Inflammatory profiles relate to survival in subtypes of amyotrophic lateral sclerosis

Mads Nikolaj Olesen, Anna Wuolikainen, Anna Christine Nilsson, Martin Wirenfeldt, Karin Forsberg, Jonna Skov Madsen, Soeren Thue Lillevang, Ivan Brandslund, Peter Munch Andersen, Nasrin Asgari

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OBJECTIVE: To investigate inflammatory cytokines in patients with motor neuron disease (MND) evaluating the putative contribution of amyotrophic lateral sclerosis (ALS)-causing gene variants.

METHODS: This study is a retrospective case series with prospective follow-up (1994-2016) of 248 patients with MND, of whom 164 had ALS who were screened for mutations in the genes for SOD1 and C9orf72. Paired CSF and plasma were collected at the diagnostic evaluation before treatment. A panel of cytokines were measured blindly via digital ELISA on the Simoa platform.

RESULTS: Time from disease onset to death was longer for patients with ALS-causing SOD1 mutations (mSOD1, n = 24) than those with C9orf72 hexanucleotide repeat expansion (C9orf72HRE) ALS (n = 19; q = 0.001) and other ALS (OALS) (n = 119; q = 0.0008). Patients with OALS had higher CSF tumor necrosis factor alpha (TNF-α) compared with those with C9orf72HRE ALS (q = 0.014). Patients with C9orf72HRE ALS had higher CSF interferon alpha compared with those with OALS and mSOD1 ALS (q = 0.042 and q = 0.042). In patients with ALS, the survival was negatively correlated with plasma interleukin (IL) 10 (hazard ratio [HR] 1.17, 95% CI 1.05-1.30). Plasma TNF-α, IL-10, and TNF-related apoptosis-inducing ligand (TRAIL) (HR 1.01 [1.00-1.02], 1.15 [1.02-1.30], and 1.01 [1.00-1.01], respectively) of patients with OALS, plasma IL-1β (HR 5.90 [1.27-27.5]) of patients with C9orf72HRE ALS, and CSF TRAIL (10.5 [1.12-98.6]) of patients with mSOD1 ALS all correlated negatively with survival.

CONCLUSIONS: Differences in survival times in ALS subtypes were correlated with cytokine levels, suggesting specific immune responses related to ALS genetic variants.

TidsskriftNeurology: Neuroimmunology and NeuroInflammation
Udgave nummer3
StatusUdgivet - maj 2020

Bibliografisk note

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.


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