Brain endothelial cell expression of SPARCL-1 is specific to chronic multiple sclerosis lesions and is regulated by inflammatory mediators in vitro.

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Brain endothelial cell expression of SPARCL-1 is specific to chronic multiple sclerosis lesions and is regulated by inflammatory mediators in vitro.

Neuropathol Appl Neurobiol. 2017 May 24;:

Authors: Bridel C, Koel-Simmelink MJA, Peferoen L, Derada Troletti C, Durieux S, Gorter R, Nutma E, Gami P, Iacobeus E, Brundin L, Kuhle J, Vrenken H, Killestein J, Piersma SR, Pham TV, De Vries HE, Amor S, Jimenez CR, Teunissen CE

Abstract
AIMS: Cell matrix modulating protein SPARCL-1 is highly expressed by astrocytes during CNS development and following acute CNS damage. Applying NanoLC-MS/MS to CSF of RRMS and SPMS patients, we identified SPARCL-1 as differentially expressed between these two stages of MS, suggesting a potential as CSF biomarker to differentiate RRMS from SPMS and a role in MS pathogenesis.
METHODS: This study examines the potential of SPARCL-1 as CSF biomarker discriminating RRMS from SPMS in 3 independent cohorts (n=249), analyses its expression pattern in MS lesions (n= 26), and studies its regulation in cultured human brain microvasculature endothelial cells (BEC) after exposure to MS-relevant inflammatory mediators.
RESULTS: SPARCL-1 expression in CSF was significantly higher in SPMS compared to RRMS in a Dutch cohort of 76 patients. This finding was not replicated in 2 additional cohorts of MS patients from Sweden (n=81) and Switzerland (n=92). In chronic MS lesions, but not active lesions or NAWM, a vessel expression pattern of SPARCL-1 was observed in addition to the expression by astrocytes. EC were found to express SPARCL-1 in chronic MS lesions, and SPARCL-1 expression was regulated by MS-relevant inflammatory mediators in cultured human BEC.
CONCLUSIONS: Conflicting results of SPARCL-1's differential expression in CSF of 3 independent cohorts of RRMS and SPMS patients precludes its use as biomarker for disease progression. The expression of SPARCL-1 by BEC in chronic MS lesions together with its regulation by inflammatory mediators in vitro suggest a role for SPARCL-1 in MS neuropathology, possibly at the brain vascular level. This article is protected by copyright. All rights reserved.

PMID: 28543098 [PubMed - as supplied by publisher]

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