Health Scan: Ungluing the complexity of allergy

Tiny but complex units of protein in the skin – called desmosomes from a combination of Greek words – have been found to play an important role in preventing allergic disorders.

By JUDY SIEGEL-ITZKOVICH
allergies pollen 370 (photo credit: reuters)
allergies pollen 370
(photo credit: reuters)
Tiny but complex units of protein in the skin – called desmosomes from a combination of Greek words – have been found to play an important role in preventing allergic disorders. This discovery was made recently by an international group of researchers, headed by Prof. Eli Sprecher at Tel Aviv Sourasky Medical Center and Prof. Kathleen Green of Northwestern University in Illinois, and was published in the prestigious journal Nature Genetics.
In recent years, for unknown reasons there has been an increase in the prevalence of allergies in general and specifically in the skin, including atopic dermatitis (which is often called “asthma of the skin”). It had been thought that immune system malfunction was the cause of the growing problem. This notion resulted in numerous attempts to treat atopic dermatitis through varied strategies – all aimed at weakening immune system activity at the risk of often severe side effects that increased the risk of complications from infections. But more recently, abnormalities in the body’s immune system have been thought to occur in allergic diseases due to a primary defect inside the “skin barrier.”
This barrier is in fact a functional entity located in the upper layers of the skin; it separates us from our environment and makes sure essential nutrients and proteins are kept within the body, while unwanted intruders, including allergens, are prevented from entering. The functionality of the skin barrier has been shown to be dependent upon the presence within human cells of several proteins, such as filaggrin – whose absence is considered a major risk factor for atopic dermatitis.
Now, the international team of researchers report that key to the proper function of the barrier are desmosomes. Liat Samuelov, who co-headed the project with Ofer Sarig in Tel Aviv, commented: “Desmosomes are responsible for ensuring cell-cell adhesion within all layers of the skin. We found out that a critical component of the desmososmes called desmoglein 1 is missing in the skin of patients affected by a life-threatening form of allergic skin disease called SAM syndrome (Severe dermatitis, Allergy, and Metabolic wasting).
Sarig added: “The disease is caused by poorly functional bonds between cells located in the upper part of the skin.
This is apparently enough for foreign proteins to move across the skin barrier and elicit an exaggerated immune response. Even more interestingly, when we studied isolated cells from the patients, these were found to secrete numerous mediators of allergy.”
Their discovery thus questions the role of the immune system in allergic processes, with clear implications for the development of new treatments in atopic dermatitis, they said.
THERAPEUTIC POOP
We all know about organ transplants – but stool transplants to treat drug-resistant diarrhea in children? In its more extreme form, recurrent diarrhea can cause life-threatening colon inflammation, which is for some 14,000 deaths each year in the US alone, according to the country’s Centers for Disease Control and Prevention.
In fact, according to researchers at Johns Hopkins Children’s Center in Baltimore, the best hope yet for an effective treatment of childhood infections with the drug-resistant bacterium C. difficile may come straight from the gut.
Dr. Maria Oliva-Hemker, director of pediatric gastroenterology there, is launching a fecal transplantation program for patients with recurrent diarrhea. She says it is caused by a “wily pathogen that is increasingly impervious to drugs and a rapidly growing problem among children and adults.”
Over the past two decades, cases of antibiotic-resistant diarrhea have more than doubled, with nearly three million new infections each year, with up to a fourth of patients not responding to antibiotics, research shows. Most such cases, the researchers say, stemmed from infections with bacteria called C. difficile.
“Fecal transplantation – or the transfer of ‘good’ bacteria from the colon of one person into the colon of another – should be considered for all children with C. difficile infections who don’t respond to two standard courses of antibiotics,” said the Maryland researcher.
Studies in adults show that more than 90 percent of patients are cured following such therapy and, experts say, they have every reason to believe the numbers would be equally impressive in children.
“Antibiotics are lifesavers, but any time we give them to a patient to eradicate one pathogen, there’s collateral damage, in that along with the bad bacteria we wipe off some good organisms that help keep the complex workings of our gut in perfect balance,” Oliva-Hemker explained.
Such beneficial bacteria work by keeping rogue players in check, “so any shifts in gut environment – such as ones caused by antibiotics — can have dire consequences.
When good bacteria are killed off by antibiotics, the bad guys multiply causing an imbalance or “dysbiosis,” Oliva- Hemker said. Typically, gut infections caused by one antibiotic are treated with another one to eradicate the overgrowth of harmful pathogens, but drugs often fail to do so fully or permanently because they only treat part of the problem.
“When we administer an antibiotic to treat the C. difficile infection, we destroy some of the bad bacteria, but that does not address the other half of the problem — the loss of good bacteria that might have led to the infection to begin with, so we never truly restore the balance in the gut and often the diarrhea returns with a vengeance in a matter of weeks,” added Dr. Suchitra Hourigan, a pediatric gastroenterology fellow at Hopkins who has a special interest in fecal transplantation.
The concept is hardly new. The method originated with ancient Chinese healers who gave their diarrhea-ravaged patients “yellow soup,” a concoction of fecal matter and water. Thousands of years later, the delivery approach has evolved. Today, fecal transplants are often performed during a colonoscopy, and improvement can be seen in as little as two weeks, as beneficial bacteria start to repopulate the patient’s gut. Fecal donors, usually parents or relatives, are carefully screened for risks much like any blood donor, Hourigan says. The donor’s blood is tested for infectious pathogens, such as HIV and hepatitis C. People with autoimmune diseases or other chronic conditions, such diabetes or obesity, may not qualify as donors.
In a decade or so, Oliva-Hemker predicts, scientists would be able to design the perfect fecal concoction in a lab, obviating the need for fecal transplants.
“In less than a decade, we’ll have lab-cooked poop that we can administer to restore balance in the guts of people with a wide array of conditions caused by the imbalance between good and bad germs.”