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Stanford Report, March 13, 2002

New antigen microarray technology opens window to better disease screening


Your immune system normally protects against disease, but in some cases — such as with rheumatoid arthritis, lupus, and type-I diabetes — the immune system actually attacks your body. Until now, these disorders, called autoimmune diseases, have been difficult to diagnose and treat.

But a new microarray-based technology developed at the medical center may help solve the problem.

Antigen microarrays, as reported in the March issue of Nature Medicine, give doctors a glimpse of which molecules (antigens) come under attack in an autoimmune disease. By identifying these antigens, doctors can pinpoint diseases and treatment options.

"Right now clinicians test each antigen separately — and each one can take weeks," said P.J. Utz, MD, assistant professor of immunology and rheumatology and senior author on the study. "These arrays could enable a clinician to diagnose the disease on the first visit."

The antigen microarrays — developed in collaboration with Lawrence Steinman, MD, professor of neurology and neurological sciences — consist of glass slides dotted with thousands of proteins and other molecules that are often attacked in autoimmune diseases. To use the microarray, doctors draw a blood sample from the patient and incubate it on the array. Those antibodies that attack molecules on the array will locate their target and latch on. Fluorescent molecules are then added to detect the antibodies, creating colored spots on the slide. From there, it’s a matter of counting the spots to see which antigens the immune system recognized.

In normal people, the antibodies will ignore most antigens on the array. Diabetics, however, may produce arrays with spots corresponding to pancreas cell proteins, and people with rheumatoid arthritis produce spots that correspond to molecules found in the joints.

Utz and William Robinson, MD, PhD, a fellow in the division of immunology and rheumatology and lead author on the paper, eventually hope to uncover the tell-tale patterns of all autoimmune diseases.

Although diagnosing disease may be the microarray’s most immediate use, an array can also help design effective treatment for each patient.

"Prescribing currently available drugs for autoimmune diseases is like taking a sledgehammer to the immune system," Robinson said. Such drugs cripple the immune system, preventing it from attacking the body, but also opening vulnerability to colds and more serious infections.

"One of our primary goals is to use this technology to develop and select antigen-specific therapies to treat autoimmune diseases," he added. Such a treatment could target the immune cells causing tissue damage in an individual patient, rather than hindering the entire immune system. "Antigen-specific therapies will leave the global immune system in place," Robinson said.

Microarrays could also help determine who is at future risk of developing a disease because auto-antibodies may be formed years before signs of illness. "Even if the patients don’t have the disease now, such microarrays may be able to predict which patients are most likely to develop the disease in the next five years," Robinson said. In the future, it may become possible to identify individuals at higher risk — such as those with a family history of autoimmune disease — so they can begin preventive therapy.

Doctors also may use the microarray in clinical trials of a new drug. Utz explained that not all people with a given disease produce the same antibodies. Instead, they may produce two or three out of five that are associated with the disease. By analyzing microarrays of those who respond to a drug and those who don’t, doctors can identify patterns that show who is most likely to benefit from the drug.

New facility lowers costs while expanding access to genomics technology (3/6/02)