CHIT1 at diagnosis predicts faster disability progression and reflects early microglial activation in multiple sclerosis.

Autor: Beliën J; Laboratory for Neuroimmunology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium., Swinnen S; Laboratory for Neuroimmunology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium.; Department of Neurology, University Hospitals Leuven, Leuven, Belgium., D'hondt R; Department of Public Health and Primary Care, KU Leuven, Kortrijk, Belgium.; Imec research group itec, KU Leuven, Kortrijk, Belgium., Verdú de Juan L; Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Vienna, Austria., Dedoncker N; Laboratory for Neuroimmunology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium., Matthys P; Laboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium., Bauer J; Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Vienna, Austria., Vens C; Department of Public Health and Primary Care, KU Leuven, Kortrijk, Belgium.; Imec research group itec, KU Leuven, Kortrijk, Belgium., Moylett S; Laboratory for Neuroimmunology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium., Dubois B; Laboratory for Neuroimmunology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium. benedicte.dubois@uzleuven.be.; Department of Neurology, University Hospitals Leuven, Leuven, Belgium. benedicte.dubois@uzleuven.be.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jun 12; Vol. 15 (1), pp. 5013. Date of Electronic Publication: 2024 Jun 12.
DOI: 10.1038/s41467-024-49312-y
Abstrakt: Multiple sclerosis (MS) is characterized by heterogeneity in disease course and prediction of long-term outcome remains a major challenge. Here, we investigate five myeloid markers - CHIT1, CHI3L1, sTREM2, GPNMB and CCL18 - in the cerebrospinal fluid (CSF) at diagnostic lumbar puncture in a longitudinal cohort of 192 MS patients. Through mixed-effects and machine learning models, we show that CHIT1 is a robust predictor for faster disability progression. Integrative analysis of 11 CSF and 26 central nervous system (CNS) parenchyma single-cell/nucleus RNA sequencing samples reveals CHIT1 to be predominantly expressed by microglia located in active MS lesions and enriched for lipid metabolism pathways. Furthermore, we find CHIT1 expression to accompany the transition from a homeostatic towards a more activated, MS-associated cell state in microglia. Neuropathological evaluation in post-mortem tissue from 12 MS patients confirms CHIT1 production by lipid-laden phagocytes in actively demyelinating lesions, already in early disease stages. Altogether, we provide a rationale for CHIT1 as an early biomarker for faster disability progression in MS.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: