An elevated presence of specialized immune cells called alpha-synuclein reactive T-cells were found in patients prior to developing motor symptoms and receiving a diagnosis of Parkinson’s disease, suggesting that increased reactivity of these cells may be present long before clinical diagnosis, according to a recent study published in Nature Communications.
The findings may be used to improve early detection of Parkinson’s disease by indicating increased reactivity of the cells prior to the appearance of motor symptoms and clinical diagnosis, as well as help understand the role of the immune system and inflammation in the pathogenesis of the disease.
“Early detection of Parkinson’s disease, in its prodromal or early clinically symptomatic stages, provides an opportunity to intervene at its earliest stages and potentially affect disease progression or disease symptomatology. These findings may ultimately lead to novel treatments for Parkinson’s disease that modulate the immune system,” said Jennifer Goldman, ’98 MD, MS, professor in the Ken and Ruth Davee Department of Neurology and a co-author of the study.
Parkinson’s disease, a progressive neurodegenerative disease that affects more than ten million people worldwide, presents with both motor and non-motor symptoms in patients. Early stages of the disease are characterized by non-motor symptoms such as constipation, sleep disorders and a reduced ability to smell, and is followed by motor symptoms, when the actual diagnosis is usually made.
Previous studies have shown that T-cells and the immune system play a role in neurodegenerative diseases, including Parkinson’s disease. Specifically, certain T-cell epitopes — specific parts of an antigen to which an antibody binds and leads to an immune system response — related to alpha-synuclein are preferentially recognized in Parkinson’s disease patients, as well as T-cells in regions attacked by the disease.
“This suggests that there may be an autoimmune component to Parkinson’s disease in its development and underlying pathology,” said Goldman, who is also a professor of Physical Medicine and Rehabilitation and Section Chief of Parkinson’s Disease and Movement Disorders at Shirley Ryan AbilityLab.
The investigators examined the reactivity of alpha-synuclein-specific T-cells in two ways: analysis of a case study of a patient who later developed Parkinson’s disease and studying two cohorts of Parkinson’s disease participants alongside a control group without the disease.
In the case study, an individual with Parkinson’s disease presented with strong T-cell reactivity against alpha-synuclein as observed from blood samples taken a decade before their diagnosis. Additionally, the alpha-synuclein reactivity after this individual’s diagnosis was lower than prior levels. This suggested that T-cell reactivity may have potential for early detection of preclinical or premotor Parkinson’s disease and that there may be changes in T-cell reactivity over the span of Parkinson’s from pre-diagnosis to post-diagnosis, according to Goldman.
For the cohorts, alpha-synuclein specific T-cell reactivity was observed in two groups of Parkinson’s disease patients compared to a healthy, age-matched control group. By comparing 11 different epitopes in each participant from each group, the investigators found that T-cell reactivity was higher in those with Parkinson’s disease.
Additionally, T-cell reactivity was associated with early time points in Parkinson’s disease diagnosis: reactivity was higher when closer to Parkinson’s diagnosis and then decreased.
According to Goldman, next steps include replicating the findings in larger population longitudinal studies to detect changes in alpha-synuclein T-cell reactivity over time, additional study of these responses in at-risk populations, and further studying T-cell epitopes and subtypes and their changes over time.
This study was supported by the National Institute of Neurological Disorders and Stroke grants R01NS095435 and P50NS108675, the National Institute of Aging grant P50AG08702, the Parkinson’s Foundation, the Michael J. Fox Foundation, the JPB and William F. Richter Foundations and the La Jolla Institute and University of California, San Diego Program in Immunology.