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

C Bridel; M J A Koel-Simmelink; L Peferoen; C Derada Troletti; S Durieux; R Gorter; E Nutma; P Gami; E Iacobaeus; L Brundin; J Kuhle; H Vrenken; J Killestein; S R Piersma; T V Pham; H E De Vries; S Amor; C R Jimenez; C E Teunissen

doi:https://doi.org/10.1111/nan.12412

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

C Bridel, M J A Koel-Simmelink, L Peferoen, C Derada Troletti, S Durieux, R Gorter, E Nutma, P Gami, E Iacobaeus, L Brundin, J Kuhle, H Vrenken, J Killestein, S R Piersma, T V Pham, H E De Vries, S Amor, C R Jimenez, C E Teunissen

Research output: Contribution to journal › Article › Academic › peer-review

10 Citations (Scopus)

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 three 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 three 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.

Original language	English
Pages (from-to)	404-416
Number of pages	13
Journal	Neuropathology and applied neurobiology
Volume	44
Issue number	4
DOIs	https://doi.org/10.1111/nan.12412
Publication status	Published - Jun 2018

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https://doi.org/10.1111/nan.12412

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Bridel, C., Koel-Simmelink, M. J. A., Peferoen, L., Derada Troletti, C., Durieux, S., Gorter, R., Nutma, E., Gami, P., Iacobaeus, E., Brundin, L., Kuhle, J., Vrenken, H., Killestein, J., Piersma, S. R., Pham, T. V., De Vries, H. E., Amor, S., Jimenez, C. R., & Teunissen, C. E. (2018). Brain endothelial cell expression of SPARCL-1 is specific to chronic multiple sclerosis lesions and is regulated by inflammatory mediators in vitro. Neuropathology and applied neurobiology, 44(4), 404-416. https://doi.org/10.1111/nan.12412

@article{b2f863e964824065be9cb72582527a24,

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

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 three 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 three 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.",

author = "C Bridel and Koel-Simmelink, {M J A} and L Peferoen and {Derada Troletti}, C and S Durieux and R Gorter and E Nutma and P Gami and E Iacobaeus and L Brundin and J Kuhle and H Vrenken and J Killestein and Piersma, {S R} and Pham, {T V} and {De Vries}, {H E} and S Amor and Jimenez, {C R} and Teunissen, {C E}",

year = "2018",

month = jun,

doi = "https://doi.org/10.1111/nan.12412",

language = "English",

volume = "44",

pages = "404--416",

journal = "Neuropathology and applied neurobiology",

issn = "0305-1846",

publisher = "Wiley-Blackwell",

number = "4",

}

Bridel, C, Koel-Simmelink, MJA , Peferoen, L, Derada Troletti, C, Durieux, S, Gorter, R, Nutma, E, Gami, P, Iacobaeus, E, Brundin, L, Kuhle, J, Vrenken, H , Killestein, J , Piersma, SR , Pham, TV , De Vries, HE , Amor, S , Jimenez, CR & Teunissen, CE 2018, 'Brain endothelial cell expression of SPARCL-1 is specific to chronic multiple sclerosis lesions and is regulated by inflammatory mediators in vitro', Neuropathology and applied neurobiology, vol. 44, no. 4, pp. 404-416. https://doi.org/10.1111/nan.12412

TY - JOUR

T1 - Brain endothelial cell expression of SPARCL-1 is specific to chronic multiple sclerosis lesions and is regulated by inflammatory mediators in vitro

AU - Bridel, C

AU - Koel-Simmelink, M J A

AU - Peferoen, L

AU - Derada Troletti, C

AU - Durieux, S

AU - Gorter, R

AU - Nutma, E

AU - Gami, P

AU - Iacobaeus, E

AU - Brundin, L

AU - Kuhle, J

AU - Vrenken, H

AU - Killestein, J

AU - Piersma, S R

AU - Pham, T V

AU - De Vries, H E

AU - Amor, S

AU - Jimenez, C R

AU - Teunissen, C E

PY - 2018/6

Y1 - 2018/6

N2 - 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 three 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 three 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.

AB - 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 three 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 three 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.

U2 - https://doi.org/10.1111/nan.12412

DO - https://doi.org/10.1111/nan.12412

M3 - Article

C2 - 28543098

SN - 0305-1846

VL - 44

SP - 404

EP - 416

JO - Neuropathology and applied neurobiology

JF - Neuropathology and applied neurobiology

IS - 4

ER -