KU Leuven
Neurosciences

Author Of 1 Presentation

Biomarkers and Bioinformatics Poster Presentation

P0038 - CHIT1 at Diagnosis Reflects Long-Term Multiple Sclerosis Disease Activity (ID 783)

Speakers
Presentation Number
P0038
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Evidence for a role of innate immune cells such as the CNS-resident macrophages or microglia in MS pathogenesis is growing, and the heterogeneity of microglial subsets is increasingly recognized. Several biomarkers directly reflect the neurodegenerative and inflammatory processes in MS. Macrophage and microglia-related biomarkers in CSF have been reported in other neurological diseases.

Objectives

We investigated association of microglial markers at time of diagnostic lumbar puncture (LP) with different aspects of disease activity
(relapses, disability, magnetic resonance imaging parameters) up to 6 years later in a cohort of 143 patients.

Methods

In cerebrospinal fluid (CSF), we measured 3 macrophage and microglia-related proteins, chitotriosidase (CHIT1), chitinase-3–like protein 1 (CHI3L1 or YKL-40), and soluble triggering receptor expressed on myeloid cells 2 (sTREM2), as well as a marker of neuronal damage, neurofilament light chain (NfL), using enzyme-linked immunosorbent assay and electrochemiluminescence. We investigated the same microglia-related markers in publicly available RNA expression data from postmortem brain tissue.

Results

CHIT1 levels at diagnostic LP correlated with 2 aspects of long-term disease activity after correction for multiple testing. First, CHIT1 increased with reduced tissue integrity in lesions at a median 3 years later (p = 9.6E-04). Second, CHIT1 reflected disease severity at a median 5 years later (p = 1.2E-04). Together with known clinical covariates, CHIT1 levels explained 12% and 27% of variance in these 2 measures, respectively, and were able to distinguish slow and fast disability progression (area under the curve = 85%). CHIT1 was the best discriminator of chronic active versus chronic inactive lesions and the only marker correlated with NfL (r = 0.3, p = 0.0019). Associations with disease activity were, however, independent of NfL.

Conclusions

CHIT1 CSF levels measured during the diagnostic LP reflect microglial activation early on in MS and can be considered a valuable prognostic biomarker for future disease activity.

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