Objective: To compare the cerebrospinal fluid (CSF) levels of 38 cytokines in multiple system atrophy (MSA) patients vs. control and Parkinson’s disease (PD) subjects.

Background: Neuroinflammation is a potential player in degenerative parkinsonisms, and is suggested to be more relevant in aggressive conditions such as MSA. To date two published studies (using serum and CSF, respectively) have reported increased levels of certain cytokines in MSA. However, these studies assessed a limited number of cytokines, had small samples, and did not compare MSA to PD. Here we chose CSF as a sample more likely to reflect central nervous system processes. We hypothesized that several cytokines are increased in CSF from MSA cases compared to controls and PD patients.

Methods: Cross-sectional multicentre study of a panel of 38 cytokines (HCYTMAG-60K-PX38, MILLIPLEX MAP, Merck Millipore) in CSF from 78 subjects: 40 participants of the Catalan MSA Registry (19 MSAp, 21 MSAc; 31 probable, 9 possible), along with 19 PD patients and 19 neurologically unimpaired controls from the CSF collection of the project leading site.

Results: All groups were comparable in sex distribution (p= 0.61). MSA patients were younger (MSA: 61±8; PD: 66±6; controls: 65±9; p= 0.02). Plate wells with <35 beads and duplicates with a coefficient of variation (CV)>25% were excluded. Of all cytokines, only IL-3 was below the detection range for all the tested samples. As for the other cytokines, up to 12 were assessable in >70 cases, including seven (Flt-3L, GRO, IL8, IP10, MCP-1, MIP-1a, MIP-1b) with data available for all 78 participants. In global and pairwise non-parametric comparisons, the CSF levels of 17 of the 38 cytokines were significantly higher in MSA vs. PD and controls (all p-values <0.05). Five of these were detectable in >70 cases: fractalkine (p=0.002), GRO (p=0.029), IL8 (p=0.023), IL10 (p=0.005) and MDC (p=0.002). Age- and sex-adjusted regression models confirmed these associations.

Conclusions: A number of CSF cytokines appear to be increased in MSA. If confirmed, these findings might have implications in terms of disease knowledge and diagnostic biomarkers. [The authors are grateful to all the participants for their generosity. This study has been funded by Fundació La Marató de TV3 and supported by the CERCA programme of Generalitat de Catalunya.]

References: (1) Kaufman E, Hall S, Surova Y, Widner H, Hansson O, Lindqvist D. Proinflammatory cytokines are elevated in serum of patients with multiple system atrophy. PLoS One 2013; 8: e62354. (2) Yamasaki R, Yamaguchi H, Matsushita T, Fujii T, Hiwatashi A, Kira JI. Early strong intrathecal inflammation in cerebellar type multiple system atrophy by cerebrospinal fluid cytokine/chemokine profiles: a case control study. J Neuroinflammation 2017; 14: 89.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cerebrospinal-fluid-levels-of-cytokines-in-multiple-system-atrophy-a-cross-sectional-study-of-the-atalan-msa-registry-cmsar/