AETIOLOGY and SUSCEPTIBILITY
The main objective of Working Group 1 is to initiate and coordinate the activities to identify intrinsic and environmental factors involved in the aetiology and susceptibility to OSD. While some genetic and environmental causative exposures have already been identified from previous studies, this project offers the opportunity to identify a wide array of novel risk factors, especially genetic ones, in multiple populations. These include mutations in genes encoding for barrier related proteins such as filaggrin, skin lipids, tight junctions and skin proteases but also mutations in genes coding for factors that could be associated with increased immune reactivity. DNA will be collected from patients (and controls when appropriate) either from blood samples or buccal swabs. DNA collection and storage and genotyping will be coordinated by the Action members with the expertise in DNA banking and genetic analysis. Information about environmental risk factors including occupational and domestic skin exposures to irritants and allergens as well as lifestyle factors such as smoking, and alcohol intake will be obtained using a standard (validated) questionnaire. Quantitative information about allergens deposited onto the skin will be obtained by skin exposure assessments. WG1 will not only provide more insight in the mechanisms underlying development of OSD but also facilitate identification of phenotypic biomarkers that may allow identifying individuals at risk and detect skin barrier impairment before clinical signs occur.
The main approaches will be:
- Epidemiological studies (e.g. case-control and prospective cohort studies) on intrinsic and environmental risk factors in OSD. Cooperation between different institutions will facilitate harmonization and standardization of diagnostics, exposure assessment, and choice of the control group and investigated risk factors.
- Experimental studies in human volunteers on genotype-phenotype relation aiming at identifying of phenotypic biomarkers (e.g. profiles of skin lipids/proteins/skin irritability and atopy) as predictive tools in individuals at risk for OSD and (early) diagnostics.
The expected outcomes are:
- Establishment of large and well defined disease cohorts with documented information on environmental exposure and clinical features across COST countries
- Identification of genetic alterations conferring an increased risk for OSD
- Identification of phenotypic biomarkers as predictive tools for individuals at risk for OSD suitable for pre-employment/on-the-job counselling
- Identification of new potential diagnostic and therapeutic targets
- Identification of vulnerable groups that will benefit from specifically tailored individual prevention strategies for OSD