Application of κ Free Light Chains in Cerebrospinal Fluid as a Biomarker in Multiple Sclerosis Diagnosis: Development of a Diagnosis Algorithm

Clin Chem Lab Med. 2018 Mar 28;56(4):609-613. doi: 10.1515/cclm-2017-0285.

Abstract

Background: The determination of κ free light chains (KFLC) in cerebrospinal fluid (CSF) by nephelometry is a feasible alternative to immunoglobulin G oligoclonal bands (OCB) in the evaluation of intrathecal synthesis of immunoglobulin in multiple sclerosis (MS) and other demyelinating diseases. The aim of this study was to assess the diagnostic value of KFLC and its inclusion in a procedure algorithm along with OCB interpretation.

Methods: A cross-sectional study, which included 123 patients with a CSF OCB request, was carried out. Isoelectric focusing followed by immunofixation was used to detect OCB, and nephelometry was used to analyze KFLC. The KFLC index was calculated using CSF/serum quotient of KFLC and albumin. The KFLC index was compared with MS diagnosis to find the optimal cutoff. It was obtained from the receiver operating characteristic (ROC) curves and the Youden method.

Results: The CSF KFLC median was 1.66 mg/L in the MS group, whereas in other central nervous system diseases, KFLC showed generally no or only moderate increase in CSF (median 0.10 mg/L). KFLC index showed a significant difference between groups. ROC analysis for CSF KFLC concentration, and KFLC indexes were 91.88% and 93.94%, respectively. The best cutoff for the KFLC index was 2.91 for MS diagnosis (sensitivity: 83.78%; specificity: 85.88%). The proposed algorithm showed high sensitivity (89.19%) and specificity (84.71%).

Conclusions: KFLC determination is rapid and automatized, but it has no higher sensitivity and specificity than OCB in MS diagnosis. Nevertheless, when used in screening, it could reduce the number of manual OCB tests.

Keywords: cerebrospinal fluid; diagnosis; free light chains; intrathecal synthesis; multiple sclerosis.

MeSH terms

  • Algorithms*
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Cross-Sectional Studies
  • Humans
  • Immunoglobulin kappa-Chains / blood
  • Immunoglobulin kappa-Chains / cerebrospinal fluid*
  • Immunologic Tests
  • Isoelectric Focusing
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / cerebrospinal fluid*
  • Multiple Sclerosis / diagnosis*
  • Nephelometry and Turbidimetry
  • Sensitivity and Specificity

Substances

  • Biomarkers
  • Immunoglobulin kappa-Chains