April 2, 2007

Minnesota Partnership Researchers Discover Disease 'Fingerprint'
Interferon signature in dermatomyositis

MINNEAPOLIS/ROCHESTER, Minn. -- A Minnesota Partnership research team has discovered a 'fingerprint' or signature pattern in the blood associated with the autoimmune disease dermatomyositis. Physicians could use this fingerprint as an alternative diagnostic tool, rather than more invasive muscle biopsy, according to the researchers. The findings appear in the current issue of the journal Molecular Medicine.

Juvenile and adult dermatomyositis are two of the less common autoimmune diseases belonging to the group of idiopathic inflammatory myopathies. These are conditions in which the body's immune system overreacts in some way to attack some part of the body and the direct cause is not clear. Primary symptoms are inflammation around blood vessels in skin and muscle tissues, along with a debilitating weakness that in some cases may be fatal. The disease is often accompanied by a rash, especially near the eyes.

"This is a wonderful and easy way to monitor patients," says Ann Reed, M.D., Mayo Clinic rheumatologist and co-investigator of the study. "This research matters for people who are asking questions such as: 'Is my disease still active? Is it OK to stop treatment? How much longer should I continue with medication?'"

RNA (ribonucleic acid) carries messages that direct the body's functions. Researchers looked at RNA expressions to determine whether RNA is active. RNA expressions -- specialized proteins -- indicate which genes are 'turned on' and which genes can be 'turned off.' "Looking at proteins and RNA is like looking at a fingerprint," says Dr. Reed.

"With this fingerprint, you can look at thousands of factors, not just one at a time. It opens the door to a much broader picture of the condition," says Timothy Behrens, M.D., co-investigator from the University of Minnesota.

Twelve patients, ten adults with dermatomyositis and two with the juvenile condition, were evaluated. Clinical data were collected for each patient, including duration of disease, current disease activity, muscle biopsy, and medications they were taking. Investigators looked at the interferon present (type l IFN-regulated transcripts). Interferon is a product of the cellular autoimmune system usually produced in reaction to a virus. Analysis revealed a significant interferon signature present in most dermatomyositis patients studied. Levels of type l IFN-regulated proteins were also elevated in dermatomyositis serum samples. Both the transcript and serum protein IFN signatures were associated with disease, suggesting that the IFN signature may serve as a useful marker for dermatomyositis disease activity in both adults and children. The IFN fingerprint also suggests the disease may be initiated by a virus.

Emerging data from other studies suggest that cells from affected muscle tissue carry distinct immune 'fingerprints' which may be useful for monitoring disease status and may provide new targets for treatments. Researchers say the goal is to personalize treatment and use this 'fingerprint' to determine what kind of medicine might work best for the patient. They say their next step is to validate the results with a larger population.

Patient studies and protein evaluations were conducted at Mayo Clinic. The gene array studies and expertise for interpreting the RNA was provided by the University of Minnesota. This Partnership work was completed within a year.

Other collaborators include first author Emily Baechler, M.D.; Jason Bauer; Catherine Slattery; Ward Ortmann; Karl Espe; and Jill Novitzke, all of the University of Minnesota; Steve Ytterberg, M.D., Mayo Clinic; and Peter Gregersen, M.D., Feinstein Institute for Medical Research, North Shore Long Island Jewish Research Institute.

Funding was provided by the Minnesota Partnership and by grants and contracts from the National Institutes of Health. The Minnesota Partnership for Biotechnology and Medical Genomics is a collaborative research initiative among Mayo Clinic, the University of Minnesota and the state of Minnesota, dedicated to advancing health and improving Minnesota's economy.

Read more about the research team.

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