Rheumatoid arthritis may be caused by an antigen that exists
throughout the entire body -- and not just in the joints -- according
to new research conducted in mice.
Scientists led by Dr. Isao Matsumoto, a research fellow at
Harvard Medical School in Boston, studied mice that were
genetically altered to induce a disease similar to rheumatoid
arthritis in humans.
Rheumatoid arthritis is an autoimmune disease wherein the body
attacks its own tissues, mistaking them for a foreign substance.
Membranes of the joints, usually in the hands and feet, become
inflamed, resulting in swelling, pain and often the eventual
destruction of the joint's interior, limiting the joint's range of
motion.
Researchers assumed that rheumatoid arthritis was brought on by
joint-specific antigens -- foreign bodies that were present only in
the joints. However, the researchers found that an antigen -- the
GPI protein -- was present throughout the entire body of mice,
leading the researchers to rethink how rheumatoid arthritis
develops. The cause of the disease is not known.
``The interest of our work is that it tells us that we need to
be open to different mechanisms,'' Matsumoto said. ``Right now, we
can't say that this finding will necessarily benefit humans, but it
has us looking in unexpected places.''
Matsumoto said there seem to be two possibilities as to why the
antigens, which exist throughout the body, affect only the joints.
He explained that either there is something unique about the
protein or something unique about the joints.
First, he said, a modified version of the GPI protein may exist
in the joints but not in the rest of the body, or there may be
unusually high levels of the protein only in the joints. Second,
there may be something about the physiology of the joint that
``traps'' the protein, whereas this does not occur elsewhere.
``We think it's the second theory, though we haven't entirely
ruled out the first,'' said Diane Mathis, a professor of medicine
at Harvard Medical School and one of the study's researchers. She
explained that after injecting mice with certain types of white
blood cells, disease-specific antigens were found throughout the
body. But as antibodies were found fighting the antigens only in
the area of the joints, ``this leads us to believe that it isn't
the antigen but the joints that trigger the autoimmune response,''
she said.
``The antibody is attacking an enzyme in the joints, so there
seems to be something unique about the joint that attracts the
antibody,'' agreed Dr. John Klippel, medical director of the
Arthritis Foundation in Atlanta (www.arthritis.org). ``It has been
hypothesized that there's a foreign antigen or a virus in the joint
causing arthritis, but this study shows that the antigen occurs
throughout the entire body. That is very interesting, but what it
means is anybody's guess.''
The next step, Matsumoto said, is to determine whether the
mechanism of action found in mice is the same in humans with
rheumatoid arthritis.
``We need to find out how the joint specificity comes about,''
Mathis continued. ``That might then provide a clue as to how drugs
might effectively intervene.'' Matsumoto suggested that if further
research can lock down the antibody trigger for attacking the
antigens, vaccination therapies might be a possibility.
