Rheumatoid arthritis: Scientists stop tissue damage

People with rheumatoid arthritis have a faulty mechanism in their immune system. Repairing it could stop the inflammation and tissue damage that the disease inflicts on the synovial tissue that lines and protects the joints.

These were the conclusions that scientists at Stanford University School of Medicine in California came to after demonstrating how an experimental compound was able to repair the faulty mechanism in a mouse model of rheumatoid arthritis (RA).

study that now appears in the journal Nature Immunology reports how researchers identified the fault in helper T cells of the immune system and how it changes their behavior.

Prof. Cornelia M. Weyand, who is chief of immunology and rheumatology, is the senior author of the study.

She and her colleagues explain that once the faulty helper T cells enter synovial tissue, they summon aggressive immune cells and trigger inflammation and destruction of normal synovial cells.

They ran tests on mice with grafts of human synovial tissue that had become inflamed following injections of helper T cells from humans with RA.

The experimental compound shut down the faulty mechanism in the human helper T cells and reduced their inflammatory effects in the mice.

The team hopes to start human clinical trials of the compound or one of its derivatives soon.

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Rheumatoid arthritis and the immune system

RA is a disease that causes swelling, stiffness, and pain in the joints. Other symptoms include nausea, tiredness, and occasional fevers.

The disease affects around 1 in 100 people. Although it can strike at any age, it is more common in older people. Also, women are more likely to develop it than men.

Experts are not exactly sure what causes RA. They have concluded, however, that it is an autoimmune disease, whereby the immune system attacks healthy tissue in the same way as it attacks disease bacteria and viruses.

In RA, the immune system repeatedly attacks the synovia, which is the soft lining of the joints that stops bones from chafing each other.

Destruction of the synovia also occurs in osteoarthritis. However, in this case, the damage arises from the wear and tear that accompanies aging.

The inflammation that occurs in RA can also damage other parts of the body. It can double the risk of heart disease, for instance.

Prof. Weyand remarks that while existing drugs can relieve the symptoms of RA, they do not rectify the errant immune cells.

She and her colleagues learned that faulty helper T cells divert their internal cell resources from making energy to producing “an army of inflammatory offspring.”

“This cellular army,” explains Prof. Weyand, “exits the lymph nodes, makes its way to synovial tissues, takes up residence there, and instigates the inflammatory damage that’s the hallmark of rheumatoid arthritis.”

Faulty cells divert use of glucose

The recent study builds on previous work in which the team observed certain differences in the helper T cells of healthy people and of those with RA.

For example, they noticed that in RA, helper T cells have low levels of ATP, which is a molecule that all cell processes use as units of energy.

However, in spite of having low levels of ATP, the aberrant cells send glucose to help make new cell materials instead of producing more ATP. Making new cell materials just causes further damage.

In healthy people, helper T cells do not behave like this. This is because when they sense low levels of ATP, they divert glucose toward making more ATP.

The mechanism that helps T cells sense low ATP relies on a molecule called AMPK, which monitors the ratio of ATP and two of the main products that it breaks down into.

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When the ratio of ATP to these breakdown products falls below a certain level, AMPK triggers a switch that diverts glucose from making cell materials to making ATP fuel.

“When your house is cold,” Prof. Weyand explains, “you need to throw your logs into your fireplace, not use them to build a new house in your backyard.”

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