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Scientists Uncover Marker Of Autoimmune Disease Activity

Date:
September 17, 1998
Source:
University Of Texas Southwestern Medical Center At Dallas
Summary:
UT Southwestern Medical Center at Dallas researchers have uncovered what they believe is a marker of autoimmune disease activity in patients with lupus and rheumatoid arthritis, which may one day enable doctors and patients to predict disease flare-ups.

DALLAS--September 15, 1998--UT Southwestern Medical Center at Dallas researchers have uncovered what they believe is a marker of autoimmune disease activity in patients with lupus and rheumatoid arthritis, which may one day enable doctors and patients to predict disease flare-ups.

In today's issue of the Journal of Clinical Investigation, Dr. Mark Siegelman, associate professor of pathology at UT Southwestern, and colleagues described the correlation of disease flare-ups in pediatric patients with lupus and rheumatoid arthritis with the level of activated CD44 (the marker) in circulating blood. The activated form of CD44, a cell surface molecule induced on a small subpopulation of white blood cells called T-lymphocytes (T-cells) during immune reactions, was measurable only in patients who were experiencing an exacerbation of their condition.

Dr. Pila Estess, UT Southwestern assistant professor of pathology and a co-author of the study, envisions the day when patients with autoimmune diseases or their physicians will be able to monitor blood levels for activated CD44 much the same way that diabetes patients monitor their blood-sugar levels.

"T-cells are thought to be the cells that start and perpetuate autoimmune disease," said Siegelman. "In our study, every time there was an exacerbation, there was another wave in the blood of T-cells with activated CD44 on their surface. The implication is that these cells may initiate the autoimmune exacerbations."

Activated CD44 T-cells have the ability to bind to a specific molecule called hyaluronan (HA) induced on the inner surface of the blood vessels near or in the inflammatory site. These particular T-cells repeatedly bind to HA as they roll along the blood vessel wall. The result of this "rolling" is a slowing down of the T-cells so that they can bind more firmly to other adhesion molecules and move out through the blood vessel to the site of inflammation, where they cause further injury.

Previous work by these investigators showed that in mice the migration of T-cells into an inflammatory site (extravasation) was dependent on this interaction of CD44 with HA (Science 278:672, 1997). They proposed that in humans activated CD44 initiates extravasation of T-cells at sites of inflammation. This paper supports that proposal by clearly showing that circulating blood only from patients with disease flare-ups contains activated CD44 T-cells that undergo "rolling."

"There has never been a reliable cell surface marker that correlates with an autoimmune exacerbation," said Siegelman. "Regarding therapeutic treatment, if these are truly the T-cells that enter the tissue and initiate damage, you should be able to intervene in the disease process by directly getting in the way of the CD44-HA interaction, thereby preventing injury. Currently we are trying to design molecules that block the CD44-HA connection." Other UT Southwestern investigators involved in the study were lead author Dr. Heather DeGrendele, a postdoctoral fellow in pathology, and Dr. Virginia Pascual, assistant professor of pediatrics.

Grants from the National Institutes of Health, the Welch Foundation, the Arthritis Foundation and the Texas Higher Education Coordinating Board helped support the research.


Story Source:

The above story is based on materials provided by University Of Texas Southwestern Medical Center At Dallas. Note: Materials may be edited for content and length.


Cite This Page:

University Of Texas Southwestern Medical Center At Dallas. "Scientists Uncover Marker Of Autoimmune Disease Activity." ScienceDaily. ScienceDaily, 17 September 1998. <www.sciencedaily.com/releases/1998/09/980917080541.htm>.
University Of Texas Southwestern Medical Center At Dallas. (1998, September 17). Scientists Uncover Marker Of Autoimmune Disease Activity. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/1998/09/980917080541.htm
University Of Texas Southwestern Medical Center At Dallas. "Scientists Uncover Marker Of Autoimmune Disease Activity." ScienceDaily. www.sciencedaily.com/releases/1998/09/980917080541.htm (accessed July 28, 2014).

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