Increased ratio of circulating neutrophils to monocytes in amyotrophic lateral sclerosis.
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.
Department of Neurology (B.J.M., D.E.B., S.R.K., C.F.-R., C.B., B.C.C., S.A.G., E.L.F.) and A. Alfred Taubman Medical Research Institute (E.L.F.), University of Michigan, Ann Arbor.
Benjamin J
BJ
Murdock
Department of Neurology (B.J.M., D.E.B., S.R.K., C.F.-R., C.B., B.C.C., S.A.G., E.L.F.) and A. Alfred Taubman Medical Research Institute (E.L.F.), University of Michigan, Ann Arbor.
Diane E
DE
Bender
Department of Neurology (B.J.M., D.E.B., S.R.K., C.F.-R., C.B., B.C.C., S.A.G., E.L.F.) and A. Alfred Taubman Medical Research Institute (E.L.F.), University of Michigan, Ann Arbor.
Samy R
SR
Kashlan
Department of Neurology (B.J.M., D.E.B., S.R.K., C.F.-R., C.B., B.C.C., S.A.G., E.L.F.) and A. Alfred Taubman Medical Research Institute (E.L.F.), University of Michigan, Ann Arbor.
Claudia
C
Figueroa-Romero
Department of Neurology (B.J.M., D.E.B., S.R.K., C.F.-R., C.B., B.C.C., S.A.G., E.L.F.) and A. Alfred Taubman Medical Research Institute (E.L.F.), University of Michigan, Ann Arbor.
Carey
C
Backus
Department of Neurology (B.J.M., D.E.B., S.R.K., C.F.-R., C.B., B.C.C., S.A.G., E.L.F.) and A. Alfred Taubman Medical Research Institute (E.L.F.), University of Michigan, Ann Arbor.
Brian C
BC
Callaghan
Department of Neurology (B.J.M., D.E.B., S.R.K., C.F.-R., C.B., B.C.C., S.A.G., E.L.F.) and A. Alfred Taubman Medical Research Institute (E.L.F.), University of Michigan, Ann Arbor.
Stephen A
SA
Goutman
Department of Neurology (B.J.M., D.E.B., S.R.K., C.F.-R., C.B., B.C.C., S.A.G., E.L.F.) and A. Alfred Taubman Medical Research Institute (E.L.F.), University of Michigan, Ann Arbor.
Eva L
EL
Feldman