Microarray Technology May Reveal the Contribution of Allergen Exposure and Rhinovirus Infections as Possible Triggers for Acute Wheezing Attacks in Preschool Children

Allergen exposure and rhinovirus (RV) infections are common triggers of acute wheezing exacerbations in early childhood. The identification of such trigger factors is difficult but may have therapeutic implications. Increases of IgE and IgG in sera, were shown against allergens and the N-terminal portion of the VP1 proteins of RV species, respectively, several weeks after allergen exposure or RV infection. Hence, increases in VP1-specific IgG and in allergen-specific IgE may serve as biomarkers for RV infections or allergen exposure. The MeDALL-allergen chip containing comprehensive panels of allergens and the PreDicta RV chip equipped with VP1-derived peptides, representative of three genetic RV species, were used to measure allergen-specific IgE levels and RV-species-specific IgG levels in sera obtained from 120 preschool children at the time of an acute wheezing attack and convalescence. Nearly 20% of the children (22/120) showed specific IgE sensitizations to at least one of the allergen molecules on the MeDALL chip. For 87% of the children, increases in RV-specific IgG could be detected in the follow-up sera. This percentage of RV-specific IgG increases was equal in IgE-positive and -negative children. In 10% of the children, increases or de novo appearances of IgE sensitizations indicative of allergen exposure could be detected. Our results suggest that, in the majority of preschool children, RV infections trigger wheezing attacks, but, in addition, allergen exposure seems to play a role as a trigger factor. RV-induced wheezing attacks occur in IgE-sensitized and non-IgE-sensitized children, indicating that allergic sensitization is not a prerequisite for RV-induced wheeze.     

The neural correlates of worry in association with individual differences in neuroticism

The tendency to worry is a facet of neuroticism that has been shown to mediate the relationship between neuroticism and symptoms of depression and anxiety. The aim of the current study was to investigate the neural correlates of state worry in association with neuroticism. One‐hundred twenty participants were selected from an initially recruited sample of 240 women based on their neuroticism score. First, participants completed a questionnaire to assess the excessiveness and uncontrollability of pathological worry. Second, we measured brain activation with functional magnetic resonance imaging (fMRI) while participants were randomly presented with 12 worry‐inducing sentences and 12 neutral sentences in a mood induction paradigm. Individuals scoring higher on neuroticism reported to worry more in daily life and to have generated more worry‐related thoughts after the presentation of a worry‐inducing sentence. Furthermore, imaging results showed the involvement of default mode and emotional brain areas during worry, previously associated with self‐related processing and emotion regulation. Specifically, cortical midline structures and the anterior insula showed more activation during worry, when individuals indicated to have generated more worry‐related thoughts. Activation in the retrosplenial and visual cortex was decreased in individuals scoring higher on neuroticism during worry, possibly suggesting reduced autobiographical specificity and visual mental imagery. In the literature, both these processes have been related to the cognitive avoidance of emotional distress. Excessive worry features in a number of emotional disorders and results from studies that elucidate its neural basis may help explain how and why neuroticism contributes to vulnerability for psychopathology. Hum Brain Mapp 35:4303–4315, 2014. © 2014 Wiley Periodicals, Inc .     

Proteolytic,lipidergic and polysaccharide molecular recognition shape innate responses to house dust mite allergens

House dust mites (HDMs) are sources of an extensive repertoire of allergens responsible for a range of allergic conditions. Technological advances have accelerated the identification of these allergens and characterized their putative roles within HDMs. Understanding their functional bioactivities is illuminating how they interact with the immune system to cause disease and how interrelations between them are essential to maximize allergic responses. Two types of allergen bioactivity, namely proteolysis and peptidolipid/lipid binding, elicit IgE and stimulate bystander responses to unrelated allergens. Much of this influence arises from Toll-like receptor (TLR) 4 or TLR2 signalling and, in the case of protease allergens, the activation of additional pleiotropic effectors with strong disease linkage. Of related interest is the interaction of HDM allergens with common components of the house dust matrix, through either their binding to allergens or their autonomous modulation of immune receptors. Herein, we provide a contemporary view of how proteolysis, lipid-binding activity and interactions with polysaccharides and polysaccharide molecular recognition systems coordinate the principal responses which underlie allergy. The power of the catalytically competent group 1 HDM protease allergen component is demonstrated by a review of disclosures surrounding the efficacy of novel inhibitors produced by structure-based design.