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

Mikkel Carstensen Gjelstrup1, Morten Stilund1,2, Thor Petersen2

  • 1Department of Biomedicine, Aarhus University, Bartholin Building, Wilhelm Meyers Allé 4, DK-8000, Aarhus C, Denmark.

Immunology and Cell Biology
|January 25, 2018
PubMed

Insights

Nonclassical monocytes increase in multiple sclerosis (MS), a central nervous system (CNS) disease, correlating with human endogenous retrovirus (HERV) expression. This highlights nonclassical monocytes as key biomarkers for monitoring MS inflammation.

Area of Science:

  • Neuroimmunology
  • Immunology
  • Cellular Biology

Background:

  • Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease of the central nervous system (CNS).
  • Monocytes and macrophages are implicated in MS pathogenesis, exhibiting both pro- and anti-inflammatory functions.
  • Monocytes are classified into subsets (classical, intermediate, nonclassical) based on CD14 and CD16 expression, reflecting inflammatory activation states.

Purpose of the Study:

  • To investigate the role of distinct monocyte subsets in multiple sclerosis (MS).
  • To analyze the expression of specific cell surface markers and human endogenous retrovirus (HERV) epitopes on monocyte subsets in MS patients.
  • To correlate soluble biomarkers in serum and cerebrospinal fluid (CSF) with monocyte populations and HERV expression in MS.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) from 40 MS patients and 20 healthy controls were analyzed ex vivo.
  • Monocyte subsets (classical, intermediate, nonclassical) were identified using CD14 and CD16 surface marker expression.
  • Flow cytometry was used to quantify cell surface markers (CD40, CD163, CD192) and HERV envelope (Env) epitopes on monocyte subsets.
  • Serum and CSF samples were analyzed for soluble biomarkers including sCD163, neopterin, and osteopontin.

Main Results:

  • A significant increase in nonclassical monocytes (CD14+CD16++) and a decrease in classical monocytes (CD14++CD16-) were observed in MS patients compared to controls.
  • Reduced surface expression of CD40, CD163, and CD192 was noted on nonclassical monocytes in MS.
  • Elevated levels of HERV Env epitopes were specifically found on nonclassical monocytes from MS patients.
  • Significant correlations were found between soluble neopterin and intermediate monocytes, and between soluble osteopontin and HERV Env expression on nonclassical monocytes.

Conclusions:

  • Nonclassical monocytes are significantly upregulated in MS and are associated with increased HERV Env expression.
  • The findings underscore the critical role of monocyte subsets, particularly nonclassical monocytes, in MS pathogenesis.
  • Nonclassical monocytes and associated biomarkers may serve as valuable targets for monitoring inflammation in MS.
Keywords:
ELISAMSBiomarkersFLOW CytometryHERVsmonocyte subsetsmonocytesmultiple sclerosis

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