The Complement System and Rheumatoid Arthritis

Autoimmune diseases like rheumatoid arthritis are one of the few remaining classes of condition where little can be done for many sufferers at this time, and where researchers still know comparatively little about specific causative mechanisms. The most effective treatments are based on suppressing the immune system rather than addressing root causes, and even those are hit and miss.

Meanwhile here is one of the signs that this may all be changing in the years ahead, as modern tools allow a greater understanding and ability to manipulate facets of the immune system:

"We found that fat in the knee joints secretes a protein called pro-factor D which gives rise to another protein known as factor D that is linked to arthritis. Without factor D, mice cannot get rheumatoid arthritis." [With] the discovery of pro-factor D in mice with rheumatoid arthritis, [researchers are] working on gene therapies to eliminate the protein in localized areas. However, these findings still need to be extended to humans. "We are looking at vaccines, drugs or inhibitors to stop the local secretion of pro-factor D in the mouse. Our goal would be to stop the disease before it progresses and leads to joint destruction."

Factor D is part of the complement system, a complex array of over 40 proteins that help the body fight off bacteria and other pathogens. In studies with arthritic mice, [researchers] previously found that the complement pathway involving factor D made the mice susceptible to inflammatory arthritis. [Removing] factor D, rather than the entire complement system, achieves the same result without compromising other parts of the system that can fight infection.

While it's theoretically possible to destroy the entire complement system in humans to prevent arthritis, it eventually returns along with a renewed risk of contracting the disease. In the meantime, patients can get infections and other complications because they lack this critical part of the immune system. "The complement system is both friend and foe. We believe we can shut down one part of the complement system that triggers disease without shutting down the rest. If so, we will be making a major stride toward treating and perhaps even curing rheumatoid arthritis."



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