Is Parkinson’s an Autoimmune Disease?

There are roughly 10 million people worldwide living with diagnosed Parkinson’s disease. For these patients and their loved ones, finding answers and effective treatments is extremely important. With so many questions surrounding this enigmatic condition, doctors are now considering whether Parkinson’s might partially be an autoimmune disease.

What Is Parkinson’s Disease?

Parkinson’s is a degenerative neurological disorder that primarily targets the brain cells that produce dopamine. Symptoms change and worsen as the disease progresses, and it is perhaps best known for its hallmark tremors and movement problems.

Common motor symptoms of Parkinson’s include:

  • Tremor (often a rolling sort of hand movement while at rest)
  • Small, slow movements
  • Stiffness in the arms and legs
  • Problems walking and balancing

Common non-motor symptoms include:

  • Anxiety
  • Depression
  • Constipation
  • Poor sense of smell
  • Cognitive difficulties
  • Sleep problems
  • Hallucinations

 

How the Immune System Might Play a Role in Parkinson’s

Parkinson’s disease doesn’t look the same as other known autoimmune diseases. Some features may overlap, but autoimmune diseases are best known for inflammatory symptoms like swollen lymph nodes, joint stiffness, redness, rashes, and pain. Blood tests usually show higher levels of auto-antibodies and immune cells.

The primary outward symptoms of Parkinson’s are quite different, and blood tests don’t typically show higher immune system activity. However, visible symptoms and basic blood test results may not give the full story. Studies from recent years have found other evidence that Parkinson’s may partially be an autoimmune condition.

Immune Activity and Unique Genetics

One link between Parkinson’s and autoimmunity is the way the body reacts to a protein called alpha-synuclein. Patients with Parkinson’s disease experience a buildup of alpha-synuclein in the brain, forming clumps called Lewy bodies. Recent studies found that patients’ blood samples had an increased number of immune cells, which the researchers believe may have been reacting to these Lewy bodies and damaging neurons (nerve cells) in the process.1

Memory T cells are just one type of immune cell that can react to alpha-synuclein, but they’re also a major focus. Interestingly, researchers found a familiar gene active in the T cells of Parkinson’s patients. The gene, known as LRRK2, had already been linked to familial Parkinson’s disease, but had only been known to be active in neurons. Finding it in T cells, then, was an intriguing surprise.2

There’s More Research to Do

We still don’t know exactly what causes Parkinson’s disease or how immune response plays into it. We can’t say for sure that Parkinson’s is an autoimmune disease, but we also can’t rule it out as a factor. Researchers are exploring this area further, but they’re hopeful that the findings may at least help with diagnosis.

Early Autoimmune Signs

Parkinson’s degenerates nerves over time, so catching it early gives doctors and patients the chance to slow the progression and prevent damage. As researchers explore its link to immune response, certain autoimmune symptoms could be helpful early indicators.

Based on research from the La Jolla Institute for Immunology (LIJ), it may be helpful to monitor high-risk patients’ blood for reactive immune cells.3 The study found that alpha-synuclein reactive T cells could be present more than 10 years before a patient is diagnosed with Parkinson’s. If immune response does play a role in development, early detection of this T cell sign could potentially help doctors stop progression earlier or even prevent Parkinson’s altogether.

Autoimmune Reactivity Continues to Change After Diagnosis

If autoimmunity does cause damage in Parkinson’s, it makes sense that lots of reactive T cells would be present around the time of diagnosis. After all, more damage means more symptoms, and more symptoms help lead to a diagnosis. However, this high level of immune cells in the blood doesn’t necessarily stay the same forever.

In a study of patients who were previously diagnosed, researchers found that the number of reactive T cells in the blood declined over time. By roughly 10 years after diagnosis, most patients’ samples had very few reactive T cells. This could mean that if autoimmune damage plays a role, most of the damage happens early on around the time of diagnosis. More research is still needed, but results like these have been eye-openers.

Better Understanding Opens Up New Treatment Possibilities

One of the greatest benefits of medical research is that it opens up new areas of exploration for monitoring and treating patients. With new information about immune function in Parkinson’s disease, doctors may be able to target new bodily systems and processes for treatment.

Future possibilities include (but aren’t limited to):

  • Experimental treatment with immune-suppressing medications
  • Immunotherapy treatments, such as anti-tumor necrosis factor (anti-TNF) therapy
  • New protocols for earlier treatment, focused on reducing inflammation and reactivity

 

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Sources:

  1. https://www.nature.com/articles/s41467-020-15626-w
  2. https://www.nature.com/articles/s41531-022-00282-2
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626019/