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Inflammatory markers in cerebrospinal fluid: independent prognostic biomarkers in amyotrophic lateral sclerosis?
  1. Benjamin Gille1,2,
  2. Maxim De Schaepdryver1,3,
  3. Lieselot Dedeene1,3,
  4. Janne Goossens1,
  5. Kristl G Claeys4,5,
  6. Ludo Van Den Bosch6,7,
  7. Jos Tournoy2,8,
  8. Philip Van Damme4,7,
  9. Koen Poesen1,3
  1. 1 Department of Neurosciences, Laboratory for Molecular Neurobiomarker Research, KU Leuven, Leuven, Belgium
  2. 2 Department of Chronic Disease, Metabolism and Ageing, KU Leuven, Leuven, Belgium
  3. 3 Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
  4. 4 Department of Neurology, Neuromuscular Reference Centre, University Hospitals Leuven, Leuven, Belgium
  5. 5 Department of Neurosciences, Laboratory for Muscle Diseases and Neuropathies, KU Leuven, Leuven, Belgium
  6. 6 Department of Neurosciences, Laboratory of Neurobiology, KU Leuven, Leuven, Belgium
  7. 7 VIB, Center for Brain & Disease Research, KU Leuven, Leuven, Belgium
  8. 8 Department of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium
  1. Correspondence to Professor Koen Poesen, Department of Neurosciences, Laboratory for Molecular Neurobiomarker Research, KU Leuven, Leuven B-3000, Belgium; koen.poesen{at}uzleuven.be

Abstract

Objective Inflammation is a key pathological hallmark in amyotrophic lateral sclerosis (ALS), which seems to be linked to the disease progression. It is not clear what the added diagnostic and prognostic value are of inflammatory markers in the cerebrospinal fluid (CSF) of patients with ALS.

Methods Chitotriosidase-1 (CHIT1), chitinase-3-like protein 1 (YKL-40) and monocyte chemoattractant protein-1 (MCP-1) were measured in CSF and serum of patients with ALS (n=105), disease controls (n=102) and patients with a disease mimicking ALS (n=16). The discriminatory performance was evaluated by means of a receiver operating characteristic curve analysis. CSF and serum levels were correlated with several clinical parameters. A multivariate Cox regression analysis, including eight other established prognostic markers, was used to evaluate survival in ALS.

Results In CSF, CHIT1, YKL-40 and MCP-1 showed a weak discriminatory performance between ALS and ALS mimics (area under the curve: 0.79, p<0.0001; 0.72, p=0.001; 0.75, p=0.001, respectively). CHIT1 and YKL-40 correlated with the disease progression rate (ρ=0.28, p=0.009; ρ=0.34, p=0.002, respectively). CHIT1 levels were elevated in patients with a higher number of regions displaying motor neuron degeneration (one vs three regions: 4248 vs 13 518 pg/mL, p = 0.0075). In CSF, YKL-40 and MCP-1 were independently associated with survival (HR: 29.7, p=0.0003; 6.14, p=0.001, respectively).

Conclusions Our findings show that inflammation in patients with ALS reflects the disease progression as an independent predictor of survival. Our data encourage the use of inflammatory markers in patient stratification and as surrogate markers of therapy response in clinical trials.

  • amyotrophic lateral sclerosis
  • inflammation
  • biomarker
  • survival
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Footnotes

  • BG and MDS are shared first authorship.

  • PVD and KP are shared last authorship.

  • Contributors Concept and design: BG, MDS, PVD, KP and JT. Drafting of the manuscript and figures: BG, MDS, KP and LD. Acquisition, analysis or interpretation of data: BG, MDS, LD, JG, KC, LVDB, JT, PVD and KP. Critical revision of the manuscript for important intellectual content: all authors.

  • Funding The work was supported by the agency Flanders Innovation & Entrepreneurship, Opening the Future Fund (KU Leuven), the Interuniversity Attraction Poles programme P7/16 of the Belgian Federal Science Policy Office, the Flemish Government initiated Flanders Impulse Programme on Networks for Dementia Research, the European Union Joint Programme-Neurodegenerative Disease Research project STRENGTH and RiMod-FTD, the European E-Rare-2 project PYRAMID. MDS has a PhD Fellowship of the Research Foundation—Flanders (11E6319N) and a grant of the Rotary’s ‘Espoir en Tête—Hoofd zaak er is Hoop’. LD is funded by a PhD Fellowship of the Research Foundation—Flanders (FWO-Vlaanderen) (1165119N). PVD holds a senior clinical investigatorship of FWO-Vlaanderen and is supported by the ALS Liga Belgium and the KU Leuven ALS fund ‘Een hart voor ALS’ and ‘Laeversfonds voor ALS onderzoek’.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Ethics approval The study was approved by the Ethical Committee of the University Hospitals of Leuven.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.

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