May Be Arthritis Culprit
BOSTON (Reuters Health) - A Harvard researcher has proposed a
totally new offender in the abnormal immune system attack that
leads to rheumatoid arthritis: naturally-occurring carbohydrates.
These carbs aren't starches or sugars, but more complex molecules
known as glycosaminoglycans (GAGs), which compose much of the
body's connective tissue and are also found in the fluid within
Rheumatoid arthritis occurs, according to Dr. Julia Ying Wang's
theory, because immune system cells called antibodies target GAGs,
binding to them and then accumulating in the joints, leading to
pain and inflammation.
Rheumatoid arthritis is a chronic disease in which the body's
own immune system attacks the tissue lining the joints. It is
more common in women, tends to strike between the ages of 36 and
50, and results in chronic destruction and deformity of the joints.
The Harvard Medical School assistant professor reported her
findings here Wednesday at the American Chemical Society's annual
meeting. The research, she said, offers the prospect of a treatment
for this debilitating disease.
Wang has encountered some resistance to her findings, she noted.
Proteins and fragments of protein called peptides are conventionally
thought of as immune system triggers, but carbohydrates are rarely
considered to play a role in immune reactions.
The Harvard researcher decided to study GAGs' role in rheumatoid
arthritis because the carbohydrates are a major component of joint
tissue, and because people with the disease are known to have
higher levels of certain GAGs in their joints.
To investigate, Wang and her colleagues injected mice with GAGs.
The mice, they found, developed chronic rheumatoid arthritis-like
symptoms, including inflammation and swelling of the membranes
lining the joints, the tissue surrounding the tendons, and the
skin. Some animals developed erosion of the bone.
Antibodies were binding to GAGs, she and her colleagues found,
and accumulating in the animals' joints.
Wang and her colleagues have since found GAG antibodies in tissue
from rheumatoid arthritis patients. This is the first time, she
notes, that such antibodies have been seen in animals or humans.
These antibodies may be part of the body's response to bacterial
infection, Wang said. Many bacteria, including the bug responsible
for flesh-eating disease, carry GAG-like molecules on their surface,
and the body's own immune cells also secrete GAG when fighting
This can prime immune cells to mistakenly target the GAGs that
make up the body's own tissues.
Wang is now testing molecules with the potential of blocking
the binding of GAG antibodies to GAG. Drugs based on such molecules,
she said, could offer a treatment for rheumatoid arthritis. And
the test she and her colleagues developed to identify the GAG
antibodies could also be used as a screening tool, she added,
to determine if a patient is at risk of developing the disease.
Reference Source 89