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Multiple sclerosis ( MS ) is an immune mediated, inflammatory and demyelinating disease of the central nervous system ( CNS ). Substantial evidence points toward monocytes and macrophages playing prominent roles early in disease, mediating both pro‐ and anti‐inflammatory responses. Monocytes are subdivided into three subsets depending on the expression of  CD 14 and  CD 16, representing different stages of inflammatory activation. To investigate their involvement in  MS , peripheral blood mononuclear cells from 40 patients with incipient or progressed  MS  and 20 healthy controls were characterized ex vivo. In  MS  samples, we demonstrate a highly significant increase in nonclassical monocytes ( CD 14+ CD 16++), with a concomitant significant reduction in classical monocytes ( CD 14++ CD 16−) compared with healthy controls. Also, a significant reduction in the surface expression of  CD 40,  CD 163, and  CD 192 was found, attributable to the upregulation of the nonclassical monocytes. In addition, significantly increased levels of human endogenous retrovirus ( HERV ) envelope (Env) epitopes, encoded by both  HERV ‐H/F and  HERV ‐W, were specifically found on nonclassical monocytes from patients with  MS ; emphasizing their involvement in  MS  disease. In parallel, serum and cerebrospinal fluid ( CSF ) samples were analyzed for soluble biomarkers of inflammation and neurodegeneration. For  sCD 163 versus  CD 163, no significant correlations were found, whereas highly significant correlations between levels of soluble neopterine and the intermediate monocyte ( CD 14++ CD 16+) population was found, as were correlations between levels of soluble osteopontin and the  HERV  Env expression on nonclassical monocytes. The results from this study emphasize the relevance of further focus on monocyte subsets, particularly the nonclassical monocytes in monitoring of inflammatory diseases.  See also: News and Commentary by  Ajami & Steinman

Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis