BACKGROUND: Multiple sclerosis (MS) can be difficult to differentiate from other demyelinating diseases, notably neuromyelitis optica spectrum disorder (NMOSD). We previously showed that NMOSD is distinguished from MS by plasma complement biomarkers. OBJECTIVE: Here, we measure cerebrospinal fluid (CSF) complement proteins in MS, NMOSD and clinically isolated syndrome (CIS), a neurological episode that may presage MS, to test whether these distinguish NMOSD from MS and CIS. MATERIALS AND METHODS: CSF (53 MS, 17 CIS, 11 NMOSD, 35 controls) was obtained; complement proteins (C4, C3, C5, C9, C1, C1q, Factor B (FB)), regulators (Factor I (FI), Factor H (FH), FH-Related Proteins 1, 2 and 5 (FHR125), C1 Inhibitor (C1INH), Properdin) and activation products (terminal complement complex (TCC), iC3b) were quantified by ELISA and results expressed relative to CSF total protein (μg/mg). RESULTS: Compared to control CSF, (1) levels of C4, C1INH and Properdin were elevated in MS; (2) TCC, iC3b, FI and FHR125 were increased in CIS; and (3) all complement biomarkers except TCC, FHR125, Properdin and C5 were higher in NMOSD CSF. A statistical model comprising six analytes (C3, C9, FB, C1q, FI, Properdin) plus age/gender optimally differentiated MS from NMOSD.
BACKGROUND: Multiple sclerosis (MS) can be difficult to differentiate from other demyelinating diseases, notably neuromyelitis optica spectrum disorder (NMOSD). We previously showed that NMOSD is distinguished from MS by plasma complement biomarkers. OBJECTIVE: Here, we measure cerebrospinal fluid (CSF) complement proteins in MS, NMOSD and clinically isolated syndrome (CIS), a neurological episode that may presage MS, to test whether these distinguish NMOSD from MS and CIS. MATERIALS AND METHODS: CSF (53 MS, 17 CIS, 11 NMOSD, 35 controls) was obtained; complement proteins (C4, C3, C5, C9, C1, C1q, Factor B (FB)), regulators (Factor I (FI), Factor H (FH), FH-Related Proteins 1, 2 and 5 (FHR125), C1 Inhibitor (C1INH), Properdin) and activation products (terminal complement complex (TCC), iC3b) were quantified by ELISA and results expressed relative to CSF total protein (μg/mg). RESULTS: Compared to control CSF, (1) levels of C4, C1INH and Properdin were elevated in MS; (2) TCC, iC3b, FI and FHR125 were increased in CIS; and (3) all complement biomarkers except TCC, FHR125, Properdin and C5 were higher in NMOSD CSF. A statistical model comprising six analytes (C3, C9, FB, C1q, FI, Properdin) plus age/gender optimally differentiated MS from NMOSD.
Authors: Eleni Syrimi; Eanna Fennell; Alex Richter; Pavle Vrljicak; Richard Stark; Sascha Ott; Paul G Murray; Eslam Al-Abadi; Ashish Chikermane; Pamela Dawson; Scott Hackett; Deepthi Jyothish; Hari Krishnan Kanthimathinathan; Sean Monaghan; Prasad Nagakumar; Barnaby R Scholefield; Steven Welch; Naeem Khan; Sian Faustini; Kate Davies; Wioleta M Zelek; Pamela Kearns; Graham S Taylor Journal: iScience Date: 2021-10-02
Authors: Alessandro Dinoto; Elia Sechi; Eoin P Flanagan; Sergio Ferrari; Paolo Solla; Sara Mariotto; John J Chen Journal: Front Neurol Date: 2022-03-23 Impact factor: 4.003