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Stanford Report, May 14, 2003

New approach to genetic screening may rapidly identify immune diseases

By AMY ADAMS

The immune system normally protects the body against foreign invaders, but in diseases such as diabetes, rheumatoid arthritis and multiple sclerosis it turns its attention to the body’s own tissues, destroying the tissue and causing disease.

One goal in treating these disorders is to identify misdirected immune cells when they first appear, then thwart the impending attack. The problem lies in quickly identifying the early signs of disease and in knowing how to redirect the immune system.

Medical center researchers have devised a possible solution to one half of the equation — that of identifying antibodies directed against the body’s tissues, also called autoantibodies. P.J. Utz, MD, assistant professor of medicine, and Hongjie Dai, PhD, associate professor of chemistry, reported in the April 14 issue of Proceedings of the National Academies of Science a novel way of detecting autoantibodies using miniature carbon tubes called nanotubes.

This technology could eventually be used to create arrays of nanotubes that can screen for the presence of as many as 50,000 different autoantibodies on a surface the size of a fingernail.

In previous work, Utz and his colleague William Robinson, MD, PhD, a research associate in the division of immunology and rheumatology, created arrays of proteins, called antigens, from human tissues. If a blood sample contained antibodies to the proteins dotted on glass slides, the antibodies would glom onto the appropriate spot and create a glowing signal, but only after several steps to stain the antibody and scan the results into a computer.

Utz said the new carbon tube technology would perform a similar function, but without the lab work required to stain and scan the array. "What makes this special is that you can look at this in real time," Utz said.

Utz had an interest in antigen arrays when he met Dai, a chemist who works with microscopic carbon straws called nanotubes. These elongated particles change how they conduct electricity when bound to proteins, but when the research collaboration began, the nanotubes bound protein and antibodies indiscriminately.

Dai and his graduate student Robert Chen devised a way to hook antigens from the body to the nanotubes. Now, only antibodies directed against the attached protein could bind the nanotube and change how effectively the tube conducted electricity.

Utz and Dai envision arrays of nanotubes, each bound to a protein from the body. "Each tube would have a different antigen so you could screen hundreds of different antigens at one time," he said. A doctor who suspected autoimmune disease could rinse a patient’s blood serum over the array and simply watch for changes in electrical signals. A change at one spot on the array would indicate an antibody directed against the protein bound to the nanotubes at that location. This is in contrast to current technology that can detect antibodies to only one antigen at a time, and even that requires several days of work.

The group used only nanotubes bound to a single antigen — one that comes under fire in the disease lupus — rather than an entire array. They tested this single protein-nanotube conglomeration with a solution containing an antibody known to bind that protein. With a limited test, the researchers still don’t know how accurate such an array might be. "In the paper we used purified proteins that we knew would interact. That’s very different than working with biological sample like serum," Utz said.

Developing antigen arrays begs the question of whether an autoimmune attack can be halted if researchers do detect antibodies to the body’s tissues. Utz said that some trials in diabetes suggest that the immune system can be redirected during the early stages of the disease. This work is still preliminary and hasn’t been replicated in other autoimmune diseases, Utz said.

Other researchers who participated in the work include postdoctoral fellows Moonsub Shim, PhD, and Katerina Drouvalakis, PhD, and chemistry graduate students Sarunya Bangsaruntip, Nadine Wong Shi Kam, Yiming Li and Woong Kim.




New antigen microarray technology opens window to better disease screening (3/13/02)