Abstract
ObjectivesChitinase 3-like 1 (CHI3L1) is an extracellular monomeric single-chain glycoprotein expressed by many types of cells. Its elevated levels were found in cerebrospinal fluid in central nervous system (CNS) inflammatory diseases patients. The aim of the study was 1) to validate the reference interval of cerebrospinal fluid (CSF) CHI3L1 in a control group; 2) to measure the CHI3L1 concentration in different diagnosis groups .including multiple sclerosis (MS); and 3) to correlate those values with other biomarkers of axonal damage or neuroinflammation in different grous.MethodsThe study included 132 CSF samples sent to the Department of Clinical Biochemistry, Institute of Laboratory Diagnostics, University Hospital Ostrava. Concentrations of CHI3L1, CXCL13 chemokine, neurofilament light chains, and phosphorylated neurofilament heavy chains were determined by enzyme-linked immunosorbent assays. IgG oligoclonal bands were detected by isoelectric focusing in agarose gels followed by immunofixation. IgM and FLC oligoclonal bands were analyzed by IEF followed by affinity immunoblotting. The group consisted of 42 patients with multiple sclerosis, 14 with clinically isolated syndrome, 11 with other central nervous system inflammatory diseases, 46 with non-inflammatory diseases of the central nervous system, 4 with inflammatory diseases of the peripheral nervous system, and 15 controls.ResultsThe estimated reference values of CHI3L1 were 28.6–182.5 μg.L-1. Statistically significant differences of CSF CHI3L1 concentrations were found among diagnosis groups (p < 0.0001), after age adjustment (p = 0.002). There was a statistically significant relationship between CHI3L1 and NFL in the MS group (rs = 0.460; P = 0.002), and between CHI3L1 and pNFH in the MS group (rs = 0.691; P < 0.001). No statistically significant difference was found in the categorical comparison of CHI3L1 in the MS group and other diagnostic groups as well as when using the Mann-Whitney U test for CHI3L1 with additional parameters with and without oligoclonal bands present.ConclusionsCSF CHI3L1 values differ depending on diagnosis and correlate significantly with concentrations of the axonal damage markers CSF neurofilament light chains, and CSF phosphorylated neurofilament heavy chains, but not with CSF concentrations of the inflammatory marker CXCL13. Thus, CSF CHI3L1 could be another promising prognostic, albeit probably etiologically nonspecific, biomarker of MS.
Highlights
Multiple sclerosis (MS) is a chronic disease affecting the central nervous system
CSF CHI3L1 values differ depending on diagnosis and correlate significantly with concentrations of the axonal damage markers CSF neurofilament light chains, and CSF phosphorylated neurofilament heavy chains, but not with CSF concentrations of the inflammatory marker CXCL13
CHI3L1 is expressed in astrocytes in the brain tissue of patients with multiple sclerosis, and is associated with reactive gliosis in different neuropathological states, those associated with neuroinflammation
Summary
CHI3L1, known as YKL-40, belongs to the chitin glycoside hydrolase 18 family Unlike true chitinases, it lacks enzymatic activity. It is a glycoprotein produced by a wide variety of cells, such as macrophages, chondrocytes, synovial cells, osteoblasts, neutrophils, and astrocytes [4,5,6]. CHI3L1 is expressed in astrocytes in the brain tissue of patients with multiple sclerosis, and is associated with reactive gliosis in different neuropathological states, those associated with neuroinflammation. CHI3L1 is released in vitro from macrophages but the CHI3L1 protein is present in vivo around the microglial nodes in certain astrocytes. CHI3L1 mRNA is expressed by reactive astrocytes surrounding the microglial nodes, suggesting that macrophages release inflammatory mediators that can induce CHI3L1 expression in surrounding astrocytes but not in neurons. The transcription of CHI3L1 by macrophages is likely to be inhibited only after they enter the brain, which may be the cause of the differences observed in other tissue pathologies [8,9]
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