RT Journal Article
SR Electronic
T1 Potential Role of CHI3L1+ Astrocytes in Progression in MS
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e972
DO 10.1212/NXI.0000000000000972
VO 8
IS 3
A1 Laura Cubas-Núñez
A1 Sara Gil-Perotín
A1 Jéssica Castillo-Villalba
A1 Verónica López
A1 Luis Solís Tarazona
A1 Raquel Gasqué-Rubio
A1 Sara Carratalá-Boscá
A1 Carmen Alcalá-Vicente
A1 Francisco Pérez-Miralles
A1 Hans Lassmann
A1 Bonaventura Casanova
YR 2021
UL http://nn.neurology.org/content/8/3/e972.abstract
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