Multiplex assessment of cerebrospinal fluid biomarkers in multiple sclerosis.

BACKGROUND

Several roles for biomarkers in multiple sclerosis (MS) exist, including aiding in the diagnosis of MS, predicting disease activity or progression, and defining individuals who may be responsive to specific treatments. Cerebrospinal fluid (CSF) concentrations of soluble B cell maturation antigen (sBCMA) and soluble CD27 (sCD27) have been shown to be sensitive biomarkers of inflammation in MS and are thought to reflect B and T cell activity, respectively. Furthermore, chitinase 3-like 1 (CHI3L1) and soluble CD14 (sCD14) have been suggested as measures of innate immune cell activity in MS. In this study we sought to validate measurements of these CSF biomarkers of inflammation using multiplex bead-based immunoassays.

METHODS

By using commercially available multiplex bead-based assays, concentrations of sBCMA, sCD27, sCD14 and CHI3L1 were determined in CSF from 22 patients with either untreated clinically isolated syndromes (CIS) or relapsing-remitting MS (RRMS), 13 patients with RRMS treated with either natalizumab or alemtuzumab, and 35 symptomatic controls (SC).

RESULTS

Increased CSF concentrations of sBCMA, sCD27 and CHI3L1 were observed in untreated MS patients compared to symptomatic controls (all p < 0.001). Concentrations of sBCMA (p = 0.02) and sCD27 (p = 0.0003) were higher in treated MS patients than in SC, and levels of sBCMA (p = 0.02) and sCD27 (p = 0.01) were even higher in untreated compared to treated patients. sCD14 levels did not differ between the groups. Levels of sBCMA and sCD27 correlated strongly with each other (Spearman's rho: 0.98, p < 0.0001) as well as with the IgG index (Spearman's rho: 0.91, p < 0.0001 and 0.90, p < 0.0001, respectively). ROC curve analysis showed a high discriminatory potential for sBCMA and sCD27 with areas under the curve of 0.88 and 0.93, respectively.

CONCLUSION

We confirm reports of elevated concentrations of sBCMA, sCD27 and CHI3L1 in CSF from untreated MS patients compared to SC. sBCMA and sCD27 levels were elevated in both treated and untreated MS patients compared to SC, but highest in untreated patients. Finally, CSF concentrations of sBCMA, sCD27 and the IgG index correlated strongly, suggesting that the cellular source of sCD27 and sBCMA includes memory B cells, plasmablasts and plasma cells.

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing Interest Mie Reith Mahler reports non-financial support from Merck for congress participation. Sophie Buhelt reports non-financial support from Merck and Biogen for congress participation. Finn Sellebjerg has served on scientific advisory boards, been on the steering committees of clinical trials, served as a consultant, received support for congress participation, received speaker honoraria, or received research support for his laboratory from Biogen, Merck, Novartis, Roche, Sanofi Genzyme and Teva. Helle Bach Søndergaard, Marina Rode von Essen, Jeppe Romme Christensen, and Christian Enevold have nothing to disclose.