Patient-specific Therapy for Autoimmune 
Diseases Might Soon be a Reality 

Introductory statement

The immune system is designed to protect us against attacks from foreign invaders, but in conditions such as rheumatoid arthritis (RA), lupus, and multiple sclerosis (MS), the immune system mounts an attack on tissues and internal organs. These disorders, called autoimmune diseases, are often difficult to diagnose and treat.  But Arthritis Foundation-funded researchers, Bill Robinson, MD, PhD, and Paul J. Utz, MD, and their colleagues at Stanford University, California, have utilized a new method to identify proteins that stimulate an immune response in autoimmune diseases, and have used this technique to develop specific, targeted therapies. The Stanford research was supported by the National Institutes of Health, the Baxter Foundation, and the Arthritis Foundation.

What problems were studied?
Current therapies for autoimmune diseases primarily act by suppressing the entire immune system, reducing the body’s ability to fight infections and cancer. A therapy that selectively targets the specific proteins that provoke the abnormal immune response would be both more effective and have fewer side effects.  However, the immune system typically attacks many different proteins in autoimmune diseases,  and identifying these specific proteins is a tedious process using traditional testing methods. The Stanford study approached these problems from two angles: first they developed a screening method that could efficiently find the culprit proteins and then they used information obtained from this technique to design a specific vaccine-type therapy.

What was done in the study?
As described in the September 2003 issue of Nature Biotechnology, this particular study focused on the Stanford team’s research with mice with an MS-like disease. (The team is also doing similar experiments with mice that have diseases that resemble lupus and RA.) The investigators utilized a new technology called microarrays, which consist of glass slides dotted with over 2300 proteins and other molecules that could be attacked in autoimmune diseases—in this case, the proteins involved in MS. Then they applied blood taken from the mice with MS to detect antibodies formed against specific proteins. Using fluorescent molecules, the scientists were able to see spots that indicated which proteins were attacked the most often. Using this information, they developed a vaccine that included some of the genetic material (DNA) from these proteins. This “DNA cocktail” functions similarly to allergy shots—which contain the agents causing the allergy so the body can learn to ignore them.  The scientists injected the vaccine into the mice and then used the microarrays to monitor their immune response.

What were the study results?
The Stanford investigators found that the microarrays could be used to identify highly-specific protein “fingerprints” in the mice. Mice with more diverse fingerprints developed more severe disease, leading the investigators to conclude that the microarray analysis could be used to predict disease severity. The team also reported evidence that the autoimmune response was broadly turned off and disease symptoms were significantly reduced in the animals that received the DNA vaccine.

What do these results mean to you?
The most immediate use of the microarray technology may be to speed up the diagnosis of autoimmune diseases. Current testing methods can take weeks, whereas an automated microarray system potentially could return results in a few hours. But as explained by lead author, Bill Robinson, “The greatest potential benefit of this technology is the way in which it can help direct the design of patient-specific treatments.” Such treatments would target just those proteins that cause tissue damage in an individual patient, rather than hindering the entire immune system. This study also suggests that microarrays could be used to predict which patients are more likely to develop more severe disease and to determine who is most likely to benefit from a drug. 

The Arthritis Foundation has funded Dr. Robinson’s laboratory through an Arthritis Investigator Award to perform similar studies using protein arrays and DNA vaccines in mice with a RA-like disease. John H. Klippel, MD, Arthritis Foundation medical director noted, “This research begins to unravel the mysteries of autoimmunity, and offers the potential to revolutionize the way we diagnose, treat, and hopefully cure these diseases.”