PT  - JOURNAL ARTICLE
AU  - Laura Cubas-Núñez
AU  - Sara Gil-Perotín
AU  - Jéssica Castillo-Villalba
AU  - Verónica López
AU  - Luis Solís Tarazona
AU  - Raquel Gasqué-Rubio
AU  - Sara Carratalá-Boscá
AU  - Carmen Alcalá-Vicente
AU  - Francisco Pérez-Miralles
AU  - Hans Lassmann
AU  - Bonaventura Casanova
TI  - Potential Role of CHI3L1+ Astrocytes in Progression in MS
AID  - 10.1212/NXI.0000000000000972
DP  - 2021 May 04
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e972
VI  - 8
IP  - 3
4099  - http://nn.neurology.org/content/8/3/e972.short
4100  - http://nn.neurology.org/content/8/3/e972.full
SO  - Neurol Neuroimmunol Neuroinflamm2021 May 04; 8
AB  - Objective Neurofilament light protein (NfL) and chitinase 3–like 1 (CHI3L1) are biomarkers for acute neuroaxonal damage and local inflammation, respectively. Thus, we set out to evaluate how these biomarkers were associated with clinical features of demyelinating diseases in parallel with the expression in brain autopsies from patients with similar disease stages, assuming their comparability.Methods NfL and CHI3L1 in CSF and serum CHI3L1 were assessed retrospectively in a cross-sectional cohort of controls (n = 17) and patients diagnosed with MS (n = 224), relapsing (n = 163) or progressive (n = 61); neuromyelitis optica (NMO, n = 7); and acute disseminated encephalomyelitis (ADEM, n = 15). Inflammatory activity was evaluated at the time of sampling, and CSF biomarker levels were related to the degree of inflammation in 22 brain autopsy tissues.Results During a clinical attack, the CSF NfL increased in MS, NMO, and ADEM, whereas CHI3L1 was only elevated in patients with NMO and ADEM and in outlier MS patients with extensive radiologic activity. Outside relapses, CHI3L1 levels only remained elevated in patients with progressive MS. CHI3L1 was detected in macrophages and astrocytes, predominantly in areas of active demyelination, and its expression by astrocytes in chronic lesions was independent of lymphocyte infiltrates and associated with active neurodegeneration.Conclusions Both CSF NfL and CHI3L1 augment during acute inflammation in demyelinating diseases. In MS, CHI3L1 may be associated with low-grade nonlymphocytic inflammation and active neurodegeneration and therefore linked to progressive disease.Classification of Evidence This study provides Class III evidence that CSF NfL and CHI3L1 levels increase in inflammatory brain diseases during acute inflammation.ADEM=acute disseminated encephalomyelitis; AMS=acute MS; APP=amyloid precursor protein; BBB=blood-brain barrier; DMT=disease-modifying therapy; EDSS=Expanded Disability Status Scale; GFAP=glial fibrillary acidic protein; IQR=interquartile range; LP=lumbar puncture; NAGM=normal-appearing gray matter; NAWM=normal-appearing white matter; NfL=neurofilament light protein; NMO=neuromyelitis optica; PMS=progressive MS; PPMS=primary progressive MS; SEL=slowly expanding lesion; SPMS=secondary progressive MS; RRMS=relapsing-remitting MS