Free light chain monomer-dimer patterns in the diagnosis of multiple sclerosis

Batia Kaplan, Sizilia Golderman, Gilad Yahalom, Regina Yeskaraev, Tamar Ziv, Boris M. Aizenbud, Ben Ami Sela, Avi Livneh

Research output: Contribution to journalArticlepeer-review

Abstract

In our search of new biomarkers for multiple sclerosis (MS), we aimed to characterize the immunoglobulin (Ig) free light chains (FLC) in patients' cerebrospinal fluid (CSF) and serum, and to evaluate the diagnostic utility of FLC monomer-dimer patterns for MS. FLC were analyzed by Western blotting and mass spectroscopy. CSF and serum samples were examined for the presence of oligoclonal Ig bands by a conventional laboratory test for MS. Three distinct pathological FLC monomer-dimer patterns, typical of MS but not of other neurological diseases, were revealed. In 31 out 56 MS patients the highly increased CSF levels of κ monomers and dimers were demonstrated. In 18 MS patients, the increased κ-FLC levels were accompanied by highly elevated λ dimers. Five MS cases showed no significant elevation in κ-FLC, but they displayed abnormally high λ dimer levels. The intensity of the immunoreactive FLC bands was measured to account for κ and λ monomer and dimer levels and their ratios in the CSF and serum. Combined usage of different FLC parameters allowed the determination of the appropriate FLC threshold values to diagnose MS. The developed method showed higher sensitivity and specificity (96% and 90%, respectively), as compared to those of the conventional OCB test (82% and 70%, respectively). Our study highlights the role of the differential analysis of monomeric and dimeric κ- and λ-FLC for the precise diagnosis of MS.

Original languageEnglish
Pages (from-to)74-80
Number of pages7
JournalJournal of Immunological Methods
Volume390
Issue number1-2
DOIs
StatePublished - 30 Apr 2013

Keywords

  • Cerebrospinal fluid
  • Diagnosis
  • Free light chains
  • Mass spectrometry
  • Multiple sclerosis
  • Western blotting

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