title: Assessment of Intrathecal Free Light Chain Synthesis: Comparison of Different Quantitative Methods with the Detection of Oligoclonal Free Light Chains by Isoelectric Focusing and Affinity-Mediated Immunoblotting.
abstract: OBJECTIVE
  We aimed to compare various methods for free light chain (fLC) quantitation in cerebrospinal fluid (CSF) and serum and to determine whether quantitative CSF measurements could reliably predict intrathecal fLC synthesis. In addition, we wished to determine the relationship between free kappa and free lambda light chain concentrations in CSF and serum in various disease groups.
  
  
  METHODS
  We analysed 166 paired CSF and serum samples by at least one of the following methods: turbidimetry (Freelite™, SPAPLUS), nephelometry (N Latex FLC™, BN ProSpec), and two different (commercially available and in-house developed) sandwich ELISAs. The results were compared with oligoclonal fLC detected by affinity-mediated immunoblotting after isoelectric focusing.
  
  
  RESULTS
  Although the correlations between quantitative methods were good, both proportional and systematic differences were discerned. However, no major differences were observed in the prediction of positive oligoclonal fLC test. Surprisingly, CSF free kappa/free lambda light chain ratios were lower than those in serum in about 75% of samples with negative oligoclonal fLC test. In about a half of patients with multiple sclerosis and clinically isolated syndrome, profoundly increased free kappa/free lambda light chain ratios were found in the CSF.
  
  
  CONCLUSIONS
  Our results show that using appropriate method-specific cut-offs, different methods of CSF fLC quantitation can be used for the prediction of intrathecal fLC synthesis. The reason for unexpectedly low free kappa/free lambda light chain ratios in normal CSFs remains to be elucidated. Whereas CSF free kappa light chain concentration is increased in most patients with multiple sclerosis and clinically isolated syndrome, CSF free lambda light chain values show large interindividual variability in these patients and should be investigated further for possible immunopathological and prognostic significance.
authors.affiliation: Institute of Laboratory Diagnostics, University Hospital Ostrava, 17. listopadu 1790, 708 52 Ostrava-Poruba, Czech Republic.|Clinic of Neurology, University Hospital Ostrava, 17. listopadu 1790, 708 52 Ostrava-Poruba, Czech Republic.
authors.forename: David
authors.identifier: http://orcid.org/0000-0001-6822-2572
authors.initials: D
authors.lastname: Zeman
authors.affiliation: Institute of Laboratory Diagnostics, University Hospital Ostrava, 17. listopadu 1790, 708 52 Ostrava-Poruba, Czech Republic.
authors.forename: Pavlína
authors.initials: P
authors.lastname: Kušnierová
authors.affiliation: Institute of Laboratory Diagnostics, University Hospital Ostrava, 17. listopadu 1790, 708 52 Ostrava-Poruba, Czech Republic.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Švagera
authors.affiliation: Institute of Laboratory Diagnostics, University Hospital Ostrava, 17. listopadu 1790, 708 52 Ostrava-Poruba, Czech Republic.
authors.forename: František
authors.initials: F
authors.lastname: Všianský
authors.affiliation: Institute for Healthcare Disciplines, St. Elisabeth University of Health and Social Work in Bratislava, Palackého 1, P.O. Box 104, 810 00 Bratislava, Slovak Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Byrtusová
authors.affiliation: Clinic of Neurology, University Hospital Ostrava, 17. listopadu 1790, 708 52 Ostrava-Poruba, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Hradílek
authors.affiliation: Clinic of Neurology, University Hospital Ostrava, 17. listopadu 1790, 708 52 Ostrava-Poruba, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Kurková
authors.affiliation: Clinic of Neurology, University Hospital Ostrava, 17. listopadu 1790, 708 52 Ostrava-Poruba, Czech Republic.
authors.forename: Olga
authors.initials: O
authors.lastname: Zapletalová
authors.affiliation: Institute of Laboratory Diagnostics, University Hospital Ostrava, 17. listopadu 1790, 708 52 Ostrava-Poruba, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Bartoš
mesh_terms: D016022:Case-Control Studies; D003711:Demyelinating Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D004797:Enzyme-Linked Immunosorbent Assay / Q000295:instrumentation / Q000379:methods; D006801:Humans; D015151:Immunoblotting / Q000295:instrumentation / Q000379:methods; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis* / Q000097:blood / Q000134:cerebrospinal fluid; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis* / Q000097:blood / Q000134:cerebrospinal fluid; D007525:Isoelectric Focusing / Q000295:instrumentation / Q000379:methods; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D009391:Nephelometry and Turbidimetry / Q000295:instrumentation / Q000379:methods; D015588:Observer Variation; D012372:ROC Curve; D015203:Reproducibility of Results
chemical_list: D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains