1. Originally Released: May 1, 2000
Contact: Ellen Beth Levitt, eblev...@umm.edu, 410-328-8919
RESEARCHERS FIND INCREASED ZONULIN LEVELS AMONG CELIAC DISEASE
PATIENTS
Researchers at the University of Maryland School of Medicine have
found that the human protein zonulin, which regulates the permeability
of the intestine, is at increased levels during the acute phase of
celiac disease. The discovery suggests that increased levels of
zonulin are a contributing factor to the development of celiac disease
and other autoimmune disorders such as insulin dependent diabetes,
multiple sclerosis, and rheumatoid arthritis. The findings are
published in the April 29 issue of the journal Lancet.
"Zonulin works like the traffic conductor or the gatekeeper of our
body's tissues," says lead author Alessio Fasano, M.D., professor of
pediatrics and physiology at the University of Maryland School of
Medicine, and director of Pediatric Gastroenterology and Nutrition at
the University of Maryland Hospital for Children. "Our largest gateway
is the intestine with its billions of cells. Zonulin opens the spaces
between cells allowing some substances to pass through while keeping
harmful bacteria and toxins out," explains Dr. Fasano.
Earlier research conducted by Dr. Fasano discovered that zonulin is
also involved in the regulation of the impenetrable barrier between
the blood stream and the brain, known as the blood-brain barrier.
Celiac disease offered Dr. Fasano and his team a unique model for
understanding the dynamic interaction between zonulin and the immune
system. Celiac disease is a genetic disorder that affects one out of
every 300 people in Europe, but its prevalence in the United States is
not fully known. People who suffer from the disorder are unable to eat
foods that contain the protein gluten, which is found in wheat and
other grains. The gluten sets off a reaction that can cause diarrhea,
abdominal pain, malabsorption of nutrients, and other gastrointestinal
problems. Celiac disease can be easily treated by avoiding foods with
gluten.
With celiac disease, the body reacts to gluten by creating antibodies
that attack the intestine and cause severe damage over time. Unlike
other autoimmune disorders, scientists also know that celiac disease
is triggered by a specific antigen, which is the protein gluten.
Celiac disease is also known to cause increased permeability of the
intestine. In addition, many people who suffer from celiac disease
also suffer from other autoimmune disorders.
The research team examined the intestinal tissue of seven people with
celiac disease, and six patients without the disease. Patients with
active celiac disease showed higher levels of zonulin and anti-zonulin
antibodies compared to non-celiac patients and patients in remission,
who were eating a gluten-free diet.
"With celiac disease, we could never understand how a big protein like
gluten was getting through to the immune system. Now we have the
answer," explains Dr. Fasano. "People with celiac have an increased
level of zonulin, which opens the junctions between the cells. In
essence, the gateways are stuck open, allowing gluten and other
allergens to pass. Once these allergens get into the immune system,
they are attacked by the antibodies," adds Dr. Fasano.
"I believe that zonulin plays a critical role in the modulation of our
immune system. For some reason, the zonulin levels go out of whack,
and that leads to autoimmune disease," explains Fasano.
Dr. Fasano adds that more research is needed. He is currently
conducting experiments with diabetic rats. Preliminary results from
his experiments show that insulin dependent diabetes occurs in lab
rats about three to four weeks after increased intestinal
permeability. The researchers believe the increased intestinal
permeability is associated with increased levels of zonulin.
"We are at the threshold of exciting discoveries in this field," says
Dr. Fasano. "We now have a new way of looking at our cells. Our cells
are not stacked together like bricks. They are a dynamic field, which
is constantly in flux."
