NEW YORK, May 31 (Reuters Health) - Mice with a rheumatoid arthritis-like
disease are less likely to have joint swelling or joint destruction if given
injections of a specific type of antibody, researchers report.
The treatment could "provide a new and unexpected option" for treating
rheumatoid arthritis, according to investigators from the Imperial College
School of Medicine in London, UK, led by Dr. Marco Londei. Rheumatoid arthritis,
an autoimmune disease in which the body's defenses attack its own tissues, is
more common in women, tends to strike between the ages of 36 and 50, and results
in a chronic destruction and deformity of the joints.
However, the authors note that there is one problem with their finding. The
antibody, which binds to the CD40 molecule on the surface of certain immune
system cells, has been found in past studies to boost--rather than suppress--the
immune system. It would seem that boosting the immune system could be dangerous
in patients struggling with an overzealous and abnormal immune reaction.
In a commentary accompanying the report in the June issue of Nature
Medicine, Drs. Rene Toes and E. Zanelli of the Leiden University Medical Center
in the Netherlands, write that "these observations and speculations are very
relevant to human rheumatoid arthritis." However, for human patients with
autoimmune diseases, the potential risks associated with an antibody that binds
to CD40 "are, at present, unacceptably high," they note.
"Eventually, this knowledge could be used for the development of new
therapeutic strategies to fight immune attack of otherwise healthy tissues,"
conclude the Dutch scientists.
In the immune system, two molecules found on immune system cells--CD40 and
CD154--interact and play a key role in regulating immune responses. Antibodies
that bind to CD40 can mimic the action of CD154, essentially cranking up the
immune response and proving useful in combating diseases such as cancer.
Conversely, interrupting their interaction has been found to dampen the immune
reaction, preventing rejection of transplanted kidneys in animal studies.
In the new study, Londei and colleagues used two different types of
CD40-stimulating antibodies to treat mice with a rheumatoid arthritis-like
illness, which is induced by injections of a type of collagen.
While 61% of the joints of the mice normally develop severe damage,
including destruction of bone, only 17% of the joints of mice treated with an
antibody were severely damaged. Overall, the treated mice tended to have only
mild inflammation, little erosion of cartilage and few signs of inflammation,
the researchers report.
Because of the previous research showing that CD40 antibodies can boost the
body's immune response, the investigators looked to see if the timing of the
antibody treatment made a difference. They found that when it was administered
before the collagen injections, neither antibody prevented arthritis in the
mice.
"In our experimental model, the timing of the administration of monoclonal
antibodies against CD40 seems essential for the outcome," Londei and colleagues
conclude.
More research is needed to determine if the antibodies are safe or effective
in humans.
