Autoimmunity may have role in Parkinson's disease

For the first time, scientists have found evidence that autoimmunity may have a role in Parkinson's disease. They found that fragments of the protein that builds up in the dopamine cells of the brains of people with Parkinson's trigger an immune response that kills the cells.

The study - led by Columbia University Medical Center in New York City, NY, and the La Jolla Institute for Allergy and Immunology in California - is published in the journal Nature.

The findings raise the possibility that blocking the discovered immune response may offer a new way to slow progression of the brain-wasting disorder.

Parkinson's disease is a movement disorder caused by the loss of dopamine-producing cells in a part of the brain that deals with movement. Dopamine is an important messenger molecule that helps brain cells to communicate with each other.

The main symptoms of Parkinson's disease include tremor, stiffness, slow movement, and impaired balance. These can also be accompanied by depression and emotional changes.

The disease arises more often in people over the age of 60. The symptoms are barely noticeable at first, and progress at different rates in different people. Eventually, it can become very difficult to walk, talk, and live independently.

Worldwide, there are more than 10 million people living with Parkinson's disease, including around a million in the United States. It is 1.5 times more likely to affect men than women.

Alpha-synuclein fragments trigger T cells

There is currently no cure for Parkinson's disease. There are drugs that slow its progression by replenishing depleted dopamine, but these do not suit all patients.

The exact causes of Parkinson's disease are unknown, but an important hallmark is the buildup of damaged alpha-synuclein protein in dopamine-producing cells.

The new study reveals evidence that two fragments of alpha-synuclein can trigger T cells to initiate an attack by the immune system.

The researchers tested blood samples from 67 patients with Parkinson's disease and control samples from 36 healthy patients.

They exposed the blood samples to fragments of proteins found in brain cells, including fragments of alpha-synuclein. The blood from the controls hardly reacted, but T cells in the blood from the Parkinson's patients had a strong reaction to defined fragments from alpha-synuclein.

Link to MHC gene variants

Further investigation revealed that the immune response was linked with variants of a type of gene called the major histocompatibility complex (MHC), which have been found in many people with Parkinson's disease.

MHC genes code for proteins that collect fragments of proteins and "display" them on cell surfaces for T cells to inspect. This is one of the pathways through which the immune system identifies threats.

The finding suggests that certain variants of MHC - such as those associated with Parkinson's disease - may cause T cells to mistakenly identify the alpha-synuclein fragments as pathogens and thus trigger an autoimmune response that destroys the offending cells.

More work will be needed to discover whether the immune response provoked by alpha-synuclein is the primary cause of Parkinson's disease, or whether it merely contributes to brain cell death and disease progression after it is triggered.

"These findings, however, could provide a much-needed diagnostic test for Parkinson's disease, and could help us to identify individuals at risk or in the early stages of the disease."

Study co-leader Prof. Alessandro Sette, Center for Infectious Disease, La Jolla Institute for Allergy and Immunology

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