CSF chitinase 3-like-1 association with disability of primary progressive MS

Pérez‐Miralles, Francisco; Prefasi, Daniel; García‐Merino, Antonio; Gascón-Giménez, Francisco; Medrano, Nicolás; Castillo-Villalba, Jéssica; Cubas, Laura; Alcalá, Carmen; Gil-Perotín, Sara; Gómez-Ballesteros, Rocío; Mauriño, Jorge; Álvarez-García, Esther; Casanova, Bonaventura

doi:10.1212/nxi.0000000000000815

Cited by 30 publications

(25 citation statements)

References 11 publications

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“…Interestingly, we observed that the presence of monocytes/macrophages was associated with conversion to CDMS. This underlines findings on Chitinase 3like 1 (CHI3L1), a glycoprotein secreted by macrophages (41), which was determined as a biomarker in MS (42)(43)(44) and which was also associated with the conversion from CIS to CDMS (45).…”

Section: Discussionsupporting

confidence: 76%

Cerebrospinal Fluid Findings in 541 Patients With Clinically Isolated Syndrome and Multiple Sclerosis: A Monocentric Study

et al. 2021

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BackgroundReports on typical routine cerebrospinal fluid (CSF) findings are outdated owing to novel reference limits (RL) and revised diagnostic criteria of Multiple Sclerosis (MS).ObjectiveTo assess routine CSF parameters in MS patients and the frequency of pathologic findings by applying novel RL.MethodsCSF white blood cells (WBC), CSF total protein (CSF-TP), CSF/serum albumin quotient (Qalb), intrathecal synthesis of immunoglobulins (Ig) A, M and G, oligoclonal IgG bands (OCB) were determined in patients with clinically isolated syndrome (CIS) and MS.ResultsOf 541 patients 54% showed CSF pleocytosis with a WBC count up to 40/μl. CSF cytology revealed lymphocytes, monocytes and neutrophils in 99%, 41% and 9% of patients. CSF-TP and Qalb were increased in 19% and 7% applying age-corrected RL as opposed to 34% and 26% with conventional RL. Quantitative intrathecal IgG, IgA and IgM synthesis were present in 65%, 14% and 21%; OCB in 95% of patients. WBC were higher in relapsing than progressive MS and predicted, together with monocytes, the conversion from CIS to clinically definite MS. Intrathecal IgG fraction was highest in secondary progressive MS.ConclusionsCSF profile in MS varies across disease courses. Blood-CSF-barrier dysfunction and intrathecal IgA/IgM synthesis are less frequent when the novel RL are applied.

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Section: Discussionsupporting

confidence: 76%

Cerebrospinal Fluid Findings in 541 Patients With Clinically Isolated Syndrome and Multiple Sclerosis: A Monocentric Study

et al. 2021

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“…The relevance of CSF CHI3L1 to neurologic disability in PMS was recently reported. 30 In PMS compared with RMS, higher levels of spinal cord atrophy are common findings. 31 …”

Section: Discussionmentioning

confidence: 99%

Chitinase 3–like 1 and neurofilament light chain in CSF and CNS atrophy in MS

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et al. 2021

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo 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.MethodsIn 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.ResultsCHI3L1 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.ConclusionsNfL 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 evidenceThis 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.

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“…In a recent prospective study of 607 patients over 12 years in which serum NfL was measured using Simoa assay, a significant relationship was found between EDSS deterioration and NfL serum levels. However, no association was found between serum NFL levels and long-term disease progression in relapsing and between CSF NFL levels and EDSS scores in primary progressive forms ( 110 , 111 ). These results are contradictory to those found by Barro and Disanto in two different studies, where a correlation was found between high serum NfL levels and long term disability progression in MS ( 112 , 113 ).…”

Section: Biomarkers Associated With Disability Progressionmentioning

confidence: 83%

Deciphering Multiple Sclerosis Progression

et al. 2021

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Multiple sclerosis (MS) is primarily an inflammatory and degenerative disease of the central nervous system, triggered by unknown environmental factors in patients with predisposing genetic risk profiles. The prevention of neurological disability is one of the essential goals to be achieved in a patient with MS. However, the pathogenic mechanisms driving the progressive phase of the disease remain unknown. It was described that the pathophysiological mechanisms associated with disease progression are present from disease onset. In daily practice, there is a lack of clinical, radiological, or biological markers that favor an early detection of the disease's progression. Different definitions of disability progression were used in clinical trials. According to the most descriptive, progression was defined as a minimum increase in the Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 from a baseline level of 0, 1.0–5.0, and 5.5, respectively. Nevertheless, the EDSS is not the most sensitive scale to assess progression, and there is no consensus regarding any specific diagnostic criteria for disability progression. This review document discusses the current pathophysiological concepts associated with MS progression, the different measurement strategies, the biomarkers associated with disability progression, and the available pharmacologic therapeutic approaches.

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CSF chitinase 3-like-1 association with disability of primary progressive MS

Cited by 30 publications

References 11 publications

Cerebrospinal Fluid Findings in 541 Patients With Clinically Isolated Syndrome and Multiple Sclerosis: A Monocentric Study

Cerebrospinal Fluid Findings in 541 Patients With Clinically Isolated Syndrome and Multiple Sclerosis: A Monocentric Study

Chitinase 3–like 1 and neurofilament light chain in CSF and CNS atrophy in MS

Deciphering Multiple Sclerosis Progression

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