Abstract
Objective: To elucidate amyotrophic lateral sclerosis (ALS) biomarkers and potential mechanisms of disease, we measured immune cell populations in whole blood from a large cohort of patients with ALS.
Methods: Leukocytes were isolated from the blood of 44 control patients and 90 patients with ALS. The percentages and total numbers of each cell population were analyzed using flow cytometry and matched with patient ALS Functional Rating Scale–Revised (ALSFRS-R) score to correlate leukocyte metrics with disease progression.
Results: We show a significant increase in the percentage of neutrophils and a significant decrease in the percentage of CD4 T cells and CD16− monocytes in the blood of patients with ALS compared to controls; however, only CD16− monocyte levels correlated with disease progression. We also examined the monocyte surface expression of CCRL2 and CCR3; CD16− monocytes displayed decreased percentages and total numbers expressing CCR3, but these numbers did not correlate with ALSFRS-R score. We found that combining multiple disease metrics yielded the most accurate predictor of disease progression: the ratio of neutrophils to CD16− monocytes (N:M ratio) is significantly increased in patients with ALS and better correlates with disease progression than any other single metric.
Conclusions: These observations implicate neutrophils and monocytes as important factors in late disease progression.
GLOSSARY
- ALS=
- amyotrophic lateral sclerosis;
- ALSFRS-R=
- Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised;
- CCR=
- chemokine receptor;
- N:M ratio=
- neutrophil to CD16− monocyte ratio;
- SSC=
- side scatter
Footnotes
↵* These authors contributed equally to this work.
Funding information and disclosures are provided at the end of the article. Go to Neurology.org/nn for full disclosure forms. The Article Processing Charge was paid by the authors.
Supplemental data at Neurology.org/nn
- Received February 1, 2016.
- Accepted in final form March 24, 2016.
- © 2016 American Academy of Neurology
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
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