Dr. Betty Diamond: The Lupus Laboratory
Dr. Betty Diamond, one of the country’s leading lupus researcher, has recently moved her laboratory from Columbia Presbyterian to the Feinstein Institute. She studies systemic lupus erythematosus, ab autoimmune disease that can cause any number of symptoms. About 1.5 million people in the United States have lupus, and most are women, with the first hint of symptoms on the brink of adulthood. It is three times more common in Asians, African-Americans and Hispanics than in Caucasians.
Decades ago, many lupus patients died prematurely. Today, the majority of lupus patients survive but it takes a tool in the body and the mind. Many live with damaged organs, blood clots, brain problems and joint inflammation. Kidney damage, common among lupus patients, can be life-threatening. Patients are also at risk for damage to the heart, lung, brain and blood vessels. It is the inflammatory response in the organs that leads to tissue damage.
Several of the new drugs are being studied at the North Shore-Long Island Jewish Health System.
Unraveling how the immune system wages an attack on the body it protects may lead to treatments not only for lupus but for other immune-mediated conditions. The hope is that research could even lead to a prevention or treatment for lupus.
In the human studies under way at the Feinstein Institute, scientists are collecting blood samples from patients and asking them to take a battery of cognitive tests plus a sophisticated brain scan called magnetic resonance spectroscopy, which offers biochemical clues.
The researchers want to figure out whether there is a relationship between the anti-DNA antibodies found in the blood, the symptoms and any abnormalities identified in the scanning.
"We will be able to measure cognitive change over time," said Diamond. "Functional MRI scanning provides an early predictor of cognitive change." The team is also setting up lupus research centers in Queens and at Nassau University Medical Center.
If they can diagnose early and begin treatment, there is less chance that the disease will get out of control, experts say. "One of the problems is the uncertainty of the disease. It flares and remits. Patients don't know what's in store for them," said Furie. "Patients are doing a lot better than they were 50 years ago. But we still have a long way to go."
When the body's immune system senses a threat, it normally goes into action against a real enemy. B-cell lymphocytes respond to foreign invaders by making antibodies. But sometimes, for unknown reasons, the immune system creates antibodies against its own tissue. And that is what happens in lupus.
The B-cell lymphocytes target DNA released from dying cells. These anti-DNA antibodies are known to damage tissue in the kidneys, but researchers at the Feinstein Institute for Medical Research in Manhasset have found there is growing evidence that the brain is affected as well.
Diamond is chief of the institute's Autoimmune Disease Center. She and her colleagues are trying to figure out how and why the anti-DNA antibodies trigger this damage.
In animal models, hormones play a major role, with estrogen at the helm. This could explain why females are nine times more likely to develop lupus than males. In humans, lupus generally emerges after puberty and rarely begins after menopause, when estrogen production diminishes.
Diamond said the hormonal link is hard to pin down in humans. But studies have shown that estrogen does alter the development and function of B-cell lymphocytes. She and her colleagues found that anti-DNA antibodies can leak into the brain through an opening in the blood-brain barrier, which normally keeps antibodies out. Earlier, they showed that anti-DNA antibodies can cross-react with brain cells called NMDA receptors. That means that they fool the brain into thinking they belong at these NMDA receptors, but they don't. And they go on to damage brain tissue.
In animals, symptoms depend on where the antibodies make their entrance. This could explain why some people with lupus have memory problems and others are beset with mental fog and fatigue, Diamond said. Neurological and psychiatric symptoms are common in lupus and can include headache, difficulty expressing thoughts, occasional seizures or strokes.
Infections have been known to temporarily disturb the blood-brain barrier.
Diamond and her colleagues are testing whether the anti-DNA antibodies that cross-react with NMDA receptors play a role in the development of these symptoms. It is thought that patients may have a genetic predisposition to lupus and then an environmental trigger sets the disease in motion.
If Diamond is right that blocking the NDMA reactions could prevent lupus, scientists could find a way to prevent these debilitating brain symptoms.
Because of the findings that implicate NDMA reactions, doctors are testing the benefits of the Alzheimer's drug Namenda, which works directly on NMDA receptors. Animal studies suggest it does protect against the death of the cells that have these receptors.
Researchers are also testing whether stress can weaken the integrity of the blood-brain barrier, as it does in animals. "Stress can worsen lupus," Diamond explained.
