Scientists identify a protein that switches on allergic itching

Incessant itching is a harsh and problematic reality for eczema sufferers, causing all sorts of problems that can range from skin infections to trouble sleeping. Scientists investigating the biological processes behind the condition have uncovered a protein in the skin they say acts as a switch for itch-related neurons, offering a potential new target in the ongoing search for more effective treatments.

A number of factors can cause outbreaks for eczema sufferers, including irritants, reactions to certain foods, and allergies. The itching sensation, which often goes with other symptoms such as dryness and redness, is driven by neurons in the skin, which take their cues from sensory cells based at the root of the spinal nerves.

Researchers at North Carolina State University have been examining this pathway through experiments on mice, in which they chemically induced cases of eczema. When exposing the animals to common allergens such as dust mites, the scientists observed an increase in a skin protein called periostin, which served to greatly exacerbate the itch response.

“We have found that periostin, a protein that is produced abundantly in skin as part of an allergic response, can interact directly with sensory neurons in the skin, effectively turning on the itch response,” says Santosh Mishra, lead author of a paper. “Additionally, we identified the neuronal receptor that is the initial connection between periostin and itch response.”

The receptor protein, called αvβ3, is expressed in the skin’s sensory neurons and acts as the connector for periostin in driving the increased itch response. The team found that by switching off the receptor, they could break this important chain and “significantly” reduce the severity of the itching.

“Periostin and its receptor connect the skin directly to the central nervous system,” Mishra says. “We have identified the first junction in the itch pathway associated with eczema. If we can break that connection, we can relieve the itch.”

The research was published in the journal Cell Reports

https://newatlas.com/medical/protein-switch-allergic-itching-eczema/

Gene defects linked to eczema

wheeze and nasal disease among babies

Research shows ‘personalised’ medicine approach could dramatically improve patients’ lives

A link has been discovered between a common gene defect and eczema, nasal blockage and wheeze among babies as young as six months, according to a new study at Brighton and Sussex Medical School (BSMS). The research raises new questions about how soon in life these defects could start affecting babies, resulting in serious health problems, and suggests treatment targeted towards children carrying these genetic defects started soon after birth could improve their lives.

The protein filaggrin is present in the skin and nasal cavity, helping to maintain the skin barrier, and previous studies have shown defects in the gene synthesising filaggrin are strongly linked to the risk of developing eczema and how serious the eczema and asthma turned out to be over childhood.

Professor Somnath Mukhopadhyay, Chair in Paediatrics at BSMS, said: “In the first study of this kind, we recruited mothers in the antenatal clinic and followed up the babies through infancy, in order to define the link between these gene defects, the resultant skin problem, and eczema, wheeze and nasal blockage, in early infancy. Our striking finding establishing this link could mean that some babies with these gene defects could be getting primed from birth or soon after, for a life of suffering from allergy-related disease.”

The GO-CHILD study recruited 2,312 pregnant women in England and Scotland, who gave a cord blood sample at birth or saliva in infancy for genotyping of the babies. Babies were followed up for symptoms related to allergic diseases such as dry skin, eczema, wheeze and nasal blockage, at the ages of 6, 12 and 24 months by postal questionnaires sent to the carers.

The gene defects made eczema, wheeze and nasal blockage worse at six months. While the defects were affecting eczema at one year, they were no longer worsening wheeze and nasal blockage at this age. At two years, they were principally worsening eczema and nasal blockage, but not affecting wheeze. “The problems affecting the child change over time, filaggrin gene variation representing one major ensemble within the grand orchestra of allergic disease,” said Professor Mukhopadhyay.

He added: “The use of simple emollients from birth targeted towards those who have these gene defects may help correct this problem, thus alleviating suffering in infancy and also through life. This new approach for targeting treatment according to genetic information is known as precision or personalised medicine and a future trial could represent the first application of this exciting and novel approach in little babies otherwise primed to develop chronic disease from an early age.

“This skin barrier defect leads to selective entry of allergens to increase the burden of disease. Whether such barrier defects could make us more vulnerable to agents causing infection, such as viruses, has not yet been addressed. We are in the midst of a pandemic where some people are affected but many are not. Could a defective outer barrier in skin and mouth be making some of us more vulnerable? If so, would identifying patients carrying these defects help us better protect those that are more vulnerable?”

The study was funded by Sparks Children’s Medical Research Charity and the Rockinghorse Children’s Charity. It was published in the Journal of Allergy and Clinical Immunology, the world’s top allergy journal, and can be accessed at: https://www.jacionline.org/article/S0091-6749(20)30348-1/abstract