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Is Parkinson’s an Autoimmune Disease?

T cells see neurons as “foreign invaders,” authors say

The cause of neuronal death in Parkinson’s disease (PD) is still unknown, but a new study proposes that neurons may be mistaken for foreign invaders and killed by the person’s own immune system, similar to the way autoimmune diseases, such as type-1 diabetes, celiac disease, and multiple sclerosis, attack the body’s cells.

The findings were published April 16 in Nature Communications.

“This is a new and likely controversial idea in Parkinson's disease; but if true, it could lead to new ways to prevent neuronal death in Parkinson’s that resemble treatments for autoimmune diseases,” said senior author David Sulzer, PhD, a professor at Columbia University College of Physicians & Surgeons.

For decades, neurobiologists have thought that neurons are protected from attacks from the immune system, partly because they do not display antigens on their cell surfaces. Most cells, if infected by viruses or bacteria, will display bits of the microbe (antigens) on their outer surface. When the immune system recognizes the foreign antigens, T cells attack and kill the cells. Because scientists thought that neurons did not display antigens, they also thought that the neurons were exempt from T-cell attacks.

“That idea made sense because, except in rare circumstances, our brains cannot make new neurons to replenish ones killed by the immune system,” Sulzer said. “But, unexpectedly, we found that some types of neurons can display antigens.”

Cells display antigens with special cell-surface proteins belonging to the major histocompatibility complex (MHC). Using postmortem brain tissue, Sulzer and a colleague, Carolina Cebrián, PhD, noticed that MHC-1 proteins were present in two types of neurons that degenerate during PD.

To determine whether living neurons use MHC-1 to display antigens (and not for some other purpose), Sulzer and Cebrián conducted in vitro experiments with mouse neurons and with human neurons created from embryonic stem cells. These studies showed that under certain circumstances — including conditions known to occur in PD — the neurons use MHC-1 to display antigens. Among the different types of neurons tested, the two types affected in PD were far more responsive than other neurons to signals that triggered antigen display.

The researchers then confirmed that T cells recognized and attacked neurons displaying specific antigens.

The results raise the possibility that PD is partly an autoimmune disease, Sulzer said, but more research is needed to confirm the idea.

If the immune system does kill neurons in PD, Sulzer cautioned that it is not the only thing that goes awry in the disease. “This idea may explain the final step,” he said. “We don’t know if preventing the death of neurons at this point will leave people with sick cells and no change in their symptoms, or not.”

Source: Columbia University Medical Center; April 17, 2014.

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