The following is a summary of “CHIT1 at diagnosis predicts faster disability progression and reflects early microglial activation in multiple sclerosis,” published in the June 2024 issue of Neurology by Belien, et al.

Due to the highly variable disease course in Multiple sclerosis (MS), accurately predicting a patient’s long-term disability remains a significant hurdle.

Researchers conducted a retrospective study analyzing the cerebrospinal fluid (CSF) of 192 patients with MS at diagnosis, investigating five myeloid markers (CHIT1, CHI3L1, sTREM2, GPNMB, CCL18) to identify potential predictors of disease progression.

They utilized mixed effects and machine learning models to demonstrate CHIT1’s robust prediction of accelerated disability progression (ADP).

The results showed that integrative analysis of 11 CSF and 26 central nervous system (CNS) parenchyma single-cell/nucleus RNA sequencing samples revealed CHIT1 as predominantly expressed by microglia in active MS lesions and enriched for lipid metabolism pathways. Additionally, CHIT1 expression was associated with the shift from a homeostatic to an activated MS-associated cell state in microglia. Neuropathological evaluation in post-mortem tissue from 12 patients with MS confirmed CHIT1 production by lipid-laden phagocytes in actively demyelinating lesions, even in early disease stages.

Investigators identified CHIT1 as a promising early indicator of faster disability progression in patients with MS.

Source: nature.com/articles/s41467-024-49312-y