Serum Lymphocyte-Associated Cytokine Concentrations Change More Rapidly over Time in Multiple System Atrophy Compared to Parkinson Disease

Abstract

Objective: Chronic inflammatory processes contribute to the eventual death of motor neurons and the development of symptoms in both idiopathic Parkinson disease (PD) and multiple system atrophy (MSA). Given the faster rate of progression and more severe symptoms associated with MSA, we hypothesized that markers of inflammation would be more evident in the peripheral blood of MSA than PD patients, and that evidence of this inflammation might assist early diagnosis of MSA versus PD. Methods: We performed multiplex analysis to determine the concentrations of 37 immune-associated cytokines and chemokines isolated from the plasma of patients with PD (n = 25) and MSA (n = 14) and compared our results to those of age-matched controls (n = 15). We then applied a mixed-effect multiple regression model to determine if the concentration of cytokines in the plasma of patients with PD and MSA changed significantly over time. Results: Patients with MSA had a trend towards overall lower levels of immune-associated cytokines, while serum cytokine levels were increased in patients with PD. Statistically adjusted comparisons of overall changes in cytokine concentrations between the PD and MSA groups revealed higher concentrations of T-cell-associated cytokines TNFβ and IL-7 in PD. Comparison of samples taken over time revealed significantly faster rates of change in 4 different cytokine concentrations (IL-4, IL-15, IL-2, and IL-9) in patients with MSA versus patients with PD. Conclusions: Our results suggest that single measurements of plasma concentrations of inflammation-associated cytokines cannot be used to distinguish disease states. However, measurements made over time may correlate with pathogenesis. The significant changes in T-cell-associated cytokines may shed light on immune mechanisms that contribute to PD and MSA disease progression.

Allogeneic Bone Marrow–Derived Mesenchymal Stem Cell Safety in Idiopathic Parkinson's Disease

“…8,9 Our group has studied the peripheral immune system in PD neurodegeneration by using LPS rat models, 10,11 glial cells, 12,13 and patient cerebrospinal fluid and blood. 14,15 Results from these investigations indicate that an adaptive immune response contributes to progression and supports the rationale for using an immune-modulatory therapy such as mesenchymal stem cells (MSCs). MSCs have been studied in multiple PD animal models, [16][17][18] and the potential benefit relies primarily on paracrine actions, exosomal activity, and modulation of host immune cells.…”

Patient’s occupation, electric & head trauma in a cohort of 88 multiple system atrophy patients compared with the general population: a hypothesis stimulating pilot study

“…The focus of this study is upon a relatively rare condition, Multiple System Atrophy (MSA) which was once thought to be a variation of Parkinson's Disease and had previously been described as the Shy-Drager syndrome but is now known to be a separate disease entity from Parkinson's. [23][24][25][26][27][28][29][30] . Typically in response to patient need there are self-help generated NGO's and there are now 37 MSA Trust support groups around the UK, reflecting the changing pattern of MSA and the Trust is celebrating its 20 th anniversary.…”

“…23 However, other studies have highlighted changes in the widening understanding of Parkinson type illnesses. [25][26][27][28][29][30] They stated that aside from idiopathic Parkinson syndrome, there are a number of other atypical Parkinsonian syndromes: Dementia with Lewy Bodies (DLB), Progressive Supranuclear Palsy (PSP), Cortico basal Degeneration (CBD) as well as Multiple System Atrophy.However, whilst DLB is relatively a common disease, a prevalence of 0.4% (400 cases per 100,000 persons) the later studies found that MSA and PSP have a prevalence of between 5 to 10 per 100,000 persons respectively, [23][24][25][26]29,30 virtually doubling the estimates of MSA a decade earlier 23 which mirrors the growing number of MSA Trustsupport groups across the UK.…”

“…From the first paper in 1977 it took until 1987 to have 100papers but between January 2017 and January 2018 there were 145 specific MSA studies, strongly indicating rises in MSA morbidity and from countries around the world not just amongst Western countries. 3,11,[24][25][26][27][28][29][30][31] Inevitably there has been speculation as to the presumed multiple environmental and epigenetic aetiology of MSA. Whilst some studies have found little statistical association between occupations, especially pesticides and solvents with neurological disease, 31,32 others have found a range of possible environmental influences, including solvents, pesticides, heavy metals and air pollution 31-36.…”

TNFα inhibitors as targets for protective therapies in MSA: a viewpoint

“…High expression of TNFα in degenerating regions suggests that this potent pro-inflammatory cytokine is a mediator of neuronal injury. Furthermore, markers of inflammation such as serum T-lymphocyte-associated cytokine concentrations give evidence of immune mechanisms contributing to PD and MSA disease progression [73]. The pathobiological effects of TNFα in neurodegeneration and, in particular, in PD have been critically reviewed recently [17].…”