Soluble TREM-2 in cerebrospinal fluid from patients with multiple sclerosis treated with natalizumab or mitoxantrone

Mult Scler. 2016 Oct;22(12):1587-1595. doi: 10.1177/1352458515624558. Epub 2016 Jan 11.


Background: Microglia-mediated proteolysis of the triggering receptor expressed on myeloid cells-2 (TREM-2) produces soluble TREM-2 (sTREM-2) that can be measured in cerebrospinal fluid (CSF) samples. Loss-of-function mutations in TREM2 or in the gene encoding its adaptor protein cause the rare Nasu-Hakola disease (NHD). Multiple sclerosis (MS) is an autoimmune disease that in common with NHD is characterized by demyelination and microglial activation.

Objective: To investigate the potential utility of sTREM-2 as a biomarker for MS and to follow treatment effects.

Methods: sTREM-2 was analyzed in CSF samples from subjects with MS (N = 59); relapsing-remitting MS (RRMS) (N = 36), secondary progressive MS (SPMS) (N = 20) and primary progressive MS (PPMS) (N = 3), and controls (N = 27). CSF levels of sTREM-2 were also assessed before and after treatment of patients with natalizumab or mitoxantrone.

Results: CSF levels of sTREM-2 were significantly increased in patients with RRMS, SPMS, and PPMS compared with controls. After natalizumab treatment, the levels of sTREM-2 were normalized to control levels. The levels of sTREM-2 were also reduced after mitoxantrone treatment.

Conclusion: Increased CSF levels of sTREM-2, a new marker of microglial activation, in MS and normalization upon treatment with either natalizumab or mitoxantrone support a role for microglial activation in active MS.

Keywords: TREM-2; cerebrospinal fluid; immunosuppressive therapy; microglia; mitoxantrone; multiple sclerosis; natalizumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / cerebrospinal fluid
  • Female
  • Follow-Up Studies
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / pharmacology*
  • Male
  • Membrane Glycoproteins / cerebrospinal fluid*
  • Membrane Glycoproteins / drug effects*
  • Middle Aged
  • Mitoxantrone / administration & dosage
  • Mitoxantrone / pharmacology*
  • Multiple Sclerosis, Chronic Progressive / cerebrospinal fluid*
  • Multiple Sclerosis, Chronic Progressive / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / cerebrospinal fluid*
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Natalizumab / administration & dosage
  • Natalizumab / pharmacology*
  • Receptors, Immunologic / drug effects*
  • Topoisomerase II Inhibitors / administration & dosage
  • Topoisomerase II Inhibitors / pharmacology*


  • Biomarkers
  • Immunologic Factors
  • Membrane Glycoproteins
  • Natalizumab
  • Receptors, Immunologic
  • TREM2 protein, human
  • Topoisomerase II Inhibitors
  • Mitoxantrone