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

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

Author information

1
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden annika.ohrfelt@neuro.gu.se.
2
Department of Neurology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
3
UCL Institute of Neurology, University College London (UCL), London, UK.
4
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
5
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden/UCL Institute of Neurology, University College London (UCL), London, UK.

Abstract

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

PMID:
26754805
DOI:
10.1177/1352458515624558
[Indexed for MEDLINE]

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