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Inter-assay diagnostic accuracy of cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis

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Abstract
Background: Cerebrospinal fluid (CSF) kappa free light chain (kappa FLC) measures gained increasing interest as diagnostic markers in multiple sclerosis (MS). However, the lack of studies comparing assay-dependent diagnostic cutoff values hinders their use in clinical practice. Additionally, the optimal kappa FLC parameter for identifying MS remains a subject of ongoing debate. Objectives: The aim of this study was to compare same-sample diagnostic accuracies of the kappa FLC index, kappa IgG index, CSF kappa FLC/IgG ratio, and isolated CSF kappa FLC (iCSF-kappa FLC) between two reference centers using different methods. Methods: Paired serum and CSF samples were analyzed for kappa FLC and albumin concentrations by Freelite (R)-Optilite (Sint-Jan Bruges hospital) and N Latex (R)-BNII (Ghent University hospital). Diagnostic performance to differentiate MS from controls was assessed using ROC curve analysis. Results: A total of 263 participants were included (MS, n = 80). Optimal diagnostic cutoff values for the kappa FLC index (Freelite (R)-Optilite: 7.7; N Latex (R)-BNII: 4.71), kappa IgG index (Freelite (R)-Optilite: 14.15, N Latex (R)-BNII: 12.19), and CSF kappa FLC/IgG ratio (Freelite (R)-Optilite: 2.27; N Latex (R)-BNII: 1.44) differed between the two methods. Sensitivities related to optimal cutoff values were 89.9% (Freelite (R)-Optilite) versus 94.6% (N Latex (R)-BNII) for the kappa FLC index, 91% (Freelite (R)-Optilite) versus 92.2% (N Latex (R)-BNII) for the kappa IgG index, and 81.3% (Freelite (R)-Optilite) versus 91.4% (N Latex (R)-BNII) for the CSF kappa FLC/IgG ratio. However, for iCSF-kappa FLC, optimal diagnostic cutoff values (0.36 mg/L) and related specificities (81.8%) were identical with a related diagnostic sensitivity of 89.9% for Freelite (R)-Optilite and 90.5% for N Latex (R)-BNII. The diagnostic performance of the kappa FLC index [area under the curve (AUC) Freelite (R)-Optilite: 0.924; N Latex (R)-BNII: 0.962] and kappa IgG index (AUC Freelite (R)-Optilite: 0.929; N Latex (R)-BNII: 0.961) was superior compared to CSF oligoclonal bands (AUC: 0.898, sensitivity: 83.8%, specificity: 95.9%). Conclusions: The kappa FLC index and the kappa IgG index seem to be excellent markers for identifying MS, irrespective of the method used for kappa FLC quantification. Based on the AUC, they appear to be the measures of choice. For all measures, optimal cutoff values differed between methods except for iCSF-kappa FLC. iCSF-kappa FLC might therefore serve as a method-independent, more cost-efficient, initial screening measure for MS. These findings are particularly relevant for clinical practice given the potential future implementation of intrathecal kappa FLC synthesis in MS diagnostic criteria and for future multicentre studies pooling data on kappa FLC measures.
Keywords
Freelite (R)-Optilite versus N Latex (R)-BNII, CSF kappa FLC/IgG ratio, kappa IgG index, kappa FLC index, kappa free light chains, multiple sclerosis

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MLA
Dekeyser, Cathérine, et al. “Inter-Assay Diagnostic Accuracy of Cerebrospinal Fluid Kappa Free Light Chains for the Diagnosis of Multiple Sclerosis.” FRONTIERS IN IMMUNOLOGY, vol. 15, 2024, doi:10.3389/fimmu.2024.1385231.
APA
Dekeyser, C., De Kesel, P., Cambron, M., Vanopdenbosch, L., Van Hijfte, L., Vercammen, M., & Laureys, G. (2024). Inter-assay diagnostic accuracy of cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis. FRONTIERS IN IMMUNOLOGY, 15. https://doi.org/10.3389/fimmu.2024.1385231
Chicago author-date
Dekeyser, Cathérine, Pieter De Kesel, Melissa Cambron, Ludo Vanopdenbosch, Liesbeth Van Hijfte, Martine Vercammen, and Guy Laureys. 2024. “Inter-Assay Diagnostic Accuracy of Cerebrospinal Fluid Kappa Free Light Chains for the Diagnosis of Multiple Sclerosis.” FRONTIERS IN IMMUNOLOGY 15. https://doi.org/10.3389/fimmu.2024.1385231.
Chicago author-date (all authors)
Dekeyser, Cathérine, Pieter De Kesel, Melissa Cambron, Ludo Vanopdenbosch, Liesbeth Van Hijfte, Martine Vercammen, and Guy Laureys. 2024. “Inter-Assay Diagnostic Accuracy of Cerebrospinal Fluid Kappa Free Light Chains for the Diagnosis of Multiple Sclerosis.” FRONTIERS IN IMMUNOLOGY 15. doi:10.3389/fimmu.2024.1385231.
Vancouver
1.
Dekeyser C, De Kesel P, Cambron M, Vanopdenbosch L, Van Hijfte L, Vercammen M, et al. Inter-assay diagnostic accuracy of cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis. FRONTIERS IN IMMUNOLOGY. 2024;15.
IEEE
[1]
C. Dekeyser et al., “Inter-assay diagnostic accuracy of cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis,” FRONTIERS IN IMMUNOLOGY, vol. 15, 2024.
@article{01HZ1KZ89VAFP2S6JVXQM99650,
  abstract     = {{Background: Cerebrospinal fluid (CSF) kappa free light chain (kappa FLC) measures gained increasing interest as diagnostic markers in multiple sclerosis (MS). However, the lack of studies comparing assay-dependent diagnostic cutoff values hinders their use in clinical practice. Additionally, the optimal kappa FLC parameter for identifying MS remains a subject of ongoing debate. Objectives: The aim of this study was to compare same-sample diagnostic accuracies of the kappa FLC index, kappa IgG index, CSF kappa FLC/IgG ratio, and isolated CSF kappa FLC (iCSF-kappa FLC) between two reference centers using different methods. Methods: Paired serum and CSF samples were analyzed for kappa FLC and albumin concentrations by Freelite (R)-Optilite (Sint-Jan Bruges hospital) and N Latex (R)-BNII (Ghent University hospital). Diagnostic performance to differentiate MS from controls was assessed using ROC curve analysis. Results: A total of 263 participants were included (MS, n = 80). Optimal diagnostic cutoff values for the kappa FLC index (Freelite (R)-Optilite: 7.7; N Latex (R)-BNII: 4.71), kappa IgG index (Freelite (R)-Optilite: 14.15, N Latex (R)-BNII: 12.19), and CSF kappa FLC/IgG ratio (Freelite (R)-Optilite: 2.27; N Latex (R)-BNII: 1.44) differed between the two methods. Sensitivities related to optimal cutoff values were 89.9% (Freelite (R)-Optilite) versus 94.6% (N Latex (R)-BNII) for the kappa FLC index, 91% (Freelite (R)-Optilite) versus 92.2% (N Latex (R)-BNII) for the kappa IgG index, and 81.3% (Freelite (R)-Optilite) versus 91.4% (N Latex (R)-BNII) for the CSF kappa FLC/IgG ratio. However, for iCSF-kappa FLC, optimal diagnostic cutoff values (0.36 mg/L) and related specificities (81.8%) were identical with a related diagnostic sensitivity of 89.9% for Freelite (R)-Optilite and 90.5% for N Latex (R)-BNII. The diagnostic performance of the kappa FLC index [area under the curve (AUC) Freelite (R)-Optilite: 0.924; N Latex (R)-BNII: 0.962] and kappa IgG index (AUC Freelite (R)-Optilite: 0.929; N Latex (R)-BNII: 0.961) was superior compared to CSF oligoclonal bands (AUC: 0.898, sensitivity: 83.8%, specificity: 95.9%). Conclusions: The kappa FLC index and the kappa IgG index seem to be excellent markers for identifying MS, irrespective of the method used for kappa FLC quantification. Based on the AUC, they appear to be the measures of choice. For all measures, optimal cutoff values differed between methods except for iCSF-kappa FLC. iCSF-kappa FLC might therefore serve as a method-independent, more cost-efficient, initial screening measure for MS. These findings are particularly relevant for clinical practice given the potential future implementation of intrathecal kappa FLC synthesis in MS diagnostic criteria and for future multicentre studies pooling data on kappa FLC measures.}},
  articleno    = {{1385231}},
  author       = {{Dekeyser, Cathérine and De Kesel, Pieter and Cambron, Melissa and Vanopdenbosch, Ludo and Van Hijfte, Liesbeth and Vercammen, Martine and Laureys, Guy}},
  issn         = {{1664-3224}},
  journal      = {{FRONTIERS IN IMMUNOLOGY}},
  keywords     = {{Freelite (R)-Optilite versus N Latex (R)-BNII,CSF kappa FLC/IgG ratio,kappa IgG index,kappa FLC index,kappa free light chains,multiple sclerosis}},
  language     = {{eng}},
  pages        = {{15}},
  title        = {{Inter-assay diagnostic accuracy of cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis}},
  url          = {{http://doi.org/10.3389/fimmu.2024.1385231}},
  volume       = {{15}},
  year         = {{2024}},
}

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