PT  - JOURNAL ARTICLE
AU  - Benjamin J. Murdock
AU  - Diane E. Bender
AU  - Samy R. Kashlan
AU  - Claudia Figueroa-Romero
AU  - Carey Backus
AU  - Brian C. Callaghan
AU  - Stephen A. Goutman
AU  - Eva L. Feldman
TI  - Increased ratio of circulating neutrophils to monocytes in amyotrophic lateral sclerosis
AID  - 10.1212/NXI.0000000000000242
DP  - 2016 Aug 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e242
VI  - 3
IP  - 4
4099  - http://nn.neurology.org/content/3/4/e242.short
4100  - http://nn.neurology.org/content/3/4/e242.full
SO  - Neurol Neuroimmunol Neuroinflamm2016 Aug 01; 3
AB  - 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.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