Abstract
Background and objectiveIn this study, we evaluated the diagnostic and prognostic significance of cerebrospinal fluid free light chains (CSF FLC) at the time of clinically isolated syndrome (CIS).MethodsWe compared FLC-parameters at the moment of CIS in patients with conversion to multiple sclerosis (MS) after 2 years (CIS-MS), patients who remained stable both clinically and radiologically after 2 years (CIS-nonMS), patients with non-inflammatory neurologic diseases (NIND) as a comparison group and patients with other inflammatory neurologic diseases (IND) with intrathecal oligoclonal bands (OCB) synthesis. ROC-analysis was conducted to define FLC-assay characteristics and cut-off values. We also compared FLC-concentrations in CIS patients to determine their OCB-status. A correlation analysis was performed between FLC-concentrations and the expanded disability scale score (EDSS), annualized relapse rate (ARR) and MRI-activity (i.e., number of new and gadolinium-enhancing (Gd+) lesions) in patients.ResultsThe levels of kappa-FLC (k-FLCCSF) and lambda-FLC (λ-FLCCSF) as well as kappa- and lambda-quotients (Q-k and Q-λ) were elevated in CIS-MS compared to the CIS-nonMS and NIND groups. These levels did not differ significantly when compared with the IND group. We identified several patients with high k-FLCCSF and λ-FLCCSF in OCB-negative CIS and IND groups. The level of k-FLCCSF production was significantly higher in OCB-positive patients in the CIS-MS group compared to the CIS-nonMS group. The concentrations of k-FLCCSF and Q-k in the CIS-MS group showed significant correlation with the level of EDSS after 2 years (k-FLC: r = 0.4477,p = 0.0016; Q-k: r = 0.4621, p = 0.0016). λ-FLCCSF and Q-λ inversely correlated with the number of Gd+ lesions (CSF λ-FLC: r = -0.3698, p = 0.0223; Q-λ: r = -0.4527, p = 0.0056).ConclusionThe concentration of CSF FLC predicts conversion to MS within 2 years following CIS. OCB-positive patients with an early conversion have a higher concentration of CSF-FLC. We have also shown a prognostic significance of k-FLCCSF for future EDSS-progression.
Highlights
Multiple sclerosis (MS) is a debilitating neurologic immune-mediated disease
The levels of kappa-free light chains (FLC) (k-FLCCSF) and lambda-FLC (λ-FLCCSF) as well as kappa- and lambda-quotients (Q-k and Q-λ) were elevated in clinically isolated syndrome (CIS)-MS compared to the CIS-nonMS and non-inflammatory neurologic diseases (NIND) groups
We have shown a prognostic significance of k-FLCCSF for future expanded disability scale score (EDSS)-progression
Summary
Multiple sclerosis (MS) is a debilitating neurologic immune-mediated disease. In the majority of patients, the condition begins as a single clinical episode, called clinically isolated syndrome (CIS). Potential prognostic biomarkers of conversion to CDMS could increase the clinical vigilance of MS and help define a potential therapeutic approach for patients with CIS. Increased intrathecal immunoglobulin (Ig) production and clonal restriction that result in the formation of IgG oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) are well described in both CIS and MS [1,2]. It has been shown that OCB detection at the time of CIS can predict the transformation to clinically definite MS [4]; this quantitative method cannot predict the rate of conversion and the range of disability among different patients with positive OCB-status. We evaluated the diagnostic and prognostic significance of cerebrospinal fluid free light chains (CSF FLC) at the time of clinically isolated syndrome (CIS)
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