Abstract
BackgroundQuantification of kappa free light chains (KFLC) in cerebrospinal fluid shows high diagnostic sensitivity in multiple sclerosis and clinically isolated syndrome patients. However, a clearly defined threshold value is still missing and a possible prognostic value of the KFLC levels in these patients remains undefined.MethodsResults of KFLC quantification in 420 controls were used to set an upper limit of normal KFLC concentration in CSF under different blood-CSF-barrier conditions. Additionally, KFLC values of MS and CIS patients were assessed and results were evaluated with reference to the patients corresponding disease courses.ResultsThe calculated upper limit of normal KFLC-concentration covers 98% of these control patients. Using this cut-off, plasma cell activity in CSF can be detected in 97% of MS patients and in 97% of CIS patients. However, there is no evidence that the extent of KFLC elevation provides prognostic value in MS and CIS patients in this study.ConclusionKFLC determination should become a first line screen in the diagnostic algorithms of MS and CIS. The extent of elevation of intrathecal KFLC has no prognostic value on the disease course in MS and CIS patients.
Highlights
The detection of a humoral immune response by CSF analysis supports the diagnostic process in cases of MS and CIS[1,2,3]
The intra-assay tests showed low variations when measuring the minor concentrations of kappa free light chains (KFLC) that were regularly found in CSF, with coefficient of variation (CV) of 4,0% for 0,1 mg/l, 3,4% for 0,2 mg/l, 3,7% for 0,4 mg/l and 2,9% for 0,8 mg/l
The threshold line constructed by using the mean value of KFLC-ratio (KFLC in CSF divided by KFLC in serum) +36 standard deviation of each subcohort covered 412 patients (98%) of our control group
Summary
The detection of a humoral immune response by CSF analysis supports the diagnostic process in cases of MS and CIS[1,2,3] In those patients, plasma cells located in the intrathecal space secrete predominantly IgG and the quantitative and qualitative determination of this marker is part of current generally accepted diagnostic criteria of MS [4]. The current gold standard test for the qualitative demonstration of oligoclonal IgG in the CSF is isoelectric focusing (IEF) followed by immunoblotting [8] This demanding method of oligoclonal bands (OB) determination reached high sensitivities (88–100%) in several studies in MS patients [9,10,11]. A clearly defined threshold value is still missing and a possible prognostic value of the KFLC levels in these patients remains undefined
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