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Immunology 101: Pathways to a Cure
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
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.
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.
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.
Taking the “Toll Road”: Your Frontline Defense
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.
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.
Targeting Complement
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.
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