RT Journal Article
SR Electronic
T1 Increased ratio of circulating neutrophils to monocytes in amyotrophic lateral sclerosis
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e242
DO 10.1212/NXI.0000000000000242
VO 3
IS 4
A1 Benjamin J. Murdock
A1 Diane E. Bender
A1 Samy R. Kashlan
A1 Claudia Figueroa-Romero
A1 Carey Backus
A1 Brian C. Callaghan
A1 Stephen A. Goutman
A1 Eva L. Feldman
YR 2016
UL http://nn.neurology.org/content/3/4/e242.abstract
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