Elevated levels of kappa free light chains in CSF support the diagnosis of multiple sclerosis

J Neurol. 2008 Oct;255(10):1508-14. doi: 10.1007/s00415-008-0954-z. Epub 2008 Jul 17.

Abstract

Background: Numerous studies have demonstrated elevated kappa free light chains (KFLCs) in CSF of multiple sclerosis (MS) patients. However, so far only small cohorts have been examined, and generally only through qualitative KFLCs analysis. Using a recently developed free light chain (FLC) immunoassay, it is now possible to quantitatively measure KFLCs by automated nephelometry. Our objective was to determine the extent to which KFLC levels in CSF correlated with the diagnosis of MS and CISSMS (clinically isolated syndrome suggestive of MS) compared to oligoclonal banding (OCB) and the immunoglobulin G (IgG) index.

Methods: CSF and serum samples from 438 unselected patients, including a MS group of 70 patients (41 MS, 29 CISSMS), were analysed using nephelometry and isoelectric focusing. We then retrospectively correlated results with patients' diagnoses.

Results: Of the MS group (n = 70), 67 patients had elevated KFLCs using the KFLC index (> or = 5.9), 64 patients showed OCB and 56 patients presented with an elevated IgG index (> or = 0.6). Sensitivities were 0.96 for the KFLC index, 0.91 for OCB and 0.80 for the IgG index. The specificity of the KFLC index for the MS group (0.86) was lower than that of OCB (0.92) but distinctly higher compared to the IgG index (0.77).

Conclusion: In this study, an elevated KFLC-index represented the most sensitive and specific quantitative diagnostic parameter for MS. As it is measured by automated, routinely available laboratory methods, KFLC quantitation can provide a rapid and reproduceable indication of intrathecal immunological processes supporting current MS diagnostic criteria.

MeSH terms

  • Demyelinating Diseases / cerebrospinal fluid
  • Demyelinating Diseases / diagnosis*
  • Humans
  • Immunoassay
  • Immunoglobulin G / blood
  • Immunoglobulin G / cerebrospinal fluid
  • Immunoglobulin kappa-Chains / blood
  • Immunoglobulin kappa-Chains / cerebrospinal fluid*
  • Immunoglobulin lambda-Chains / blood
  • Immunoglobulin lambda-Chains / cerebrospinal fluid
  • Isoelectric Focusing
  • Multiple Sclerosis / cerebrospinal fluid
  • Multiple Sclerosis / diagnosis*
  • Nephelometry and Turbidimetry
  • Oligoclonal Bands / blood
  • Oligoclonal Bands / cerebrospinal fluid

Substances

  • Immunoglobulin G
  • Immunoglobulin kappa-Chains
  • Immunoglobulin lambda-Chains
  • Oligoclonal Bands