New Jefferson Vaccine Successfully Treats Rheumatoid Arthritis
J. Bruce Smith, MD, professor of medicine at Jefferson Medical
College, has developed a new and successful vaccine for treating patients
with rheumatoid arthritis (RA). Results of this research appear in the February
1996 issue of the Journal of Rheumatology.
Dr. Smith and collaborator John Fort, MD, treated 11 female RA patients
with a vaccine made from white blood cells from other individuals. Significant
improvements were noted in 8 of 11 patients by the time of the third injection
with the vaccine, based on noted improvement of joint swelling and pain
and some laboratory tests. No serious side effects were observed.
Female patients with RA undergo symptom remission during pregnancy.
The inspiration for the RA vaccine arose from research into the widely observed
medical phenomena that approximately 70 percent of female RA patients undergo
symptom remission during pregnancy. It is speculated that RA may become
less severe during pregnancy because the mother's immune system manufactures
proteins called cytokines, some of which shield the developing child from
immune attack and rejection. While acting in this manner, the cytokines
may also provide a spin-off benefit by preventing immune attack of the joints
in the mother.
This Jefferson research suggests that a mother's immune reaction against
the foreign proteins on the cells of a fetus plays an important role in
pregnancy-induced remission of RA. "The immune response against fetal
proteins that occurs in a mother during pregnancy is primarily an anti-inflammatory
one so that the fetus doesn't get rejected. We sought to duplicate this
anti-inflammatory effect in nonpregnant RA patients through vaccination
with foreign cells," says Dr. Smith.
David Pitsetsky, MD, medical advisor to the Arthritis Foundation and professor
of medicine at Duke University Medical Center, says "These findings
are very preliminary, but nevertheless suggest that immunization with white
blood cells can influence the pain and swelling of arthritis. It will be
important to determine their mode of action and overall effectiveness."
RA affects more than four-million Americans ­p; approximately 1 in every
10 to 15 adults. It can be a crippling disease that often requires treatment
with drugs that have serious, sometimes dangerous, side effects.
RA is an autoimmune disease that is most likely triggered by an infectious
agent, like a virus. In RA, the immune system continues its attack long
after the agent has left the body. The attack primarily affects the small
joints of the fingers, wrists, neck and jaw through inflammation of the
synovial membranes and joint structures, and by destruction of cartilage
and thinning of the bones. When arthritis develops in a joint, the synovial
membrane becomes thickened and produces large amounts of fluid, causing
pain, swelling, redness and warmth in the affected joint. In late stages
of RA, deformity and immobility may develop.
Participants in the Jefferson study did not become immune to RA. "Cell-based
immunotherapy employed in this study appears to suppress the immune response,
and lead toward RA symptom remission, but the effect is not permanent. Based
on these initial results, we think that repeated treatments will be needed
throughout a patient's life in order to maximize the vaccine's benefits,"
says Dr. Smith.
Trials will determine using technique for both male and female RA patients.
The success of further trials in humans will determine if the same technique
of cell-based immunotherapy may be applied safely in all RA patients ­p;
both male and female. Patients are now being sought for treatment in a placebo-controlled
trial at Jefferson to test efficacy of the vaccine. If these tests are successful,
it is hoped that the vaccine will be widely available within the next two
to three years.
Cell-based immunotherapy also may be applicable to other autoimmune disorders,
such as multiple sclerosis. It also may be applied in the future to graft
rejection after organ transplantation. Dr. Smith, along with F. Susan Cowchock,
MD, also in Jefferson's department of medicine, has used a similar cell-based
immunotherapy for treating nearly 2,000 women who have had unexplained,
recurrent, first-trimester miscarriages.
In the Jefferson RA study, cells contained in the vaccine were obtained
from the blood of donors ­p; in most cases, the patients' spouses. The
results suggest that a better response occurs when the vaccine contains
cells obtained from a spouse rather than a nonspouse. The investigators
postulate that this may be due to repeated exposure to spouse human-leukocyte
antigen (HLA) and/or other antigens through sexual intercourse, though this
is only a theory.
Previous research of female RA patients revealed that when the HLA genes
that a child inherits are dissimilar to its mother's HLA genes, the mother
is more likely to undergo symptom remission during pregnancy. HLA proteins
are intimately involved in stimulating all types of immune responses, such
as graft rejection and protection against viruses and other organisms.