Diagnostic and Prognostic Value of the Cerebrospinal Fluid Concentration of Immunoglobulin Free Light Chains in Clinically Isolated Syndrome with Conversion to Multiple Sclerosis

PLoS One. 2015 Nov 25;10(11):e0143375. doi: 10.1371/journal.pone.0143375. eCollection 2015.

Abstract

Background and objective: In 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).

Methods: We 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.

Results: The 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).

Conclusion: The 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.

MeSH terms

  • Adult
  • Age of Onset
  • Case-Control Studies
  • Female
  • Humans
  • Immunoglobulin Light Chains / cerebrospinal fluid*
  • Immunoglobulin Light Chains / immunology
  • Immunoglobulin kappa-Chains / cerebrospinal fluid
  • Immunoglobulin lambda-Chains / cerebrospinal fluid
  • Male
  • Multiple Sclerosis / cerebrospinal fluid*
  • Multiple Sclerosis / diagnosis*
  • Multiple Sclerosis / immunology
  • Prognosis
  • ROC Curve
  • Young Adult

Substances

  • Immunoglobulin Light Chains
  • Immunoglobulin kappa-Chains
  • Immunoglobulin lambda-Chains

Grant support

The authors received no specific funding for this work.