How Does Rheumatoid Arthritis Attack The Whole Body?

One of the mysteries in the understanding of a complicated disease like rheumatoid arthritis is… how does it attack so many joints? What causes it to spread?

Rheumatoid arthritis is a chronic, systemic, autoimmune condition that usually starts in a single joint but then spreads to involve multiple joints. The hallmark of the disease is its symmetrical joint involvement. Also, because internal organs may be affected, it is a disease that carries with it substantial morbidity (complications) as well as mortality (death).

Rheumatoid arthritis is very different from the other common form of arthritis, osteoarthritis, which is basically a wear and tear problem localized to weight-bearing joints. Osteoarthritis does not produce the destructive changes that are characteristic of rheumatoid disease.

Recent research has provided tantalizing evidence as to how rheumatoid arthritis spreads.

Researchers at Justus-Liebig University in Bad Nauheim, Germany recently published the results of their work in Nature Medicine demonstrating the critical role of rheumatoid arthritis synovial fibroblasts (RASFs) in the spread of the disease.

Fibroblasts are a type of cell that is primarily involved in the wound healing process. They are responsible for the laying down of connective tissue. However, when turned on in a particular fashion, they morph from Dr. Jeckyll into Mr Hyde.

These “turned-on” fibroblasts, now known as “rheumatoid arthritis synovial fibroblasts”, are present in abundance in the synovium- the lining of the joint. These RASFs become very destructive and are felt to be one of the major culprits responsible for the damage to cartilage found in rheumatoid arthritis.

To elucidate the mechanism by which RASFs could spread arthritis from joint to joint, lead author Elena Neumann and her colleagues took human cartilage and implanted it under the skin of mice genetically engineered not to reject tissue from a different species. The implantations were done in the flanks.

On one flank, the mice received healthy, normal human cartilage; on the other, they received cartilage loaded with human RASFs.
A control group of mice who received normal healthy cartilage in both flanks showed minimal damage, as did mice that received implants of fibroblasts from patients with osteoarthritis.

Another striking discovery occurred when the researchers sacrificed the mice and examined the spleens. The mice which developed rheumatoid arthritis had spleens packed with RASFs. The spleen is the major organ responsible for filtering blood. The fact that RASFs are found in such abundance in the spleens of the rheumatoid arthritis mice provides strong evidence that RASFs travel through the blood stream to do their damage rather than just secrete chemicals that go into the blood stream.

Apparently RASFs can travel via the blood stream and then leave by crawling through the spaces between cells that form the lining of the blood vessels to invade other joints and other organ systems.

When the researchers look at the joints of the sacrificed mice, they didn’t find RASFs. They hypothesized that it takes time for the RASFs to travel to other joints and can only enter cartilage if there is already some minor damage. This would explain why it often takes many months for rheumatoid arthritis to spread.

The scientific findings have therapeutic implications since treatments designed to prevent RASFs from entering the bloodstream, traveling through the blood stream, or leaving the blood stream to attack healthy tissue could potentially prevent the spread of rheumatoid arthritis.

[Editor\’s note: I personally think this is one of the most exciting bits of news in a long time and the authors should be commended for such fine work.]

Author Bio: Nathan Wei, MD FACP FACR is a board-certified rheumatologist and nationally known arthritis expert. For more info: Arthritis Treatment and Arthritis Treatment Center

Category: Medicines and Remedies
Keywords: arthritis treatment, rheumatoid arthritis, synovial fibroblasts

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