Highlights
- •Higher levels of sBCMA and sCD27 in cerebrospinal fluid in MS .
- •Levels of sBCMA, sCD27 and the IgG index correlate strongly.
- •sBCMA and sCD27 discriminate between untreated MS patients and symptomatic controls.
- •Elevated levels of sBCMA and sCD27 even in MS patients on high efficacy therapy.
Abstract
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.
Keywords
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Article info
Publication history
Published online: July 11, 2020
Accepted:
July 10,
2020
Received in revised form:
July 9,
2020
Received:
June 4,
2020
Identification
Copyright
© 2020 Elsevier B.V. All rights reserved.
