have been ascribed a key role in allergic diseases such as AD. To investigate the role of TH subpopulations in the onset and continuation of AD, we performed atopy patch tests (APTs) with house dust mite allergen in patients with AD. Punch biopsy specimens were taken from the APT site, and sections were immunocytochemically double-stained for IL-4 and interferon-gamma together with different membrane markers. This provides a unique model for studying the kinetics of the TH0, TH1, and TH2 responses in situ. The results show that in lesional skin interferon-gamma-positive cells predominate over IL-4-positive cells. The interferon-gamma-positive cells are mainly CD3+ and, in particular, CD4+ cells; the remainder are CD8+, RFD-1+, and RFD-7+ cells. The IL-4-positive cells are exclusively CD4+ T cells; no eosinophils or mast cells were found to stain for IL-4. With regard to the TH cell response, a clear dichotomy of the eczematous response to allergen in skin was observed. In the initiation phase IL-4 production by TH2 and TH0 cells is predominant over interferon-gamma production by TH1 and TH0 cells. In the late and chronic phases the situation is reversed and interferon-gamma production by TH1 and TH0 cells predominates over IL-4 production by TH2 and TH0 cells. Understanding the relationship between the observed biphasic response and clinical manifestation of AD is important for the development of therapeutic strategies.

Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis.

Background:  Eosinophils may play an important role in the pathogenesis of atopic dermatitis (AD). Interleukin‐5 is essential for eosinophil growth, differentiation and migration. A monoclonal antibody to human interleukin‐5 (mepolizumab) was developed for atopic diseases. This study was designed to study the effect of mepolizumab in AD.

A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much?

Background While the ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE‐mediated food allergies, little information is known regarding these threshold doses for specific allergenic foods. While low‐dose challenge trials have been conducted on an appreciable number of allergic individuals, a variety of different clinical protocols were used making the estimation of the threshold dose very difficult.

Acute allergic reactions in children with AEDS after prolonged cow's milk elimination diets

Background:  Food allergy is not always correctly diagnosed in children with atopic eczema dermatitis syndrome (AEDS) and treatment with an avoidance diet is not without danger.

Efficacy of birch-pollen immunotherapy on cross-reactive food allergy confirmed by skin tests and double-blind food challenges

Background The effect of birch‐pollen immunotherapy (IT) on cross‐reactive food allergies is controversial.

Peanut epitopes for IgE and IgG4 in peanut-sensitized children in relation to severity of peanut allergy

BACKGROUND Better understanding of the relationship between antibody response to peanut and clinical sensitivity might lead to more accurate prognostication. OBJECTIVE We sought to investigate peanut-specific IgE and IgG4 epitope diversity in relation to challenge-defined clinical sensitivity to peanut in a group of peanut-sensitized children. METHODS Clinical sensitivity was determined by means of double-blind, placebo-controlled peanut challenges in 24 sensitized children. Six atopic control subjects were included. Specific IgE and IgG4 binding to 419 overlapping 15-amino-acid peptides representing the sequence of recombinant Ara h 1, Ara h 2, and Ara h3 was analyzed by means of microarray immunoassay. RESULTS Peanut-sensitized patient sera bound significantly more IgE and IgG4 epitopes than control sera. This patient group reacted to the same Ara h 1, Ara h 2, and Ara h 3 epitopes as reported previously. There was a positive correlation between IgE epitope diversity (ie, number of epitopes recognized) and clinical sensitivity (r = 0.6), such that patients with the greatest epitope diversity were significantly more sensitive than those with the lowest diversity (P = .021). No specific epitopes were associated with severe reactions to peanut. IgG4 binding was observed to largely similar epitopes but was less pronounced than IgE binding and did not relate to the clinical sensitivity to peanut. IgE and IgG4 epitope-recognition patterns were largely stable over a 20-month period. CONCLUSION Clinical sensitivity, as determined by means of double-blind, placebo-controlled peanut challenge, is positively related to a more polyclonal IgE response, which remains stable over time.

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

BACKGROUND Component-resolved diagnosis has been shown to improve the diagnosis of food allergy. OBJECTIVE We sought to evaluate whether component-resolved diagnosis might help to identify patients at risk of objective allergic reactions to hazelnut. METHOD A total of 161 hazelnut-sensitized patients were included: 40 children and 15 adults with objective symptoms on double-blind, placebo-controlled food challenges (DBPCFCs) and 24 adults with a convincing objective history were compared with 41 children and 41 adults with no or subjective symptoms on DBPCFCs (grouped together). IgE levels to hazelnut extract and single components were analyzed with ImmunoCAP. RESULTS IgE levels to hazelnut extract were significantly higher in children with objective than with no or subjective symptoms. In 13% of children and 49% of adults with hazelnut allergy with objective symptoms, only sensitization to rCor a 1.04 was observed and not to other water-soluble allergens. Sensitization to rCor a 8 was rare, which is in contrast to rCor a 1. Sensitization to nCor a 9, rCor a 14, or both was strongly associated with hazelnut allergy with objective symptoms. By using adapted cutoff levels, a diagnostic discrimination between severity groups was obtained. IgE levels to either nCor a 9 of 1 kUA/L or greater or rCor a 14 of 5 kUA/L or greater (children) and IgE levels to either nCor a 9 of 1 kUA/L or greater or rCor a 14 of 1 kUA/L or greater (adults) had a specificity of greater than 90% and accounted for 83% of children and 44% of adults with hazelnut allergy with objective symptoms. CONCLUSION Sensitization to Cor a 9 and Cor a 14 is highly specific for patients with objective symptoms in DBPCFCs as a marker for a more severe hazelnut allergic phenotype.

CD8(+) T cells in the lesional skin of atopic dermatitis and psoriasis patients are an important source of IFN-γ, IL-13, IL-17, and IL-22.

Although CD4(+) T cells are known to contribute to the pathology of atopic dermatitis (AD) and psoriasis, the role of CD8(+) T cells in these diseases remains poorly characterized. The aim of this study was to characterize the cytokine production of T cells from AD and psoriasis skin. We found that CD4(+) T cells isolated from AD skin were largely Th2 (T helper type 2) biased, in agreement with prior reports. However, we also observed large numbers of CD8(+) T cells producing IL-13, IFN-γ, and IL-22. We observed increased numbers of CD8(+) T cells isolated from AD skin, and immunohistochemistry studies confirmed the presence of CD8(+) T cells in the dermis and epidermis of AD skin lesions. Surprisingly, T-cell cytokine production was similar in the lesional and nonlesional skin of patients with AD. T cells from psoriatic lesional skin predominantly produced IFN-γ, IL-17, and IL-22, in agreement with prior studies. However, in addition to Th17 cells, we observed high percentages of CD8(+) T cells that produced both IL-22 and IL-17 in psoriatic skin lesions. Our findings demonstrate that CD8(+) T cells are a significant and previously unappreciated source of inflammatory cytokine production in both AD and psoriasis.