A genetic finding by researchers at the National Institutes of Health provides new insight into the cause of a series of related, common and complex illnesses – including hay fever and asthma as well as the skin disorders eczema and psoriasis – and suggests a novel therapeutic approach. These illnesses are essentially inflammatory disorders of the tissues that separate the inside of the body from the outside world, such as the skin and the linings of the throat and lungs.
In the May issue of The Journal of Clinical Investigation , researchers from the National Human Genome Research Institute, the National Eye Institute, and the National Institute of Child Health and Human Development, all part of the National Institutes of Health, report that excessive production of a specific protein disrupts the protective properties of the skin barrier. Once the skin barrier is compromised, allergens can enter the body causing an inflammatory reaction that, in turn, stimulate skin cells to grow rapidly. Rapid skin growth further diminishes the protective function of the skin. The cycle of barrier breakdown, attempted repair, and further barrier breakdown causes the skin to become more porous to allergens that produces common conditions such as psoriasis and eczema.
It may, however, be possible to break the cycle by creating a temporary, artificial barrier on the skin that blocks incoming allergens. The solution could be as simple as developing a lotion that effectively blocks allergens from getting through damaged skin. Keeping allergens out of the skin would keep the immune system from over-stimulating cell growth, giving the skin time to re-create a normal barrier. Current therapies for these skin conditions principally focus on suppressing the immune system, but the medicines used can produce undesired side-effects.
Several recent studies have suggested that defects in the skin barrier may be as important to eczema and psoriasis as the hyperactive response of the immune system. In addition, doctors have observed that individuals with eczema are also likely to develop hay fever and asthma, suggesting a common mechanism for both disorders. The other risk factor for these conditions is having a relative with the disorder, suggesting a genetic connection.
To test whether a defective skin barrier can actually produce these diseases, a team of NIH researchers focused on a specific gene called connexin 26, which makes a protein that forms connections between skin cells that create the normal barrier. When the skin is intact, the production of connexin 26 is turned off once there is enough to hook all the skin cells together. When skin is damaged by a cut or a scrape, connexin 26 is produced while new skin cells reproduce and heal the wound. Researchers have shown that connexin 26 production is turned on in the sore skin of people with psoriasis, but it wasn’t clear what role connexin 26 played in the disorder.
To determine connexin 26’s role in psoriasis, NIH researchers created a line of transgenic mice that over-produce connexin 26. The resulting mice develop psoriatic-type skin sores, just like humans with psoriasis.
The discovery broadens the basic understanding of the causes of skin disorders such as psoriasis and eczema, and may well contribute to the basic understanding of asthma and hay fever, conditions that arise when allergens penetrate the tissue barrier in the lungs and nose, respectively.
Understanding the genetics of skin disorders may well have important implications for more serious illnesses, such as asthma. It is not uncommon for a family doctor to face the dilemma of a child who has eczema and then having to decide how aggressively to treat the disease. Eczema is not particularly dangerous, but children presenting with eczema commonly go on to develop asthma, which severely compromises quality of life and in rare cases can be lethal. Treating eczema with immune-suppressing drugs, which may also prevent asthma from developing, may cause undesirable side effects.
The genetic studies suggest that researchers now need to focus on both turning down the immune response, as well as restoring a normal skin barrier to keep the outside world out of the body.
Message posted by: Rashmi Nemade
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