A New Laboratory Workflow Integrating the Free Light Chains Kappa Quotient into Routine CSF Analysis

We performed this cohort study to test whether further analysis of intrathecal inflammation can be omitted if the free light chain kappa (FLCκ) quotient is within the reference range in the corresponding quotient diagram. FLCκ concentrations were measured in serum and cerebrospinal fluid (CSF) sampl...

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Main Authors: Malte Johannes Hannich, Mohammed R. Abdullah, Kathrin Budde, Astrid Petersmann, Matthias Nauck, Alexander Dressel, Marie Süße
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/12/11/1690
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author Malte Johannes Hannich
Mohammed R. Abdullah
Kathrin Budde
Astrid Petersmann
Matthias Nauck
Alexander Dressel
Marie Süße
author_facet Malte Johannes Hannich
Mohammed R. Abdullah
Kathrin Budde
Astrid Petersmann
Matthias Nauck
Alexander Dressel
Marie Süße
author_sort Malte Johannes Hannich
collection DOAJ
description We performed this cohort study to test whether further analysis of intrathecal inflammation can be omitted if the free light chain kappa (FLCκ) quotient is within the reference range in the corresponding quotient diagram. FLCκ concentrations were measured in serum and cerebrospinal fluid (CSF) samples. The intrathecal fraction (IF) of FLCκ was calculated in relation to the hyperbolic reference range. 679 patient samples were used as a discovery cohort (DC). The sensitivity and negative predictive value (NPV) of the FLCκ-IF for the detection of an intrathecal humoral immune response (CSF-specific OCB and/or IF IgG/A/M > 0%) was determined. Based on these data, a diagnostic algorithm was developed and prospectively validated in an independent validation cohort (VC, <i>n</i> = 278). The sensitivity of the FLCκ-IF was 98% in the DC and 97% in the VC with a corresponding NPV of 99%. The use of the FLCκ-IF as a first line analysis would have reduced the Ig and OCB analysis by 62% in the DC and 74% in the VC. The absence of a FLCκ-IF predicts the absence of a humoral intrathecal immune response with a very high NPV of 99%. Thus, integration of our proposed algorithm into routine CSF laboratory analysis could help to reduce analytical efforts.
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spelling doaj.art-9bf11a70768c41c28fbcd796c58c767d2023-11-24T07:47:50ZengMDPI AGBiomolecules2218-273X2022-11-011211169010.3390/biom12111690A New Laboratory Workflow Integrating the Free Light Chains Kappa Quotient into Routine CSF AnalysisMalte Johannes Hannich0Mohammed R. Abdullah1Kathrin Budde2Astrid Petersmann3Matthias Nauck4Alexander Dressel5Marie Süße6Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475 Greifswald, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475 Greifswald, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475 Greifswald, GermanyInstitute for Clinical Chemistry and Laboratory Medicine, University Oldenburg, 26133 Oldenburg, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Neurology, Carl-Thiem Klinikum Cottbus, 03048 Cottbus, GermanyDepartment of Neurology, University Medicine Greifswald, 17475 Greifswald, GermanyWe performed this cohort study to test whether further analysis of intrathecal inflammation can be omitted if the free light chain kappa (FLCκ) quotient is within the reference range in the corresponding quotient diagram. FLCκ concentrations were measured in serum and cerebrospinal fluid (CSF) samples. The intrathecal fraction (IF) of FLCκ was calculated in relation to the hyperbolic reference range. 679 patient samples were used as a discovery cohort (DC). The sensitivity and negative predictive value (NPV) of the FLCκ-IF for the detection of an intrathecal humoral immune response (CSF-specific OCB and/or IF IgG/A/M > 0%) was determined. Based on these data, a diagnostic algorithm was developed and prospectively validated in an independent validation cohort (VC, <i>n</i> = 278). The sensitivity of the FLCκ-IF was 98% in the DC and 97% in the VC with a corresponding NPV of 99%. The use of the FLCκ-IF as a first line analysis would have reduced the Ig and OCB analysis by 62% in the DC and 74% in the VC. The absence of a FLCκ-IF predicts the absence of a humoral intrathecal immune response with a very high NPV of 99%. Thus, integration of our proposed algorithm into routine CSF laboratory analysis could help to reduce analytical efforts.https://www.mdpi.com/2218-273X/12/11/1690cerebrospinal fluidfree light chain kappaimmunoglobulinlaboratory workflowprotein analytic
spellingShingle Malte Johannes Hannich
Mohammed R. Abdullah
Kathrin Budde
Astrid Petersmann
Matthias Nauck
Alexander Dressel
Marie Süße
A New Laboratory Workflow Integrating the Free Light Chains Kappa Quotient into Routine CSF Analysis
Biomolecules
cerebrospinal fluid
free light chain kappa
immunoglobulin
laboratory workflow
protein analytic
title A New Laboratory Workflow Integrating the Free Light Chains Kappa Quotient into Routine CSF Analysis
title_full A New Laboratory Workflow Integrating the Free Light Chains Kappa Quotient into Routine CSF Analysis
title_fullStr A New Laboratory Workflow Integrating the Free Light Chains Kappa Quotient into Routine CSF Analysis
title_full_unstemmed A New Laboratory Workflow Integrating the Free Light Chains Kappa Quotient into Routine CSF Analysis
title_short A New Laboratory Workflow Integrating the Free Light Chains Kappa Quotient into Routine CSF Analysis
title_sort new laboratory workflow integrating the free light chains kappa quotient into routine csf analysis
topic cerebrospinal fluid
free light chain kappa
immunoglobulin
laboratory workflow
protein analytic
url https://www.mdpi.com/2218-273X/12/11/1690
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