Researchers Awarded Grant to Study Genetic Defects in Autoimmune Diseases

CINCINNATI—UC researchers have been awarded a National Institutes of Health (NIH) grant to study defects in the function of the immune system in autoimmunity.

Autoimmunity is the failure of an organism to recognize its own makeup, resulting in an immune response—or fight—against its own cells and tissues.

Laura Conforti, PhD, associate professor in the nephrology and hypertension division, and colleagues within the College of Engineering, received a $429,000 R21 grant that will help fund the two-year interdisciplinary project.

"We will apply nanotechnology to study these defects," she says, noting that the team has primarily been studying ion channels—or proteins—and the role they play in the cause and progression of the autoimmune disease Systemic Lupus Erythematosus (SLE).

SLE affects women in their child-bearing years and is characterized by an overactive immune system that ultimately damages multiple organs, including the kidney, brain and heart.

Conforti says research has shown a defect in the behavior of ion channels that may contribute to the hyperactivity of human T-lymphocytes in patients with SLE.

T-lymphocytes, or T cells, are white blood cells that play a large part in the immune response.

Recent research by Conforti, colleagues in the division and scientists at Cincinnati Children's Hospital Medical Center showed that patients with SLE show protein defects in the immunological synapse.

The immunological synapse is a zone at the point of contact between an antibody-producing—or antigen-presenting cell—and a T cell. This area is where T cells receive their messages to target certain cells and begin destroying them.

"Since many localized events occur at the immunological synapse, it is important to look into the synaptic area and see what events take place there," says Conforti.

With the help of Yeoheung Yun, Mark Schulz and Vesselin Shanov, all with the UC College of Engineering, the team will use unique nanotechnology to produce artificial antigen-presenting cell arrays.

"The arrays consist of polymer surfaces that will allow us to deposit proteins that are expressed on the membrane of antigen-presenting cells in a specific geometry that forces the T cells to form immunological synapses with the array," Conforti explains. "We have created such arrays and are extending this work to incorporate nano-biosensors into these surfaces to measure what happens in the immunological synapse in terms of electrical properties."

This method will allow Conforti and her team to view cell activity at levels unattainable using standard laboratory methods.

Conforti says there are only a few laboratories in the United States conducting these experiments.

"Once we know what happens in normal T cells, we will be able to study how SLE T cells deviate and visualize the abnormalities that underlie the hyperactivity of SLE T cells," she says. 

In addition, Conforti's team is working on a project that will target ion channels for the development of new immunosuppressive treatments.

"Clearly, the interaction among our groups has allowed the development of new approaches to the understanding of the alterations in function of the immune system in autoimmune diseases and the design of novel immunosuppressive therapeutic interventions," she says. "We hope this work will one day provide more efficient patient care."