YKL-40 is a CSF biomarker of intrathecal inflammation in secondary progressive multiple sclerosis

Burman, Joachim; Raininko, Raili; Blennow, Kaj; Zetterberg, Henrik; Axelsson, Markus; Malmeström, Clas

doi:10.1016/j.jneuroim.2016.01.013

Cited by 71 publications

(60 citation statements)

References 35 publications

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“…; Burman et al . ). Although CHI3L1 correlated with GFAP, only CHI3L1 correlated with clinical measures of progression (i.e., EDSS) and disease severity (i.e., MSSS).…”

Section: Discussionmentioning

confidence: 97%

Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing‐remitting multiple sclerosis

Novakova

Axelsson

Khademi

et al. 2016

Journal of Neurochemistry

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133

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Cerebrospinal fluid (CSF) biomarkers can reflect different aspects of the pathophysiology of relapsing-remitting multiple sclerosis (RRMS). Understanding the impact of different disease modifying therapies on the CSF biomarker profile may increase their implementation in clinical practice and their appropriateness for monitoring treatment efficacy. This study investigated the influence of first-line (interferon beta) and second-line (natalizumab) therapies on seven CSF biomarkers in RRMS and their correlation with clinical and radiological outcomes. We included 59 RRMS patients and 39 healthy controls. The concentrations of C-X-C motif chemokine 13 (CXCL13), C-C motif chemokine ligand 2 (CCL2), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein, neurofilament light protein (NFL), and neurogranin were determined by ELISA, and chitotriosidase (CHIT1) was analyzed by spectrofluorometry. RRMS patients had higher levels of NFL, CXCL13, CHI3L1, and CHIT1 than controls (p < 0.001). Subgroup analysis revealed higher NFL, CXCL13 and CHIT1 levels in patients treated with first-line therapy compared to second-line therapy (p = 0.008, p = 0.001 and p = 0.026, respectively). NFL and CHIT1 levels correlated with relapse status, and NFL and CXCL13 levels correlated with the formation of new magnetic resonance imaging lesions. Furthermore, we found an association between inflammatory and degenerative biomarkers. The results indicate that CSF levels of NFL, CXCL13, CHI3L1, and CHIT1 correlate with the clinical and/or radiological disease activity, providing additional dimensions in the assessment of treatment efficacy.

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“…; Burman et al . ). Although CHI3L1 correlated with GFAP, only CHI3L1 correlated with clinical measures of progression (i.e., EDSS) and disease severity (i.e., MSSS).…”

Section: Discussionmentioning

confidence: 97%

Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing‐remitting multiple sclerosis

Novakova

Axelsson

Khademi

et al. 2016

Journal of Neurochemistry

Self Cite

133

118

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“…Some reports suggest that YKL-40 is additionally a marker of activated astrocytes, 16,19,20 suggesting it indicates pathology of a broader range of cells than neopterin. YKL-40 may be valuable in identifying subclinical cognitive impairment 15 and neurodegenerative processes earlier than symptoms allow.…”

Section: Discussionmentioning

confidence: 99%

Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection

Peluso

Valcour

Phanuphak

et al. 2017

Aids

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Objective To characterize cerebrospinal fluid (CSF) YKL-40, a unique biomarker that reflects activation of microglial cells, in acute (AHI) and chronic HIV-1 infection (CHI) and to determine the effect of treatment initiation on levels of this marker. Design Cross-sectional study of two groups of HIV-infected participants at baseline and follow-up timepoints. Methods AHI (n=33) and CHI (n=34) participants underwent CSF and blood sampling before treatment initiation with combination antiretroviral therapy (cART) and at follow up on cART in a subset of these individuals (6 months in AHI participants [n=24], 1 year in CHI participants [n=10]). Measured parameters were analyzed at each timepoint. Analyses employed Mann-Whitney tests and Spearman correlations. Results Baseline median YKL-40 was higher in CHI than AHI (96844 versus 80754 ng/L; p=0.011). Elevations in the CHI group relative to the AHI group persisted at follow-up despite treatment (87414 versus 66130 ng/L; p=0.003). In untreated CHI, YKL-40 correlated with neopterin (r=0.51, p=0.0025), chemokine (CXC-motif) ligand-10 (r=0.44, p=0.011), and neurofilament light chain (r=0.56, p=0.0008) in CSF. Conclusions This study is the first to describe the dynamics of CSF YKL-40 in two groups of HIV-infected individuals before and after cART and demonstrates the value of this marker in understanding HIV neuropathogenesis. The results suggest the utility of further exploring the prognostic value of YKL-40, particularly in individuals with early HIV infection or those initiating treatment during CHI.

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“…Elevated CSF CHI3L1 levels were found in CIS patients and in patients with optic neuritis (ON) who converted to MS compared to non-conveters (75,95). Increased CHI3L1 levels were found in both RRMS (50, 94, 96, 97) and SPMS (97,98) and have been associated with relapses and number of contrast-enhancing lesions on MRI (50,97,98), but also with disability progression (75,76). Treatment of MS patients (n=19; 17 RRMS, 2 SPMS) with natalizumab during approximately one year significantly reduced CSF CHI3L1 levels (97,99).…”

Section: Chitinase 3-like 1 Proteinmentioning

confidence: 99%

The role of blood and CSF biomarkers in the evaluation of new treatments against multiple sclerosis

Lycke

Zetterberg

2017

Expert Review of Clinical Immunology

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Multiple sclerosis (MS) is an immune-mediated chronic neurodegenerative disease of the central nervous system (CNS). Therapeutic interventions with immunomodulatory agents reduce disease activity and disability development, which are monitored clinically and by magnetic resonance imaging (MRI). However, these measures largely lack information on the impact from these therapies on inflammation, demyelination and axonal injury, the essential pathophysiological features of MS. Several biomarkers for inflammation and neurodegeneration have been detected in cerebrospinal fluid (CSF). In MS, some of these biomarkers seem to reflect disease activity, disability progression, and therapeutic response. Areas covered: In this review, we describe the most promising CSF biomarkers of inflammation and degeneration for monitoring therapeutic interventions in MS. We also describe the evolution of highly sensitive immunoassays that enable determination of neuron-specific biomarkers in blood. Expert commentary: Together with clinical and MRI measures, CSF biomarkers may improve the assessment of therapeutic efficacy and make personalized treatment possible. One disadvantage has been the need of repetitive lumbar punctures to obtain CSF. However, the technical development of highly sensitive immunoassays allows determination of extremely low quantities of neuron-specific proteins in blood. This will potentially open a new era for monitoring disease activity and treatment response in MS.

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YKL-40 is a CSF biomarker of intrathecal inflammation in secondary progressive multiple sclerosis

Cited by 71 publications

References 35 publications

Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing‐remitting multiple sclerosis

Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing‐remitting multiple sclerosis

Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection

The role of blood and CSF biomarkers in the evaluation of new treatments against multiple sclerosis

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