03-22-2002
Autoimmune disorders like rheumatoid arthritis, lupus, and type I diabetes are difficult conditions to diagnose and treat. But a new microarray-based technology developed at Stanford University Medical Center may address this chronic problem.
Antigen microarrays give doctors a glimpse at which molecules (antigens) come under attack in an autoimmune disease. By identifying these antigens, doctors can pinpoint diseases and develop treatment options. This is according to the March issue of Nature Medicine.
"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 consist of glass slides dotted with thousands of proteins and other molecules that are often attacked in autoimmune disease. 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 to them. 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. However in rheumatoid arthritis patients, for example, they may produce arrays with spots that correspond to molecules found in the joints, and diabetics may produce spots corresponding to pancreas cell proteins.
Utz and William Robinson, MD, PhD, from 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 treatments for each patient.
"One of our primary goals is to use this technology to develop and select antigen-specific therapies to treat autoimmune diseases," Robinson said. Such a treatment could target the immune cells causing tissue damage in an individual patient, rather than hindering the entire immune system. Current medications often cripple the immune system, preventing it from attacking the body, but also opening vulnerability to colds and more serious infections. "Antigen-specific therapies will leave the global immune system in place," Robinson added.
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.