How Antibodies Play a Role in Triggering Neurological Symptoms of Lupus

How Antibodies Play a Role in Triggering Neurological Symptoms of Lupus

How Antibodies Play a Role in Triggering Neurological Symptoms of Lupus













Manhasset, NY (Vocus) November 5, 2010

Many patients with systemic lupus erythematosus (SLE) suffer from a variety of neuropsychiatric problems and scientists at the Feinstein Institute for Medical Research have been trying to understanding the mechanism that underlies these devastating problems. Now, Betty Diamond, MD, head of the Center for Autoimmune and Musculoskeletal Disorders at the Feinstein Institute, has collaborated with colleagues at the Burke Cornell Medical Research Institute to identify two distinct mechanisms that explain the how lupus autoantibodies alter brain function and led to such a wide array of neuropsychiatric complaints.

Patients with lupus, an autoimmune disease that targets many different organs of the body, including the brain, generate autoantibodies that frequently bind double-stranded DNA and cross react with specific glutamate receptors that are toxic to brain cells. The autoantibodies can mediate the cognitive and emotional problems (depression, memory problems and confusion) that are common among lupus patients.

Patricio Huerta, PhD, and Bruce T. Volpe, MD, of the Burke Research Institute have worked with the Diamond lab at the Feinstein to figure out what is going at the level of the neuron that could help explain why the symptoms are so varied. They report in the latest issue of PNAS that the anti-DNA antibody binds to open receptors and that the antibody to the glutamate NMDA receptor only targets activated neurons. At low concentrations, the antibodies augment (NMDA) excitatory post synaptic potentials and at high concentrations they alter mitochondria permeability and cause cell death. This could explain, said Dr. Diamond, why the severity of the symptoms differs from patient to patient.

“This finding helps explain why some cognitive problems are transient and some are permanent,” she said. “Low concentrations of antibody cause transient problems and high concentrations (that lead to cell death) cause life-long problems.”

While this part of the research was conducted in lab dishes, they also studied cerebrospinal fluid samples from lupus patients and found that the levels from low to high concentrations are associated with their symptoms. “We think we understand why some manifestations are transient and some are not,” said Dr. Diamond.

The scientists have worked with medicinal chemists at the Feinstein Institute on the development of drugs that block the antibody from binding to the NMDA receptor. There is now work underway in laboratory models to test whether these can prevent the devastating neuropsychiatric symptoms of lupus.

About The Feinstein Institute for Medical Research

Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research is home to international scientific leaders in cancer, leukemia, lymphoma, Parkinson’s disease, Alzheimer’s disease, psychiatric disorders, substance abuse, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, neuroimmunology, and medicinal chemistry. Feinstein researchers are developing new drugs and drug targets, and producing results where science meets the patient, annually enrolling some 10,000 subjects into clinical research programs.

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8 Replies to “How Antibodies Play a Role in Triggering Neurological Symptoms of Lupus”

  1. cb, I urge you to not drink diet soda if it has aspartame in it. My cousin was diagnosed with lupus at age 40 (she had the lupus wolf rash on her face, the lupus antibodies, everything), was really sick for a year, then someone in the health food industry sent her info that aspartame users can get symptoms of lupus and ms. She quit aspartame that day, threw out all of it, ;and started using stevia to sweeten. Within 2 weeks she was markedly better and 3 months later, the docs told her she didn’t have lupus after all. If you need diet soda, there is one sweetened with stevia called Zevia, and Hansens sweetens their diet soda with splenda, which I think is not as bad.

  2. Reuters – Oil prices tumbled over 4 percent on Wednesday after an unexpected rise in gasoline stocks amid slowing demand sent prices into a tailspin, triggering a five-minute halt in trade and fueling the second big commodities sell-off in a week.

  3. (Federation of American Societies for Experimental Biology) The trip to Mars just got more difficult since researchers discovered that antibodies that fight off disease might become compromised during long-term space flights. A new report published online in the FASEB Journal, shows that antibodies produced in space are less effective than those produced on Earth. This reduced effectiveness of antibodies makes astronauts more susceptible to illness, increasing the danger posed by bacteria and viruses likely to coexist with wayfaring astronauts.

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