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Scratching Below the Surface - Filaggrin mutations, atopic eczema, hay fever and asthma in childrenStephan Weidinger, MD, Maureen O’Sullican, MD, Thomas Illig, PhD, Hansjörg Baurecht, MSc, Martin Depner, MSc, Elke Rodriguez, MSc, Andreas Ruether, PhD, Norman Klopp, PhD, Christian Vogelberg, MD, Stephan K Weiland, MD, WH Irwin McLean, PhD, DSc, FRSE, Erika von Mutius, MD, Alan D Irvine, MD, Michael Kabesch, MD A child with atopy makes allergic antibodies (IgE) after exposure to allergens like trees, grasses, weeds, molds, pets, and foods. Common manifestations of atopic disease are eczema, allergic rhinitis and asthma, but a common linkage between these diseases has not been demonstrated. Some atopic children have all three diseases; some have one, but not the others. Two years ago, discovery of the association between a mutation of the filaggrin gene (FLG) and eczema was a breakthrough. This gene makes a protein called filaggrin which is found in the outermost layers of normal skin. The protein is vital in the skin’s function as a barrier, helping to form a protective layer at the surface of the skin that keeps water in and foreign organisms out. When the body can’t make this protein correctly, the skin dries out too easily and constantly flakes off. In addition to keeping water in, the skin barrier keeps stuff from penetrating the skin’s surface. In people with filaggrin mutations foreign substances can easily pass through the skin and are identified by the immune system as external threats to be attacked. A child with atopy’s immune system then makes antibodies to these foreign invaders to fight them off. Although the invaders are generally harmless pollens and danders, the flawed skin is the battlefield and gets further damaged in its mistaken defense. Understanding this mechanism has been an important step forward. The question now has become, “Is there also a relationship between this same genetic flaw and allergic rhinitis or asthma?” in an effort to better understand the genetic cause of these complex atopic diseases and their interrelationships, a study by Weidinger et al looked at the FLG mutation and its links to rhinitis and asthma. The authors found that this gene defect in white children was also associated with a significant risk for hay fever, independent of eczema. The risk for asthma, however, was only found in cases where the child had both asthma and eczema. Based on these results, the authors consider filaggrin to be a major gene in the development of eczema, atopic sensitization and allergic rhinitis, and a major effect in asthma that is limited to children who also have eczema. The nature of the relationship between these atopic diseases and asthma can only be guessed at. It may be that the immune system is primed by pollens and danders passing through the "leaky" skin, leading to asthma when allergens later enter the lungs. Currently, there are no known therapies that can cure allergic inflammation. So far we mostly just treat symptoms. If we can somehow fix the problem caused by the skin’s filaggrin shortage we may be able to create new strategies in prevention and treatment of these common diseases. |
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