| Immunology 101: Pathways to a Cure<O:P> - From the Arthritis Research 9/03 - Full Article</O:P> Basic research about the role of the immune system in arthritis may seem dry and hard to understand, but as shared by several conference presenters, insights gained from such research are paving the way for innovative therapies to slow down and perhaps even stop disease progression. Death for T and B cells<O:P> <O:P>
The immune system is normally tightly controlled so that it is only deployed in response to foreign invaders. But sometimes, the system breaks down and mistakenly attacks the body’s own cells and organs. For instance, some immune cells called T cells attack the joint lining in rheumatoid arthritis (RA), while B cells create damaging proteins that are common in lupus. Scientists are making significant progress in determining how best to seek out and destroy just these harmful immune cells while leaving other parts of the body’s disease fighting system intact.<O:P> </O:P>
John Looney, MD, of the University of Rochester, reported that several different drugs directed at B cells or T cell-B cell interactions are now being tested in clinical trials. At this time, the best studied B cell specific agent is rituximab which is directed at a subset of B cells with a marker called CD20. A large recent clinical trial demonstrated marked improvement in patients with RA who were treated with rituximab, and Dr. Looney's own study of rituximab in patients with lupus suggested that this may be a useful drug in lupus as well.
Philippa Marrack, PhD, an investigator at the National Jewish Medical and Research Center in Denver, described the many checks and balances normally in place to get rid of harmful T cells. For example, researchers have identified a population of cells called regulatory cells that are designed to immobilize any T cells that are capable of attacking self-tissues. A better understanding of how to switch these cells on will help guide the design of drugs to enhance the body's natural self-protective mechanisms.</O:P> What's the relevance to people with arthritis? Therapeutic agents that selectively remove only those immune cells involved in the harmful immune response in diseases such as RA and lupus have obvious appeal. Not only could such targeted therapy help avoid many of the side effects seen with non-specific drugs, but it also has the potential of essentially turning off the underlying disease process, leading to a remission or even cure.</O:P> Taking the “Toll Road”: Your Frontline Defense<O:P>
Much of the research conducted on diseases such as RA has focused on one arm of the body's defense system called the adaptive immune response, which provides highly specific antibodies to block foreign invaders. As described in presentations by Arthur M. Krieg, MD (Coley Pharmaceutical Group, Wellesley MA) and Maripat Corr, MD, from the University of California, San Diego, growing insights about a different arm of the immune system, the so-called innate or first response system, have implications for new therapies. One of the first lines of defense against invading bacteria and viruses is a family of proteins called the "toll-like receptors," which are able to distinguish markers or patterns that are unique to these foreign organisms. After recognizing these early signs of infection, the toll receptors signal other immune system players to join the attack to kill and remove the foreign invaders. According to Dr. Krieg, this "infectious-type" recognition pathway appears to also be involved in diseases such as RA and lupus. Dr. Corr reported data suggesting that certain toll receptors appear to help perpetuate the chronic inflammation in RA. There is evidence that antimalarial drugs such as Plaquenil, which can be used to treat RA and lupus, may actually work by blocking this innate response pathway. Dr. Krieg and his colleagues have shown that by creating vaccines that include the unique markers recognized by the toll receptors, you can "trick" the immune system into making a stronger defensive response.</O:P> What's the relevance to people with arthritis? These discoveries show that the "toll road" is not only an exciting new area of research but also that it may be possible to target this arm of the immune system to develop greatly improved therapies that redirect the faulty immune response in RA, lupus and other autoimmune diseases.<O:P> </O:P> Targeting Complement <O:P>
</O:P>The complement system is a series of proteins that "complement" the work of antibodies in destroying foreign invaders. John Atkinson, MD, from Washington University in St. Louis, presented an update on recent progress in understanding of the complement system and how it plays an important role in the inflammation and tissue damage that occurs in diseases like lupus and RA. Interestingly, inherited deficiencies of certain complement proteins are associated with an increased risk of developing lupus. As noted by Craig Gerard, MD, PhD, from Harvard Medical School, several drugs that block the complement pathway are currently in clinical trials in patients with RA and lupus. What's the relevance to people with arthritis? Therapies that block the complement pathway provide a new way to inhibit inflammation and tissue damage in people with RA and lupus. Recent studies supported by the Alliance for Lupus Research and the Arthritis Foundation have found that in a mouse model, such therapies might also prevent pregnancy losses. If this work can be extended to humans, complement proteins would become an important new target for preventing miscarriages in women with lupus and the antiphospholipid syndrome.   
Research Update is compiled by Michele Boutaugh, BSN, MPH, Medical and Scientific Affairs Department, National Office. Source | 
