Researchers have uncovered another piece of the Parkinson’s disease puzzle, identifying that particular immune cells are active long before the hallmark motor symptoms become apparent. It paves the way for the development of earlier diagnostic tools.
Parkinson’s disease (PD) is a complex disease, but with every study we learn more and more about its underlying mechanisms. And, as with many chronic conditions, some research focuses on the “prodromal” stage, when nonspecific symptoms often appear before the more characteristic, diagnosable ones.
A new study led by researchers from the La Jolla Institute for Immunology (LJI) in California has discovered a link between PD and important immune cells called T cells, which appears years before the hallmark motor symptoms do.
“We see these reactive T cells in people after they develop Parkinson’s, but what happens before that?” said Emil Johansson, PhD, the study’s lead author and a visiting scientist who worked in the lab of LJI Professor Alessandro Sette.
T cells are white blood cells that play a crucial role in the body’s immune response, helping to protect against infection and fight pathogens. However, in autoimmune diseases such as type 1 diabetes and rheumatoid arthritis, T cells can either directly harm the body’s own tissues or act as helper cells that enable other immune cells to produce antibodies that attack the body.
PD is characterized by the accumulation of toxic Lewy bodies in the brain, which are primarily composed of the proteins alpha-synuclein and PINK1. LJI researchers had previously found that people with PD have a subtype of T cell that targets these proteins, suggesting the immune system is attacking the brain.
So, for the present study, the researchers asked: Are these T cell responses already present in people who don’t yet have PD, but are at high risk of developing it? They compared three groups of participants. The first was people with PD. The second was “prodromal” individuals who have genetic risk factors or are exhibiting early signs like a reduced sense of smell but don’t yet have a PD diagnosis. The third group was healthy controls.
The researchers found that people at risk of developing PD – the prodromal group – already had elevated T cell responses to alpha-synuclein and PINK1, at levels similar to those with full-blown PD. These responses were significantly higher than in healthy individuals. Male PD patients had higher T cell responses than female PD patients (which aligns with the increased incidence of PD in males); however, in the prodromal group, both men and women showed increased T cell activity. That some women in the prodromal group had elevated immune responses, but might never go on to develop PD, suggests that other protective mechanisms are at play in females.
“Certainly, the fact that this T cell reactivity is highest when patients are closest to a diagnosis is intriguing,” said corresponding author Professor Alessandro Sette, head of the immunology lab at LJI that bears his name. “The finding suggests T cells could have something to do with it.”
But Sette warns that the study’s findings don’t mean that T cells are the only driving force behind the complex disease. They may just be one part of the PD puzzle.
“Parkinson’s disease is associated with the destruction of nervous system cells,” Sette continued. “Does that destruction cause autoimmunity – or is the autoimmunity the cause of the disease? That’s the chicken-and-the-egg of inflammation in Parkinson’s disease.”
Nonetheless, if these immune markers are the body’s “early warning system” for PD, the study’s findings have the potential to guide the development of a diagnostic tool that identifies the disease long before symptoms appear. Further, if the immune system plays an active role in causing damage in early PD, disease progression may be slowed or prevented by calming this immune response. And then there’s the immune response discrepancy between the sexes that requires further investigation.
The study was published in the journal npj Parkinson’s Disease.
Source: LJI
