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Soluble TREM-2 in cerebrospinal fluid from patients with multiple sclerosis treated with natalizumab or mitoxantrone
Annika Öhrfelt1, Markus Axelsson2, Clas Malmeström2
1Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden annika.ohrfelt@neuro.gu.se.
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.
Insights
Soluble TREM-2 (sTREM-2) levels in cerebrospinal fluid are elevated in multiple sclerosis (MS) patients. Treatment for MS with natalizumab or mitoxantrone normalizes these sTREM-2 levels, indicating microglial activation in active MS.
Area of Science:
- Neuroimmunology
- Biomarker Discovery
- Neuroinflammation
Background:
- Soluble triggering receptor expressed on myeloid cells-2 (sTREM-2) is produced by microglia and detectable in cerebrospinal fluid (CSF).
- Nasu-Hakola disease (NHD) involves TREM-2 mutations, sharing microglial activation and demyelination features with multiple sclerosis (MS).
Purpose of the Study:
- To evaluate sTREM-2 as a potential biomarker for MS.
- To monitor the impact of MS treatments on sTREM-2 levels.
Main Methods:
- CSF sTREM-2 levels were measured in 59 MS patients (RRMS, SPMS, PPMS) and 27 controls.
- sTREM-2 levels were assessed before and after treatment with natalizumab or mitoxantrone.
Main Results:
- CSF sTREM-2 levels were significantly elevated in all MS subtypes compared to controls.
- Treatment with natalizumab or mitoxantrone led to normalization of sTREM-2 levels.
Conclusions:
- Elevated CSF sTREM-2 in MS patients suggests microglial activation is involved in the disease.
- Normalization of sTREM-2 following treatment supports its role as a marker of active MS and treatment response.
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