Severe eczema - also known as atopic dermatitis - is a chronic inflammatory skin condition that is driven by an allergic reaction. Researchers from SciLifeLab at Uppsala University have found a total of 141 regions or genes in our genetic material that largely explain the genetic risk underlying eczema as well as asthma and hay fever. As many as 41 of the genes identified have not previously been linked to an elevated risk for these diseases.
The risk of developing asthma, hay fever or eczema is affected by genes, environment and lifestyle factors. Many patients diagnosed with one of these diseases also develop the other two at some stage in life. Although previous studies have found many genes that exert an effect on these diseases, research has been unable to explain the whole genetic background to the origin of asthma, hay fever and eczema.
In this study - published in Human Molecular Genetics – researchers analyzed self-reported data from 350,000 participants in Britain's UK Biobank. Millions of gene positions were tested for their effect on people's risk of being diagnosed with eczema, asthma, and hay fever. The 41 new genetic finds were also tested in an independent group of 110,000 clients of the American company 23andMe. This testing verified that most of these new genetic variants have an effect on the individual's risk of developing disease.
The study showed that a large number of the genes identified involve a raised risk for all three diseases and that the elevated risk of suffering from allergy when asthma is diagnosed - or the elevated risk of asthma when allergy is diagnosed - seems to be largely due to genetic factors. The study also identified several genes that boost the risk of one of these diseases in relation to the others, which demonstrates that a number of more disease-specific effects also exist.
All three diseases arise through a complex association among several genes and also with environmental and lifestyle factors. To improve the patients' everyday lives, it is important to develop drugs that are adapted to individual patients' genetic risks, and also to understand how our environment and lifestyle can prevent disease and improve symptoms of disease. “External factors also affect our risk for these complex traits, and an elevated risk doesn't mean we're going to develop the disease," says Weronica Ek, researcher at the Department of Immunology, Genetics and Pathology at Uppsala University. "The results from this study are helping us to reach a greater understanding of why certain individuals are at higher risk of developing asthma and allergies, and we hope the results will be put to use both in clinical diagnostics and in drug development," Ek added.
Severe Eczema Key Driver Discovered
Researchers at La Jolla Institute revealed an important player that promotes skin inflammation in atopic dermatitis and the characteristic thickening of the skin. The findings – in the Journal of Experimental Medicine - demonstrate that LIGHT, a member of the tumor necrosis factor (TNF) super family, directly controls the hyperproliferation of keratinocytes as well as the expression of periostin, a protein that contributes to the clinical features of atopic dermatitis as well as other inflammatory skin diseases such as scleroderma.
A therapeutic antibody that neutralizes the activity of LIGHT successfully suppressed disease symptoms after they first appeared, suggesting that therapies based on blocking LIGHT may add a valuable treatment option for patients suffering from severe eczema. LIGHT is a cytokine primarily produced by T cells and exerts its function through two receptors, HVEM and LT?R. "Periostin is being used in the clinic as a marker for allergic diseases such as asthma as well as atopic dermatitis," says senior author Michael Croft, Ph.D., professor and head in the Division of Immune Regulation. "The fact that LIGHT acts upstream of periostin and is controlling its production really reinforces the idea that this is potentially a very good clinical target for treatment of atopic dermatitis and other inflammatory skin diseases."
To find out whether LIGHT contributes to skin inflammation in atopic dermatitis, Rana Herro, Ph.D., an instructor in the Croft lab, used an experimental model for atopic dermatitis that replicates the human disease. Her experiments revealed that LIGHT-deficient mice only displayed minimal clinical symptoms compared to normal control mice. The same was true for animals that only lacked the LIGHT-receptor HVEM in keratinocytes, the predominant cell type in the outermost layer of the skin.
LIGHT also induces the expression of periostin – a protein highly expressed in the skin of patients with atopic dermatitis and scleroderma. Animal studies have found it is essential for skin inflammation although exactly how it functions is still being debated. The researchers used an existing therapeutic antibody to block the interaction of LIGHT with its receptor, HVEM, after disease had already manifested. The antibody treatment suppressed inflammation and strongly reduced epidermal thickening. "We knew that LIGHT acts as a pro-inflammatory molecule on immune cells but we were able to implicate, for the first time in a disease setting, that this molecule acts on non-immune cells like the structural cells of the skin," Herro said. "LIGHT directly drives fibrosis, a structural remodeling process that leads to the thickening and hardening of the skin. That's great news for patients suffering from eczema. Our findings suggest that therapies that block LIGHT signaling might halt atopic dermatitis in humans and maybe even reverse disease symptoms."
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With over 30 years of writing and editing experience for newspapers, magazines and corporate communications, Kevin Kerfoot writes about natural health, nutrition, skincare and oral hygiene for Trusted Health Products’ natural health blog and newsletters.
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