Memory T cells suggest Parkinson's may be an autoimmune disease

  • Researchers have found a distinct genetic signature in the immune cells of people with Parkinson’s disease.
  • The genes in question are associated with oxidative stress, inflammation, and other immune-related changes.
  • The discovery could lead to new treatments and ways to diagnose Parkinson’s at an early stage before motor symptoms develop.

Parkinson’s disease is a progressive brain disorder that causes shaking, stiffness, walking, balance, and coordination problems.

Almost a million people in the United States have Parkinson’s, and more than 10 million people have the disease worldwide.

Nerve cells produce dopamine, a neurotransmitter or brain hormone that helps to control movement. The death of these cells in a part of the brain called the substantia nigra is responsible for problems with movement, or “motor” symptoms, in Parkinson’s.

However, years before people develop the motor symptoms of Parkinson’s, patients can experience constipation, problems with sleep, and changes in their sense of smell.

Scientists are unsure what the initial trigger for the disease might be, but auto-immunity — when the immune system attacks the body’s own cells — could be one possibility.

“The evidence that [Parkinson’s disease] may partially be an autoimmune disease is just beginning to accumulate,” said James Beck, Ph.D., chief scientific officer of the Parkinson’s Foundation in the United States.

Inflammation is associated with Parkinson’s, and it may be a result of autoimmune processes, he told Medical News Today.

“However, it is not clear what is the trigger that initiates this process,” he said. “That is, inflammation is like a slow burn, but we do not yet know the spark that starts that fire.”

Clumps of a protein called alpha-synuclein, which accumulate inside neurons in the brains of patients, could be the spark that triggers inflammation.

In 2020, scientists at the La Jolla Institute for Immunology in La Jolla, CA, published a study that suggested that the immune system begins to target alpha-synuclein early in the course of Parkinson’s disease.

They found that patients had many immune cells in their blood that responded specifically to alpha-synuclein shortly after their diagnosis.

“Signature” of auto-immunity

The same researchers have now found a distinctive “genetic signature” in memory T cells that respond to alpha-synuclein.

Memory T cells are immune cells that remember the specific molecular features of past infections or autoimmune reactions.

They have published their study in the journal npj Parkinson’s Disease.

“Parkinson’s disease is not usually seen as an autoimmune disease,” says one of the authors, Cecilia Lindestam Arlehamn, Ph.D.

“But all of our work points toward T cells having a role in the disease,” she adds.

However, whether autoimmunity actually causes the disease has yet to be proven.

“At this point, it is not established whether autoimmunity is a prime cause rather than a secondary reaction,” said Alessandro Sette, Dr.Biol.Sci., who co-led the work with Professor Arlehamn.

He told MNT that their earlier research supported the idea that autoimmunity triggers the disease, “but the question is still very open.”

“In any case, even if the T cell reactivity was secondary, it could still have value as a much-needed diagnostic,” he added.

How the study worked

The researchers compared the activity of genes in memory T cells from people with Parkinson’s and those from healthy controls matched for their age.

When they focused on patients whose T cells reacted to alpha-synuclein, they discovered a range of genes with different activity levels than controls.

Among these were genes previously linked to Parkinson’s, including some that are involved in oxidative stress and inflammation.

The genetic signature of Parkinson’s in these cells also included a gene called LRRK2, which is 1 of 2 genes most commonly linked to the “familial” type of Parkinson’s that runs in families.

The gene is known to be active in neurons, where it plays a role in the disease process, but this is the first time scientists have found it to be active in T cells.

“The association of LRRK2 with PD has been known for a long time,” said Professor Sette.

However, the genetic signature includes several other genes not previously linked to the disease.

“What we are most excited about is the large number of new and novel potential targets that the approach has uncovered,” Prof. Sette told MNT.

It may be possible to delay or halt the progression of the disease by targeting these genes in the early stages before motor symptoms develop.

Limitations of the study

The authors report that one of the limitations of their study was that they did not have information about how far the disease had progressed in patients.

In addition, they studied T cells in the bloodstream and did not have direct evidence that these cells actually target neurons in the brains of people with Parkinson’s.

In the future, they plan to study post-mortem brain samples to discover whether this is the case.

Potential treatments and diagnostic tools

The scientists hope that the genetic signature of Parkinson’s in memory T cells could one day help doctors identify people who will develop the disease.

Their discovery could also inspire new treatments that target the proteins that these particular genes make.

“Now that we can see what these T cells are doing, we think intervening with antibody therapies could have an impact on the disease progression, especially early on,” says Prof. Sette.

“A growing number of researchers are becoming interested in the potential of targeting the immune system in the development of treatments that may slow the loss of cells in Parkinson’s — something that no treatment, to date, had been shown to do,” said Professor David Dexter, Ph.D., associate director of research at Parkinson’s U.K.

“This research helps increase our understanding of which targets could provide an opportunity to develop treatments that address the underlying causes of the condition,” he added.

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