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

TY - JOUR

T1 - Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis

AU - Gjelstrup, Mikkel Carstensen

AU - Stilund, Morten Leif Munding

AU - Petersen, Thor

AU - Møller, Holger Jon

AU - Petersen, Eva Lykke

AU - Christensen, Tove

PY - 2018/2

Y1 - 2018/2

N2 - 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 CD14 and CD16, 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 (CD14+CD16++), with a concomitant significant reduction in classical monocytes (CD14++CD16-) compared with healthy controls. Also, a significant reduction in the surface expression of CD40, CD163, and CD192 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 sCD163 versus CD163, no significant correlations were found, whereas highly significant correlations between levels of soluble neopterine and the intermediate monocyte (CD14++CD16+) 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. Biomarkers for improved diagnostics and prognostics are particularly important in Multiple Sclerosis, due to the heterogeneous disease manifestation and progression of the individual patients. We report increased nonclassical monocyte subsets in peripheral blood from patients with RRMS, PPMS, and CIS, with altered expression of markers of immune activation and inflammation as well as Human Endogenous Retrovirus HERV Env epitopes. These results emphasize the relevance of monocyte subsets, particularly the nonclassical monocytes in monitoring of inflammatory diseases. See also: News and Commentary by Ajami & Steinman.

AB - 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 CD14 and CD16, 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 (CD14+CD16++), with a concomitant significant reduction in classical monocytes (CD14++CD16-) compared with healthy controls. Also, a significant reduction in the surface expression of CD40, CD163, and CD192 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 sCD163 versus CD163, no significant correlations were found, whereas highly significant correlations between levels of soluble neopterine and the intermediate monocyte (CD14++CD16+) 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. Biomarkers for improved diagnostics and prognostics are particularly important in Multiple Sclerosis, due to the heterogeneous disease manifestation and progression of the individual patients. We report increased nonclassical monocyte subsets in peripheral blood from patients with RRMS, PPMS, and CIS, with altered expression of markers of immune activation and inflammation as well as Human Endogenous Retrovirus HERV Env epitopes. These results emphasize the relevance of monocyte subsets, particularly the nonclassical monocytes in monitoring of inflammatory diseases. See also: News and Commentary by Ajami & Steinman.

KW - Biomarkers

KW - ELISA

KW - FLOW Cytometry

KW - HERVs

KW - MS

KW - monocyte subsets

KW - monocytes

KW - multiple sclerosis

UR - http://www.scopus.com/inward/record.url?scp=85042487246&partnerID=8YFLogxK

U2 - 10.1111/imcb.1025

DO - 10.1111/imcb.1025

M3 - Journal article

C2 - 29363161

SN - 0818-9641

VL - 96

SP - 160

EP - 174

JO - Immunology and Cell Biology

JF - Immunology and Cell Biology

IS - 2

ER -