New Advances in Pediatric Rheumatology Research

Adapted from the Fall 2013 issue of Discovery to Recovery

Theresa Lu, MD, PhD, associate scientist in the Autoimmunity and Inflammation Program at HSS, is one of only about 200 pediatric rheumatologists in the United States and one of only a handful who conduct research in the laboratory. With support from the NIH and the Lupus Research Institute, Dr. Lu and her team recently made significant progress, moving closer to potential new therapies for children as well as adults with lupus.

Dr. Lu’s research has long focused on lymph node blood vessels that provide nutrients for autoimmune cells, called T cells, that live in lymph nodes. Another type of cell, called a fibroblast, is situated around and near blood vessels. Fibroblasts can dampen the immune activity of T cells.

Recently, Dr. Lu showed that in a model of lupus, a disease in which immune cells become activated in response to their own body, abnormally activated T cells are sequestered in a compartment away from the fibroblasts to which they are usually near. Treatment with a drug called SU5416 disrupted the sequestration and normalized the physical association of T cells with the fibroblasts. Bringing the T cells and fibroblasts back together correlated with dampening of T cell activation and reduced autoantibody generation. The drug seems to have interrupted the abnormal autoimmune response that occurs in lupus.

“We originally used SU5416 to reduce blood vessel growth and starve out the activated immune cells, but the SU5416 had only a temporary effect on the blood vessels. We think the SU5416 had a desirable effect by breaking open the compartments that sequestered the abnormal T cells, allowing the T cells to come into contact with a more immune-dampening environment,” says Dr. Lu. “We are very excited about the idea of a treatment strategy that dampens immune cell activity by altering the microenvironment.”

Further research will determine if SU5416 or drugs in the same class are good treatments for lupus patients and whether better medications can be developed to achieve the same benefits with fewer side effects.

“I always want my laboratory research to be relevant to patient care,” says Dr. Lu. “In the end that’s always the goal – to develop better therapies for patients.”

Read the full Discovery to Recovery Fall 2013 issue.


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