Study: Immune system may attack memory cells

[Guest guest]

Study: Immune system may attack memory cells

By Talan

Staff Writer

August 20, 2004

In animal research designed to figure out why lupus patients have memory

problems, scientists have discovered that the immune system can send

defensive antibody cells into the brain and selectively kill memory cells.

" This is an important finding that could immediately lead to the development

of treatments to prevent mental impairment in people with auto-immune

disorders, " said Dr. Tracey, head of patient research at North

Shore-Long Island Jewish Research Institute in Manhasset. " The link between

cognition and immunity was unanticipated. "

Not only did the scientists show the immune system antibodies could get into

the brain and target glutamate-rich cells of the hippocampus, the seat of

learning and memory, but they showed the Alzheimer's drug Namenda or

memantine, could block this cell death in animals.

" It brings us a step closer to a rationale for clinical trials in patients, "

said Dr. Betty Diamond, an immunologist and rheumatologist at the Albert

Einstein College of Medicine in the Bronx.

The animal study, in the latest issue of the journal Immunity, was done in

an attempt to understand why so many people with lupus complain of memory

problems. Diamond carried out the study with her husband, Dr. Bruce Volpe, a

neurologist at New York Weill Cornell Medical Center in Manhattan.

Lupus is an auto-immune disorder that affects 500,000 to 1 million people in

the United States, mostly women. The body's immune system turns on itself

and makes specific antibodies that attack the kidneys and other organs. Just

a few decades ago, more than 50 percent of patients died within 10 years

after diagnosis. Today, immunosuppressive drugs are used to keep these

immune cells from damaging tissues, and the majority now live much longer.

However, many patients are now vulnerable to infections because of their

lowered immunity. As patients live longer, memory and learning problems are

becoming more common, Diamond said.

The animal studies allowed them to study how the immune culprits, so-called

anti-DNA antibodies and anti-nuclear antibodies, get into the brain and do

their damage. These antibodies roam the body and for the most part don't

have access to the brain, which is protected by the blood-brain barrier. But

studies have shown that the blood-brain barrier can temporarily open in

response to several things, including infection.

It is only when the blood-brain barrier is breached that the rogue

antibodies get through and head to the hippocampus, where they start killing

the glutamate-containing cells. Somehow, the auto-antibodies cross-react

with these glutamate receptors.

Glutamate is a neurotransmitter that excites cells into action to carry out

a specific job. Too much stimulation of these receptors causes cell death.

The result: The animals suffered the same cognitive, or thinking, problems

as patients do, Diamond said.

But when they gave the animals a dose of the Alzheimer's drug memantine, and

then forced the blood brain barrier open, the glutamate-rich hippocampus

cells did not die. Memantine filled the receptors so the autoantibodies

couldn't get inside the cells to do damage.

Diamond said it is important to conduct clinical trials before lupus

patients add yet another medicine to their treatment mix.

" We have to test whether it works the same way in people, " she said.

Copyright © 2004, Newsday, Inc.