Validation of kappa free light chains as a diagnostic biomarker in multiple sclerosis and clinically isolated syndrome: A multicenter study

Mult Scler. 2016 Apr;22(4):502-10. doi: 10.1177/1352458515594044. Epub 2015 Jul 21.


Background: Kappa free light chains (KFLCs) have been proposed as a diagnostic biomarker in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS).

Objective: The objective of this paper is to validate the diagnostic accuracy of intrathecal KFLC synthesis in a multicenter study.

Methods: KFLCs were measured by nephelometry under blinded conditions in cerebrospinal fluid (CSF) and serum sample pairs of patients with CIS (n = 60), MS (n = 60) and other neurological diseases (n = 60) from four different MS centers. The upper normal limit for intrathecal KFLC concentrations depending on blood-CSF barrier function was previously calculated in a cohort of 420 control patients.

Results: Diagnostic sensitivity of intrathecal KFLC synthesis, IgG synthesis according to Reiber, IgG index and oligoclonal bands (OCBs) was 95%, 72%, 73% and 93% in patients with MS and 82%, 47%, 43% and 72% in patients with CIS. Specificity of intrathecal KFLC synthesis was 95% and 98% for all other measures.

Conclusion: These findings further support the diagnostic value of intrathecal KFLC synthesis in CIS and MS patients and demonstrate a valid, easier and rater-independent alternative to OCB detection.

Keywords: IgG index; Kappa free light chain; cerebrospinal fluid; clinically isolated syndrome; intrathecal IgG synthesis; multiple sclerosis; oligoclonal bands; serum.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Austria
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Cross-Sectional Studies
  • Demyelinating Diseases / blood
  • Demyelinating Diseases / cerebrospinal fluid
  • Demyelinating Diseases / diagnosis*
  • Demyelinating Diseases / immunology
  • Female
  • Germany
  • Humans
  • Immunoglobulin kappa-Chains / blood
  • Immunoglobulin kappa-Chains / cerebrospinal fluid*
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / cerebrospinal fluid
  • Multiple Sclerosis / diagnosis*
  • Multiple Sclerosis / immunology
  • Nephelometry and Turbidimetry
  • Predictive Value of Tests
  • Reproducibility of Results
  • Young Adult


  • Biomarkers
  • Immunoglobulin kappa-Chains