New technique holds promise for treatment of rheumatoid arthritis
By Leon Gettler
February 15, 2013
A team of scientists at Boston's Dana-Farber Cancer Institute has developed a new technique to treat autoimmune diseases such as rheumatoid arthritis. The approach, which is based on the infusion of cells that regulate immune responses, has been demonstrated to to be effective in mice, even weeks after the disease was initiated.
Characterized by joint inflammation, rheumatoid arthritis is one of many different autonomous diseases. It is estimated that 50 million Americans suffer from autoimmune disorders which also include lupus, type 1 diabetes, multiple sclerosis and celiac disease. At least 100 different autoimmune diseases have been identified.
The human immune system normally, attacks and destroys infections, viruses, parasites, and other foreign "invaders." But in autoimmune disorders, parts of the immune system attack the body’s healthy cells and tissues. These parts of the immune system fail to recognize "self" identifying tags on the body's cells.
In this new research, the mice were first injected with a protein that triggered the arthritis-causing autoimmune reaction. The scientists then infused CD8 T regulatory, or CD8 Treg cells, which play a key role turning off an immune response when it’s no longer needed after the body has repelled viral or bacterial invaders.
The scientists injected peptide antigens to expand the pool of CD8 Tregs in each mouse, rather than infusing them from outside. They found that CD8 Tregs recognized and eliminated those parts of the immune system, called CD4 T helper cells, that mistakenly respond to the “self” markers on healthy cells and become chronically over-activated, spurring a continuous attack by antibodies on the body’s tissues.
When combined with methotrexate, a commonly used drug for treating rheumatoid arthritis, the researchers found it slowed the disease down significantly.
This “upstream”treatment – where a cell is used to block other cells that spur an attack by antibodies on the body’s tissues – is different from the way rheumatoid arthritis is currently treated with inflammation-reducing drugs like corticosterioids. Suxh "downstream" approaches block secreted chemicals called cytokines which carry out the attacks, but they can also result in severe side effects like high blood pressure, weight gain and increased risk of infection.
“We found we could almost completely inhibit the disease in this setting," says Harvey Cantor, MD, chair of the Department of Cancer Immunology and AIDS at Dana-Farber. "We believe that targeting the CD4 T cells that initiate this cascade may be a more effective approach to rheumatoid arthritis therapy."
The researchers will now test mice carrying human immune cells that provoke an autoimmune response. The collagen-induced arthritis in the mice is seen as similar to rheumatoid arthritis in humans because they share symptoms including breach of self-tolerance, generation of auto antibodies, inflammatory changes in multiple joints, and erosion of bone and cartilage.
The findings were published in Journal of Clinical Investigation
Source: Dana-Farber Cancer Institute
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