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Culprit responsible for severe systemic scleroderma complications in African-Americans found

Researchers say 3 proteins linked to worse outcomes are found more often in blacks than Caucasians with a common form of scleroderma

A new analysis finds that compared to Caucasians, African-Americans with systemic scleroderma have more antibodies in the blood that are linked to severe complications and an increased likelihood of death. They say this finding, published today in Arthritis & Rheumatism, suggests physicians can use these disease markers to screen and treat scleroderma patients proactively.

For the study, Georgetown University Medical Center (GUMC) teamed up with researchers from the University of Pittsburgh School of Medicine to examine 35 years of data collected about the autoimmune disease.

According to the Scleroderma Foundation, there are an estimated 300,000 people in the United States who have scleroderma and about one third of them have the systemic form. While both localized and systemic scleroderma cause hardening of the skin, systemic scleroderma also causes damage to the blood vessels, muscles, and internal organs. Scleroderma occurs when a person's immune system mistakenly attacks and destroys healthy body tissue.

Previous studies suggest that systemic scleroderma is more common, occurs at a younger age and is more severe in African-Americans than Caucasians. Researchers set out to examine if there was a difference in antibodies found in the blood to see if that might explain why African-Americans with the disease often do worse.

Virginia D. Steen, M.D., professor of medicine at GUMC, and her colleagues at Pittsburgh analyzed data from the Pittsburgh Scleroderma Database. Steen helped develop the database,which includes demographic, clinical, autoantibody, organ involvement and survival information for 203 African-American and 2945 Caucasian scleroderma patients seen at the University of Pittsburgh Medical Center between 1972 and 2007.

"Our findings show that African-Americans were more likely to have certain antibodies linked to severe complications such as severe pulmonary fibrosis and gastrointestinal involvement," explains Steen. "These complications tend to be the culprit for people who die from severe cases of scleroderma."

The findings show that African-Americans had higher frequencies of certain scleroderma specific autoantibodies compared to Caucasians: anti-U3-RNP (40 percent vs. 2 percent), U1-RNP (16 percent vs. 7 percent) and anti-topoisomerase (27 percent vs. 21 percent). Anti-topoisomerase auto-antibodies in scleroderma are associated with a higher incidence of pulmonary fibrosis (scarring of the lungs) and greater disease severity, and in this study, African-American patients with this antibody had more frequent and more severe fibrosis than the Caucasians with this antibody.

Pulmonary fibrosis was also more severe in African-American patients with anti-U1 RNP auto-antibodies compared to Caucasian patients with this antibody but a difference in survival between the races was not apparent. Researchers determined that the auto-antibody anti-U3 RNP was linked to more severe gastrointestinal involvement in blacks compared to Caucasians.

"This information can help empower patients and their doctors to act more aggressively, if appropriate, when the person with scleroderma has these antibodies associated with worse outcomes," concludes Steen. "We believe early aggressive intervention will improve outcomes."

In addition to Steen, authors include Robyn T. Domsic, Mary Lucas, Noreen Fertig, Thomas A. Medsger, Jr., of the University of Pittsburgh School of Medicine. Funding for the database has been received from the American College of Rheumatology, Scleroderma Foundation and numerous other grants from foundations and organizations. Steen and her co-authors report having no personal financial interests related to the study.

About Georgetown University Medical Center

Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization (BGRO), which accounts for the majority of externally funded research at GUMC including a Clinical Translation and Science Award from the National Institutes of Health. In fiscal year 2010-11, GUMC accounted for 85 percent of the university's sponsored research funding.

Karen Mallet | EurekAlert!
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