McMaster University

McMaster University

Faculty of
Health Sciences

Research shows abnormal immune system may destroy cells required for normal brain growth and repair

January 6, 2003

McMaster University researcher Boris Sakic has been awarded more than $400,000 Cdn to study mechanisms of brain damage in an autoimmune disease.

The assistant professor of psychiatry and behavioural neurosciences along with four American researchers have been awarded separate grants to study this aspect of an autoimmune disease known as systemic lupus erythematosus. The grants were from the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), of the National Institutes of Health (NIH).

Lupus is a disease which can be fatal, and in which immune cells become confused. Instead of protecting the body by attacking bacteria or virus, they start to attack the body's own cells by producing proteins called autoantibodies. When the brain becomes the target this often results in psychosis, depression and memory loss.

Sakic's recent research indicates that when immune cells get access into the brain, they destroy neurons and, more importantly, the neural stem cells needed for normal brain development and repair by producing toxic autoantibodies. This brain damage may occur in the parts of the brain that control emotions, memory, and hormone release.

These findings are exciting because researchers have believed that autoantibodies may bind to the brain tissue and cause certain forms of schizophrenia, Alzheimer's, epilepsy, and autism. This theory hasn't gained much attention by the scientific community because of inconsistencies and unknown factors that were never fully identified in previous studies.

The present work is a major leap forward, says Sakic, because there is now evidence that an abnormal immune system may interfere with the brain's growth and function.

"While there's still much to be understood, we know a great deal more about the ways immune systems may destroy brain tissue," says Sakic.

"It has long been believed that neurons, the main cells responsible for proper brain function, can't be recovered if lost after birth. But recently it has been discovered otherwise.

"In fetuses, neural stem cells are plentiful. They remain in small numbers until adulthood and are kept, as an emergency supply of sorts, to help replenish cells that might die due to aging or brain disease. We believe that autoantibody-induced destruction of these cells before or after birth might result in underdevelopment of the brain and abnormal brain function.

"For the first time we show that it is possible for these cells to be destroyed by the immune system.

"We hope that by continuing to research this discovery, we can gain a greater understanding of degenerative brain disorders for which medication often does not work," says Sakic. "New treatments based on these findings could mean prevention of mental illness in people who have over-active immune systems."

The research has involved chemically separating parts of the brain fluid from mice to test the role autoantibodies play in the toxicity of the brain fluid. Sakic's team was able to conclude that the death of neural stem cells correlates with toxicity in the brain fluid. The team confirmed the phenomenon in a patient with neuropsychiatric lupus.

Next the team plans to examine exactly where on the surface of a cell these toxic antibodies attach themselves, and how this is relevant to abnormal behaviour.

"The best approach to test cause-and-effect will involve isolating deadly immune cells so we can see more closely how the brain damage of neural stem cells occurs," says Sakic.

Ultimately, the goal of Sakic's research is to improve treatments and ease suffering for people who have diseases such as lupus and different kinds of mental illness.

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