Success in Treatment of Children with Juvenile Arthritis

In the May 2, 2005, issue of The Journal of Experimental Medicine, Virginia Pascual, MD, and Jacques Banchereau, Ph D,
from the Baylor Institute for Immunology Research in Dallas (BIIR), report on the successful treatment of children with
systemic onset juvenile idiopathic arthritis (SoJIA). The findings are highly significant for SoJIA patients for whom
previous therapies have failed.


Approximately 250,000 children in the U.S. suffer from juvenile arthritis. SoJIA accounts for about 10 percent of all
juvenile arthritis cases with unknown causes. Early symptoms, which often go undiagnosed, may include fever and a rash. As
the disease progresses, anemia and other blood-related issues develop, as do inflammation and joint pain. Depending on the
duration and severity of the disease long-term disabilities may develop.


"Most of the children in our study have suffered from persistent fever and arthritis for years. Additionally, they have
suffered from side effects resulting from conventional medications. Through this research, we found that we could not only
control the disease, but also allow these children to grow and carry out normal lives," said Dr. Pascual.


In collaboration with researchers from Texas Scottish Rite Hospital for Children in Dallas, the BIIR team identified children
with this form of juvenile arthritis who had not responded to other treatment regimens. They discovered that white blood
cells from these SoJIA patients expressed higher levels of certain immune system genes than white blood cells from healthy
individuals. They also found that blood serum from the SoJIA patients caused healthy white blood cells to start
overexpressing these genes and to secrete higher levels of interleukin-1b. Interleukins are proteins made by white blood
cells that help regulate the immune system. The researchers observed that higher IL-1b secretion also occurred in SoJIA
patients.


"We felt that oversecretion of IL-1b might play a significant role in SoJIA and that inhibiting IL-1b activity could be
beneficial," said Dr. Banchereau, director, BIIR.


To test this hypothesis, nine SoJIA patients received a drug, called Anakinra, which inactivated IL-1. Anakinra, marketed by
Amgen, is a genetically engineered version of the IL-1 receptor that has been used to treat rheumatoid arthritis. All nine
patients responded to the therapy. Seven patients had systemic symptoms, such as fever. A week after the first treatment the
fever was gone from all seven and did not return for the length of the one-year follow up. Eight of the nine had active
arthritis. In these patients, the researchers observed decreases in the arthritic symptoms in the joints as well as
improvement of hemoglobin levels, white blood cell count and a number of other indicators of arthritis. They found that the
therapy completely restored the function of six of the eight patients and lessened the symptoms of the remaining two.



The findings were also presented by Dr. Pascual at the recent Federation of Clinical Immunology Societies Meeting held in
Boston.


Dallas-based Baylor Institute for Immunology Research is the immunology research component of Baylor Research Institute, an
affiliate of Baylor Health Care System. Opened in 1996, Baylor Institute for Immunology Research brings laboratory scientists
and clinicians together in an effort to increase understanding of how the immune system works. The institute is devoted to
translating basic laboratory discoveries made about the immune system into effective treatments for humans. This
interdisciplinary program focuses on developing new therapies, such as dendritic cell therapy, which involves the use of
dendritic cells to modulate the immune response in beneficial ways to treat cancer, infectious diseases, autoimmune diseases,
and transplant rejection.


For more information about Baylor Institute for Immunology Research, visit baylorhealth.