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

Author

Listed:
  • Jarne Beliën

    (KU Leuven)

  • Stijn Swinnen

    (KU Leuven
    University Hospitals Leuven)

  • Robbe D’hondt

    (KU Leuven
    KU Leuven)

  • Laia Verdú de Juan

    (Medical University of Vienna)

  • Nina Dedoncker

    (KU Leuven)

  • Patrick Matthys

    (KU Leuven)

  • Jan Bauer

    (Medical University of Vienna)

  • Celine Vens

    (KU Leuven
    KU Leuven)

  • Sinéad Moylett

    (KU Leuven)

  • Bénédicte Dubois

    (KU Leuven
    University Hospitals Leuven)

Abstract

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.

Suggested Citation

  • Jarne Beliën & Stijn Swinnen & Robbe D’hondt & Laia Verdú de Juan & Nina Dedoncker & Patrick Matthys & Jan Bauer & Celine Vens & Sinéad Moylett & Bénédicte Dubois, 2024. "CHIT1 at diagnosis predicts faster disability progression and reflects early microglial activation in multiple sclerosis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49312-y
    DOI: 10.1038/s41467-024-49312-y
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