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Sample Preparation for Endopeptidomic Analysis in Human Cerebrospinal Fluid
Published on: December 4, 2017
Kappa free light chains in cerebrospinal fluid to identify patients with oligoclonal bands
M Süße1, M Hannich2, A Petersmann2
1Department of Neurology, University Medicine Greifswald, Greifswald.
Insights
The kappa free light chains (KFLC) index can accurately predict oligoclonal bands (OCB), a marker for intrathecal immunoglobulin synthesis. This quantitative measure offers a potential initial diagnostic step for central nervous system disorders.
Area of Science:
- Neurology
- Immunology
- Clinical Diagnostics
Background:
- Oligoclonal bands (OCB) are the gold standard for detecting intrathecal immunoglobulin synthesis.
- The kappa free light chains (KFLC) index demonstrates comparable sensitivity and specificity to OCB in multiple sclerosis diagnosis.
Purpose of the Study:
- To investigate the predictive value of the KFLC index for the presence of OCB.
- To evaluate the KFLC index as a potential initial diagnostic tool for central nervous system inflammatory disorders.
Main Methods:
- Prospective determination of the KFLC index in 295 paired serum and cerebrospinal fluid samples (cohort I).
- Nephelometry was used for KFLC determination, with a cut-off value established via ROC analysis.
- Validation in 96 samples (cohort II) and retrospective analysis of 46 OCB-positive patients (cohort III).
- Comparison of two commercial KFLC nephelometric assays.
Main Results:
- A KFLC index cut-off of 3.61 achieved 100% sensitivity and 88% specificity in cohort I.
- Prospective validation showed 92% sensitivity and 96% specificity.
- Retrospective analysis (cohort III) yielded 93% sensitivity.
- Good agreement (r² = 0.86) was observed between two KFLC assays.
Conclusions:
- The KFLC index, with a cut-off of 3.61, accurately predicts immunoglobulin G synthesis detected by OCB analysis.
- KFLC index determination offers a quantitative parameter suitable as an initial diagnostic step for inflammatory CNS disorders prior to OCB measurement.
Background And Purpose:
The gold standard for detection of intrathecal immunoglobulin synthesis is the measurement of oligoclonal bands (OCB). In the diagnosis of multiple sclerosis, the kappa free light chains (KFLC) index has a similar sensitivity and specificity as OCB. This study investigated whether determination of the KFLC index could be used to predict the presence of OCB.
Methods:
The KFLC index was determined prospectively from 295 paired serum and cerebrospinal fluid samples. KFLC were determined by nephelometry using the N Latex FLC kappa kit (Siemens Healthcare Diagnostics Products GmbH) on the BN Prospec analyzer (Siemens Healthcare Diagnostics Products GmbH) (cohort I). A cut-off value was determined using receiver operating characteristic analysis in relation to OCB positivity. These results were validated prospectively in 96 samples (cohort II) as well as retrospectively in samples of 46 patients known to be OCB positive (cohort III). We also compared the agreement of two commercially available nephelometric KFLC assays.
Results:
In cohort I, a KFLC index of 3.61 yielded 100% sensitivity and 88% specificity. Prospective validation of this cut-off value in cohort II showed 92% sensitivity and 96% specificity. In cohort III, a sensitivity of 93% was achieved. Comparison of Siemens and Binding Site (Birmingham, UK) assays revealed good agreement (r2 = 0.86).
Conclusions:
The KFLC index with a cut-off value of 3.61 had high diagnostic accuracy to predict immunoglobulin G synthesis via OCB analysis. Determination of the KFLC index provided a quantitative parameter that could be used as an initial diagnostic step in inflammatory central nervous system disorders before measuring OCB.
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