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.