RT Journal Article
SR Electronic
T1 Chitinase 3–like 1 and neurofilament light chain in CSF and CNS atrophy in MS
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e906
DO 10.1212/NXI.0000000000000906
VO 8
IS 1
A1 Schneider, Ruth
A1 Bellenberg, Barbara
A1 Gisevius, Barbara
A1 Hirschberg, Sarah
A1 Sankowski, Roman
A1 Prinz, Marco
A1 Gold, Ralf
A1 Lukas, Carsten
A1 Haghikia, Aiden
YR 2021
UL http://nn.neurology.org/content/8/1/e906.abstract
AB Objective To investigate cross-sectional associations of CSF levels of neurofilament light chain (NfL) and of the newly emerging marker chitinase 3–like protein 1 (CHI3L1) with brain and spinal cord atrophy, which are established MRI markers of disease activity in MS, to study CHI3L1 and NfL in relapsing (RMS) and progressive MS (PMS), and to assess the expression of CHI3L1 in different cell types.Methods In a single-center study, 131 patients with MS (42 RMS and 89 PMS) were assessed for NfL and CHI3L1 concentrations in CSF, MRI-based spinal cord and brain volumetry, MS subtype, age, disease duration, and disability. We included 42 matched healthy controls receiving MRI. CHI3L1 expression of human brain cell types was examined in 2 published single-cell RNA sequencing data sets.Results CHI3L1 was associated with spinal cord volume (B = −1.07, 95% CI −2.04 to −0.11, p = 0.029) but not with brain volumes. NfL was associated with brain gray matter (B = −7.3, 95% CI −12.0 to −2.7, p = 0.003) but not with spinal cord volume. CHI3L1 was suitable to differentiate between progressive or relapsing MS (p = 0.015, OR 1.0103, CI for OR 1.002–1.0187), and its gene expression was found in MS-associated microglia and macrophages and in astrocytes of MS brains.Conclusions NfL and CHI3L1 in CSF were differentially related to brain and spinal cord atrophy. CSF CHI3L1 was associated with spinal cord volume loss and was less affected than NfL by disease duration and age, whereas CSF NfL was associated with brain gray matter atrophy. CSF NfL and CHI3L1 measurement provides complementary information regarding brain and spinal cord volumes.Classification of evidence This study provides Class II evidence that CSF CHI3L1 is associated with spinal cord volume loss and that CSF NfL is associated with gray matter atrophy.BGM=brain gray matter; BWM=brain white matter; CHI3L1=chitinase 3–like protein 1; CIS=clinically isolated syndrome; DD=disease duration; EDSS=Expanded Disability Severity Scale; HC=healthy control; MUCCA=mean upper cervical cord area; NfL=neurofilament light chain; PMS=progressive MS; RMS=relapsing MS; RRMS=relapsing-remitting MS; scRNA-seq=single-cell RNA sequencing; T1w=T1 weighted