Stealing a march on allergy
According to ground-breaking research supported by the NCRC, the primary suspect for causing eczema in children – a long-term, debilitating condition affecting the skin – is a defective gene rather than a misfiring immune system as had been believed by the medical community.
Until recently, it was believed that eczema in children arose because of a fault in the immune system, the body's defensive system that fights infection and disease. Work by an NCRC research group has challenged this.
In 2006, Professor Alan Irvine, a Consultant Dermatologist at Our Lady's Children's Hospital, Crumlin (OLCHC), began to build a large-scale, multi-site study of eczema in children, aimed at finding out how the condition arose, how it developed, and how it was linked to the later development of allergy and asthma. At end of 2015 there were 4,300 children recruited to the study across 30 sites in Ireland, Northern Ireland, Scotland and England. This is the largest study of moderate-to-severe cases of eczema in the world.
The ground-breaking finding by Professor Irvine, and collaborators, was that errors in a gene called Filaggrin – FLG for short – were linked to eczema. The FLG gene is important because, when functioning properly, it 'tells' the skin cell to produce Filaggrin, a protein needed to hold the skin together. If the gene is not functioning properly however, a faulty protein is produced, resulting in a defective protective barrier. The skin is then more porous, allowing tiny particles from the environment to trigger an immune response in the skin, resulting in eczema.
This work was reported in the world's leading scientific journals, including five papers in Nature Genetics, and major media outlets, including The New York Times, and changed the way scientists and clinicians now view eczema's roots
Teasing out the steps from faulty gene to the skin condition was speeded up by a long-standing collaboration with Professor Padraic Fallon, Stokes Professor of Immunology in TCD. He models human immune diseases in mice allowing the role of genes and environment in disease to be examined in a way not possible in humans. The discoveries made in the lab are then translated back to the clinic.
They have gone on to show that the errors in the FLG gene are not only a significant risk factor for eczema, but are also linked with other allergies.
Eczema is often, sadly, just the first step in an 'allergic march' where young children with eczema go on to develop allergic conditions as they age. About half of all children with eczema will develop asthma, and an even higher number, about 70%, will go on to develop hay fever.
The identification of a defective FLG gene at the root of eczema is crucial to stopping the allergic march, as eczema is often the first step in that march.
The overall aim of this work is to harness this knowledge to help develop better treatments; knowing the defect in the skin barrier is a major step in this direction.
How this research helped
It provides a major step forward in understanding the key fault in the skin of children with eczema