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

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.

• Authors: Annika Öhrfelt, Markus Axelsson, Clas Malmeström, Lenka Novakova, Amanda Heslegrave, Kaj Blennow, Jan Lycke, Henrik Zetterberg
• Journal: Multiple sclerosis (Houndmills, Basingstoke, England) (Mult Scler) Vol. 22 Issue 12 Pg. 1587-1595 (10 2016) ISSN: 1477-0970 [Electronic] England
• PMID: 26754805 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s), 2016.

Chemical References

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

Topics

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