Cerebrospinal fluid and urinary biomarkers in multiple sclerosis.

OBJECTIVES

Biomarkers with the potential for longitudinal measurements are needed in multiple sclerosis (MS). Urine is easy to collect, and repeated sampling is possible.

METHODS

39 paired CSF and urine samples were taken. Oligoclonal bands (OCBs) were measured in CSF. Kappa and lambda free light chain (FLC), neopterin and ubiquitin C-terminal hydrolase-L1 (UCHL1) were measured in CSF and urine.

RESULTS

16/39 samples had OCBs unique to the CSF. CSF FLC levels (P < 0.0001) were higher in OCB-positive subjects, with no difference in urinary FLC. CSF and urinary FLC did not correlate. There were a significant correlation between total CSF FLC and CSF neopterin in MS samples (correlation coefficient = 0.588, P = 0.016) and a strong correlation between CSF lambda FLC and CSF neopterin in MS samples (correlation coefficient = 0.875, P < 0.001). There was a strong correlation between urinary neopterin/creatinine levels and urinary total FLC/protein levels (correlation coefficient = 0.452, P = 0.004). Only three CSF samples (8%) had detectable levels of UCHL1. 18/38 (48%) (8/15 MS and 10/23 control) urine samples had detectable levels of UCLH1.

CONCLUSIONS

This study confirms the relationship between CSF OCBs and CSF FLCs, highlighting the importance of intrathecal B- and plasma-cell activation in MS. There is a relationship between CSF FLC and CSF neopterin in MS, highlighting the multifaceted immune activation seen in MS. Correlations in the OCB-positive group highlight the multifaceted immune activation seen in MS. Further studies are required to evaluate CSF and urinary biomarkers.