Spotlight on Research for 2004

September 2004 (historical)

Synthetic Peptide May Help Correct Damaging Immune Response in RA

For the 2.1 million Americans with rheumatoid arthritis (RA) - a disease in which the body's immune system attacks and damages joint tissues - treatment often involves strong drugs to suppress the immune system. While these drugs may be effective at keeping the disease under control, they can suppress the immune system too much, leaving the body vulnerable to infection.

Now, scientists supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases believe they have found a potential treatment to suppress the abnormal, self-directed immune response that is responsible for RA without hampering the body's ability to fight bacteria and viruses.

The treatment, which the researchers describe in a recent issue of the Proceedings of the National Academy of Sciences, is a synthetic peptide - a chain of amino acids - called dnaJP1.

Previously, researchers had found that in rheumatoid arthritis, the immune system is confused by a sequence of amino acids called human leukocyte antigen (HLA) produced on cells' surfaces during an immune response. In approximately 70 percent of RA patients, HLA shares a specific, characteristic sequence of amino acids.

In healthy people, HLA works to dampen the body's immune response and help keep it under control, says Salvatore Albani, M.D., professor of medicine and pediatrics at the University of California, San Diego. But in RA, the antigen fails to work properly, allowing an over-zealous immune response to cause damage. To help prevent that damaging response, Dr. Albani and his colleagues looked to a protein called dnaJ that the body uses to initiate the response. A section of that protein - the dnaJP1 peptide - has the same characteristic amino acid sequence as that found in RA patients. By giving patients a synthetic version of the dnaJP1 peptide, the researchers suspected they could reeducate the immune system to tolerate this specific amino acid chain instead of seeing it as foreign and attacking it.

In an initial study of 15 people, those suspicions proved correct. Blood tests showed that the drug had successfully trained the immune system to behave as it should. Though the initial study did not assess patient's symptoms, a new larger study will. The new study involves testing the peptide in 160 people. Participants receive either the peptide or a placebo and undergo blood tests to evaluate the drug's effect on the immune system and physical exams to determine if changes in the immune system result in a reduction in symptoms. The study is scheduled for completion later this year.

The National Institute of Allergy and Infectious Diseases, the Royal Netherlands Academy of Arts and Sciences, and the Dutch Organization for Scientific Research also helped fund this study.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov

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Prakken BJ, et al. Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis. PNAS 2004:101:4228-4233.