Waltraud Eder

Association between exposure to farming, allergies and genetic variation in CARD4/NOD1

Background:  Caspase recruitment domain protein (CARD) 4 has been recently identified as an intracellular pattern recognition receptor that interacts with muropeptides found in common Gram‐negative bacteria. We therefore aimed to explore whether the previously observed inverse association between exposure to microbial products and asthma and allergies in childhood is modified by genetic variation in CARD4.

Hygiene hypothesis and endotoxin: what is the evidence?

Purpose of reviewThe hygiene hypothesis has gained strong support over the past few years. Exposure to microbial products in early life could be an underlying factor in this hypothesis, but the mechanisms that lead from a less clean and more crowded environment to a lower prevalence of asthma and allergies are not known. Among the variety of potential microbial molecules that may confer protection against the development of asthma and allergies, endotoxin, a component of Gram-negative bacteria, has incited lively as well as controversial discussions. This review focuses on recent studies on endotoxin and its role in the context of the hygiene hypothesis. Recent findingsResults from cross-sectional surveys, prospective cohorts, and experimental studies in vitro and in rodents suggest that exposure to house dust endotoxin in early life protects from atopic sensitization and IgE-mediated diseases, but is a risk factor for wheezing in infancy. SummaryNumerous studies have supported the hygiene hypothesis, but whether endotoxin by itself confers the protection or whether it acts as a marker for another environmental exposure is still unclear. The challenge for the future will be to identify those factors that confer the protection proposed by the hygiene hypothesis, and to find strategies to modify the environment without causing harm to susceptible individuals.

The protective effect of farm animal exposure on childhood allergy is modified by NPSR1 polymorphisms

Background: Little is known about the asthma candidate gene neuropeptide S receptor 1 (NPSR1) in relation to environmental exposures, but recent evidences suggest its role as an effect modifier. Objectives: To explore the interaction between NPSR1 polymorphisms and environmental exposures related to farming lifestyle and to study the in vitro effects of lipopolysaccharide (LPS) stimulation on NPSR1 expression levels. Methods: We studied 3113 children from PARSIFAL, a European cross-sectional study on environmental/lifestyle factors and childhood allergy, partly focused on children brought up on a farm. Information on exposures and outcomes was primarily obtained from parental questionnaires. Seven tagging polymorphisms were analysed in a conserved haplotype block of NPSR1. Multivariate logistic regression was used to evaluate a multiplicative model of interaction. NPSR1 protein and messenger RNA (mRNA) levels in monocytes were measured after LPS stimulation by fluorescence activated cell sorting (FACS) and quantitative real-time polymerase chain reaction (PCR). Results: A strong interaction was seen between current regular contact to farm animals and several NPSR1 polymorphisms, particularly rs323922 and rs324377 (p<0.005), with respect to allergic symptoms. Considering the timing of initiation of such current regular farm animal contact, significant interactions with these and two additional polymorphisms (SNP546333, rs740347) were revealed. In response to LPS, NPSR1-A protein levels in monocytes were upregulated (p = 0.002), as were NPSR1-A mRNA levels (p = 0.02). Conclusions: The effect of farm animal contact on the development of allergic symptoms in children is modified by NPSR1 genetic background.