Abstract
ObjectivesWe 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.MethodsWe 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.ResultsAlthough 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.ConclusionsOur 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.
Highlights
The presence of free kappa light chains in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients was already assumed in 1974 [1], only recently had they been widely advocated as a tool in the laboratory support of MS diagnosis or to estimate the probability of developing MS in patients after the first demyelinating event, the so-called clinically isolated syndrome (CIS) [2,3,4,5,6,7,8,9,10]
Our results show that using appropriate method-specific cut-offs, different methods of CSF free light chain (fLC) quantitation can be used for the prediction of intrathecal fLC synthesis
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
Summary
The presence of free kappa light chains (fKLC) in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients was already assumed in 1974 [1], only recently had they been widely advocated as a tool in the laboratory support of MS diagnosis or to estimate the probability of developing MS in patients after the first demyelinating event, the so-called clinically isolated syndrome (CIS) [2,3,4,5,6,7,8,9,10]. Already in the 1980s and 1990s, several qualitative [11,12,13,14,15,16,17] and quantitative [18,19,20,21,22] methods were introduced for the assessment of free kappa (fKLC) as well as lambda (fLLC) light chains in the CSF, but none of them have reached wide acceptance due to labouriousness and possibly lack of standardisation. The development of turbidimetric/nephelometric free light chain (fLC) assays for serum analysis [23] and subsequent introduction of these tests into clinical practice for the diagnosis and monitoring of patients with plasma cell dyscrasias at the beginning of the 21st century [24, 25] opened a more convenient way to fLC quantitation in serum and urine, and in CSF. The same is hopefully expected in the near future for N Latex FLC kits by Siemens introduced for serum fLC measurement in 2011 [28]
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