[PHNUTR-L] Joslin: Scientists Exploring Inflammation in Rheumatoid Arthritis Make Unexpected Discovery

[Kathrynne Holden, MS, RD]

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Scientists Exploring Inflammation in Rheumatoid Arthritis Make 
Unexpected Discovery That One Day May Lead to New Treatments
http://www.joslin.org/1083_3262.asp

BOSTON — February 15, 2006 — What makes joints in people with rheumatoid 
arthritis, and related conditions like Lyme disease or lupus, so 
susceptible to attack by the body’s immune system, leading to painful 
flare-ups and deterioration? The answer may surprise you.

The answer did surprise investigators at Joslin Diabetes Center and 
Massachusetts General Hospital (MGH) in Boston, who gained a novel 
insight into this question in a recent collaborative study. Their report 
appeared in the January 29 online issue of Nature Immunology, and is 
scheduled to appear in the February print edition.

Working with an animal model of rheumatoid arthritis, the researchers 
discovered that histamine, a small molecule usually associated with 
asthma and allergy, is produced as part of the inflammatory process 
during the development of arthritis. Histamine made the blood vessels 
surrounding the joints especially vulnerable to leakage, and thereby 
rendered the joints more susceptible to inflammatory attack. The 
researchers believe that this is true not only in rheumatoid arthritis, 
but perhaps also in other autoimmune conditions with which arthritis is 
associated, such as lupus, and in some infectious diseases, like Lyme 
disease.

“For patients with rheumatoid arthritis, these new findings raise the 
possibility that medications designed to prevent the blood vessels from 
becoming leaky might one day be used to delay the onset of arthritis or 
to prevent flare-ups of disease,” said Christophe Benoist, M.D., Ph.D., 
who led the study together with Diane Mathis, Ph.D., and Ralph 
Weissleder, M.D., Ph.D. Drs. Mathis and Benoist head Joslin’s Section on 
Immunology and Immunogenetics, hold the William T. Young Chair in 
Diabetes Research at Joslin, and are Professors of Medicine at Harvard 
Medical School. Dr. Weissleder heads the Center for Molecular Imaging 
Research at MGH and is a Professor of Radiology at Harvard Medical School.

While the Joslin lab focuses its work on type 1 diabetes, arthritis has 
several related mechanisms. Like type 1 diabetes, rheumatoid arthritis 
is an autoimmune disease, in which the body’s immune system attacks 
itself as though fighting off an enemy invader.

The Arthritis Foundation reports the number of Americans with arthritis 
or chronic joint symptoms has risen from 35 million to 66 million 
(nearly 1 in 3 adults) in 2005. Rheumatoid arthritis (RA) is a chronic 
autoimmune disease characterized by inflammation of the lining, or 
synovium, of the joints. It is one of the most severe forms of arthritis 
and can lead to long-term joint damage, resulting in chronic pain, loss 
of function and disability. RA affects 1 percent of the U.S. population 
or 2.1 million Americans, mostly women.

In their study, the researchers developed a new microscopic imaging 
method to visualize changes in blood vessel permeability in anesthetized 
mice. Within minutes following the delivery of arthritis-causing 
antibodies to the mice, the blood vessels around the joints became 
temporarily leaky, making it easier for the antibodies to enter the 
joint spaces. There, the antibodies set off a cascade of inflammatory 
cells and molecules, eventually resulting in arthritis.

“The big surprise was that the other blood vessels throughout the body 
did not become leaky, suggesting that there is something special about 
the vessels in the joints,” says Bryce Binstadt, M.D., Ph.D., of Joslin 
and Children’s Hospital Boston, lead author on the study.

In trying to identify the special feature, the investigators made the 
even more unexpected discovery that histamine was responsible for the 
joint blood vessel leakiness — in fact, the researchers could mimic the 
effect of the antibodies on blood vessel leakiness by just injecting 
histamine.

Other researchers participating in the study included Pratik R. Patel, 
Herlen Alencar, M.D., and Umar Mahmood, M.D., Ph.D., of the Center for 
Molecular Imaging Research, Massachusetts General Hospital; Peter A. 
Nigrovic, M.D., of Children’s Hospital and Brigham and Women’s Hospital, 
Boston; and David M. Lee, M.D., Ph.D., of Brigham and Women’s Hospital.

This work was funded by grants from the National Institutes of Health. 
Dr. Binstadt is supported by a Pfizer Postdoctoral Fellowship in 
Rheumatology/Immunology.


The image above at left shows normal blood vessels in a mouse paw. Five 
minutes after receiving arthritis-causing antibodies, the blood vessels 
become leaky, as shown at right.
Photo by Bryce Binstadt, M.D., Ph.D., and Pratik Patel
Courtesy Joslin Diabetes Center and Massachusetts General Hospital

About Joslin Diabetes Center

Joslin Diabetes Center, dedicated to conquering diabetes in all of its 
forms, is the global leader in diabetes research, care and education. 
Founded in 1898, Joslin is an independent nonprofit institution 
affiliated with Harvard Medical School. Joslin research is a team of 
more than 300 people at the forefront of discovery aimed at preventing 
and curing diabetes. Joslin Clinic, affiliated with Beth Israel 
Deaconess Medical Center in Boston, the nationwide network of Joslin 
Affiliated Programs, and the hundreds of Joslin educational programs 
offered each year for clinicians, researchers and patients, enable 
Joslin to develop, implement and share innovations that immeasurably 
improve the lives of people with diabetes. As a nonprofit, Joslin 
benefits from the generosity of donors in advancing its mission. For 
more information on Joslin, call 1-800-JOSLIN-1 or visit 
http://www.joslin.org/.

About Massachusetts General Hospital

Massachusetts General Hospital, established in 1811, is the original and 
largest teaching hospital of Harvard Medical School. The MGH conducts 
the largest hospital-based research program in the United States, with 
an annual research budget of nearly $500 million and major research 
centers in AIDS, cardiovascular research, cancer, cutaneous biology, 
medical imaging, neurodegenerative disorders, transplantation biology 
and photomedicine. In 1994, MGH and Brigham and Women’s Hospital joined 
to form Partners HealthCare System, an integrated health care delivery 
system comprising the two academic medical centers, specialty and 
community hospitals, a network of physician groups, and nonacute and 
home health services.  For more information, visit 
http://www.massgeneral.org/.
-- 
Kathrynne Holden, MS, RD < fivestar at nutritionucanlivewith.com >
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