Research to explore why lupus therapies work for some, not others

Feb 8 2009

The results should shed light not only on the mechanisms behind the disease, but more broadly on the workings of our immune system, especially how our bodies churn out and "train" key combat-ready immune cells, called B-cells.

Such knowledge helps form the basis of treatments not only for lupus but for a swath of autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis.

In autoimmune diseases like lupus, the body fails to properly differentiate between itself and dangerous invaders. Rather than just battling viruses and other harmful foreign materials, B-cells erroneously manufacture "auto-antibodies" directed at the body's and own cells and tissues.

"We're interested specifically in looking at how the bone marrow produces B-cells in the first place, and what quality control checkpoints it imposes to ensure that only healthy cells are released into the bloodstream," Anolik said.

In patients with lupus, the quality control system breaks down, and errant B-cells that are prone to attacking the patient's own body become common. As a result, lupus sufferers can experience inflammation, pain and ultimately, damage to their joints, skin, blood, and even critical organs such as the heart, kidneys and brain. While most people find it to be a controllable disease - perhaps experiencing fatigue, joint pain, or the occasional rash - a smaller set of patients suffer a more extreme disease course, sometimes facing life-threatening problems.

One experimental treatment, pioneered by Anolik and colleagues at Rochester, is known as "B-cell depletion therapy" and significantly reduces the number of B cells in the patient's bloodstream.

"The treatment didn't work across the board, but it was successful for a handful of patients, and in them, the results were striking. This piqued our interest - why does this help some, but not others? We need a clearer picture of what is going on, on a cellular level," said Anolik.

Anolik and her team will also be looking at the effects of interferons, proteins that activate many immune processes. Anolik's team has found that the proteins are overactive in many lupus patients, and scientists are looking at the effects on patients when interferon production is reduced.

"The hope is that this basic research will translate to patients, to understand what exactly goes wrong in each manifestation of the disease, and to help us better tailor therapies that will alleviate each patient's symptoms," Anolik said.

Anolik and her colleagues in the Division of Allergy/Immunology and Rheumatology, rheumatologists Iñaki Sanz, M.D., and R. John Looney, M.D., treat more than 400 lupus patients throughout western New York. Nationally, doctors estimate that anywhere between 500,000 to 1 million Americans have lupus.

Working with Anolik on the study are Jane Liesveld, M.D., professor of Medicine and professor at the James P. Wilmot Cancer Center; Deborah Fowell, Ph.D., associate professor of Microbiology and Immunology; and Frances Lund, Ph.D., professor of Medicine in the Division of Allergy/Immunology and Rheumatology.

The research plays to the Medical Center's historic strength in autoimmune research and therapy. Lupus is also a focus of the Medical Center's Autoimmune Center of Excellence, which is headed by Sanz; it's one of only nine research hubs nationwide funded by the National Institutes of Health to explore the underpinnings of autoimmune diseases.