Three important observations emerged from the present study: (i) ALS patients exhibit altered monocyte subset ratios in PB as well as increased levels of activated CD4+ (CSF) and CD8+ T cells (PB and CSF) compared with controls; (ii) decreased intrathecal levels of T-cell regulating CD56bright NK cells are associated with faster disease progression of ALS; and (iii) immunophenotyping may have diagnostic and prognostic value. Here, CD8A is linked to amyotrophic lateral sclerosis.