Short summary

We investigate the risk factors and immunologic factors associated with atopic dermatitis and asthma. We recruit from the Odense Child Cohort and investigate filaggrin gene and its protein biomarkers. We aim to identify the different mechanisms that help to regulate atopic dermatitis and asthma as well as causal link between atopic dermatitis and asthma.

Rationale

Atopic dermatitis (AD) has significantly increased since the 1960s and now affects up to 25% of children worldwide. The disease is caused by a complex interplay between gene and environment, skin barrier and immune dysfunction. One important gene is the filaggrin (FLG) gene, which codes for an important skin cell protein that helps to maintain the integrity of the skin barrier and keeps the skin well-hydrated. A mutation in the gene is associated with AD, but this does not explain the majority of patients- less than a third of AD patients bear the gene mutation. However, recent studies have shown that filaggrin protein is significantly decreased in AD patients, in both those who have the mutation and those who do not. Population studies to date have taken into account gene status (whether the patient has the mutation or not), but none have taken into account protein levels. Due to the lack in current knowledge, we propose a case-control children's cohort study to investigate the environmental factors that may cause the increase or decrease in filaggrin protein levels by measuring its breakdown products. We use a new non-invasive technique called tape-stripping to measure these breakdown products and also examine factors in the immune system that may affect protein levels. 

The FLG gene mutation is also associated with an increased risk of developing asthma, in those patients with a history of AD. The driving mechanism from AD to asthma is currently unknown. The trigger may possibly involve signals from the immune system, particularly from T-helper 2 (Th2) cytokines, which are protein messengers strongly associated with allergic disease. We investigate specifically the cytokine CCL18, a chemical messenger that is present in significantly higher levels in both AD and asthmatic patients compared with healthy controls. Our study investigates a possible pathway in which CCL18 triggers naive T cells in the immune system to become memory T cells, then signals the replication of these memory T cells that are later involved with the development of asthma.

The project contributes significantly to the understanding of the different mechanisms that help to regulate AD and asthma. New knowledge on environmental factors and their influence on filaggrin expression is significant in that it can lead to better and more feasible prevention strategies for patients and clinicians and affect disease prevalence. Investigation of CCL18 as a causal link between AD and asthma opens up doors to a novel area of research and possible treatment options with focus on new prevention strategies.

Clinical Relevance

We aim to identify environmental risk factors that affect filaggrin expression, which can lead to better and more feasible treatment and prevention strategies for patients and clinicians. In light of the strong association between atopic dermatitis and asthma, these prevention strategies could affect both disease prevalences. Our investigation of CCL18 as a causal link between atopic dermatitis and asthma can lead to new prevention options. The recent identification of the CCL18 receptor in humans opens the potential for a focus on novel prevention strategies in which receptor antagonism at an early stage could decrease the prevalence of asthma.

Description of the cohort

Our cohort is composed of 7 year old children participating in the Odense Child Cohort with atopic dermatitis, asthma or healthy controls.

Data and biological material

Data is collected from questionnaires, medical journals, blood and skin samples as well as buccal swabs.

Collaborating researchers and departments

HC Andersen Hospital, Odense University Hospital

• Professor Susanne Halken, D.M. Sci.

Allergy Center, Odense University Hospital

• Professor Charlotte Mørtz, PhD

Department of Clinical Immunology, Odense University Hospital

• Professor Torben Barington, D.M. Sci.

Department of Environmental Medicine, Odense University Hospital

• Professor Tina Kold Jensen, PhD