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Measurement of soluble CD59 in CSF in demyelinating disease: Evidence for an intrathecal source of soluble CD59

Zelek, Wioleta M., Watkins, Lewis M., Howell, Owain W., Evans, Rhian, Loveless, Samantha, Robertson, Neil P., Beenes, Marijke, Willems, Loek, Brandwijk, Ricardo and Morgan, Bryan Paul 2019. Measurement of soluble CD59 in CSF in demyelinating disease: Evidence for an intrathecal source of soluble CD59. Multiple Sclerosis Journal 25 (4) , pp. 523-531. 10.1177/1352458518758927

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Abstract

Background: CD59, a broadly expressed glycosylphosphatidylinositol-anchored protein, is the principal cell inhibitor of complement membrane attack on cells. In the demyelinating disorders, multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), elevated complement protein levels, including soluble CD59 (sCD59), were reported in cerebrospinal fluid (CSF). Objectives: We compared sCD59 levels in CSF and matched plasma in controls and patients with MS, NMOSD and clinically isolated syndrome (CIS) and investigated the source of CSF sCD59 and whether it was microparticle associated. Methods: sCD59 was quantified using enzyme-linked immunosorbent assay (ELISA; Hycult; HK374-02). Patient and control CSF was subjected to western blotting to characterise anti-CD59-reactive materials. CD59 was localised by immunostaining and in situ hybridisation. Results: CSF sCD59 levels were double those in plasma (CSF, 30.2 ng/mL; plasma, 16.3 ng/mL). Plasma but not CSF sCD59 levels differentiated MS from NMOSD, MS from CIS and NMOSD/CIS from controls. Elimination of microparticles confirmed that CSF sCD59 was not membrane anchored. Conclusion: CSF levels of sCD59 are not a biomarker of demyelinating diseases. High levels of sCD59 in CSF relative to plasma suggest an intrathecal source; CD59 expression in brain parenchyma was low, but expression was strong on choroid plexus (CP) epithelium, immediately adjacent the CSF, suggesting that this is the likely source.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Sage
ISSN: 1352-4585
Date of First Compliant Deposit: 15 March 2018
Date of Acceptance: 18 January 2018
Last Modified: 29 Jun 2019 07:05
URI: http://orca.cf.ac.uk/id/eprint/109894

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