Correlations between macrophage/microglial activation marker sTREM-2 and measures of T-cell activation, neuroaxonal damage and disease severity in multiple sclerosis

Zara A Ioannides; Peter A Csurhes; Andrew Swayne; Philippe Foubert; Blake T Aftab; Michael P Pender

doi:10.1177/20552173211019772

Correlations between macrophage/microglial activation marker sTREM-2 and measures of T-cell activation, neuroaxonal damage and disease severity in multiple sclerosis

Mult Scler J Exp Transl Clin. 2021 Jun 3;7(2):20552173211019772. doi: 10.1177/20552173211019772. eCollection 2021 Apr-Jun.

Authors

Zara A Ioannides¹, Peter A Csurhes¹, Andrew Swayne¹, Philippe Foubert, Blake T Aftab², Michael P Pender¹

Affiliations

¹ Faculty of Medicine, The University of Queensland, Brisbane, Australia.
² Preclinical Science and Translational Medicine, Atara Biotherapeutics, South San Francisco, CA, USA.

Abstract

Background: Soluble triggering receptor expressed on myeloid cells-2 (sTREM-2) is a marker of macrophage and microglial activation and is increased in the cerebrospinal fluid (CSF) in multiple sclerosis (MS).

Objective: To determine the relationships among sTREM-2, T cell activation, neuroaxonal damage and clinical features of MS.

Methods: Enzyme-linked immunosorbent assays were used to measure the levels of sTREM-2, soluble CD27 (sCD27, a marker of T cell activation), neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) in the CSF of 42 patients with MS (including nine with clinically isolated syndrome) and 15 patients with other neurological diseases (OND) and in the serum of 164 patients with MS, 87 patients with OND and 62 healthy controls.

Results: sTREM-2 was significantly elevated in the CSF (p = 0.012), but not in the serum, in MS compared to OND. In MS, CSF sTREM-2 correlated positively with CSF sCD27 (p = 0.005), CSF NfL (p = 0.0001), CSF pNfH (p = 0.0006), Expanded Disability Status Scale (EDSS) score (p = 0.0079) and MS Severity Score (MSSS) (p = 0.0006).

Conclusion: In MS the level of sTREM-2 in the CSF is related to measures of T cell activation (sCD27), neuroaxonal damage (NfL and pNfH), disability (EDSS) and disease severity (MSSS).

Keywords: Biomarkers; multiple sclerosis.