Kappa free light chain index as a diagnostic biomarker in multiple sclerosis: A real‐world investigation

Abstract

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The Increasing Role of Kappa Free Light Chains in the Diagnosis of Multiple Sclerosis

“…Studies using isoelectric focusing and consecutive silver staining in polyacrylamide gels for the determination of OCB reached a diagnostic sensitivity of about 99% in MS patients, which was superior to KFLC measurement [24,27,42]. However, a similar procedure for OCB determination conducted at a different laboratory site reached a diagnostic sensitivity of 89% in MS patients, indicating the dependency of conductor and rater of non-automated determination methods [43]. Studies included in this review used immunofixation, immunoblotting, or Western blotting assays for OCB determination.…”

“…Over all studies, the mean prevalence of OCB positivity in MS patients was 94% (min-max: 85-100%) reflecting the importance of detection of intrathecal inflammation as a criterion for dissemination in time [24,[26][27][28][29]33,[42][43][44]47,48,55,56,[68][69][70][71][72][73][74][75]92]. Nevertheless, it has to be considered that some studies only included OCB-positive MS patients while other studies comprised a certain percentage of OCB-negative MS patients, thus leading the observed wide range of OCB prevalence [24,[26][27][28][29]33,[42][43][44]47,48,55,56,[68][69][70][71][72][73][74][75]92]. KFLC measurements, interpreted by different approaches, reached a mean diagnostic sensitivity of 94% (min-max: 72-100%) and specificity of 84% (min-max: 65-100%) in MS patients [24,…”

“…The investigation of KFLC under therapy with interferons (IFNβ-1a) showed stable concentrations in CSF over a two-year time course [77]. Rosenstein et al could not observe significant changes of KFLC indices in patients treated with fingolimod or alemtuzumab when baseline levels and values after 12 or 24 months were compared [43].…”

“…In a cohort consisting of 100 MS patients, 24 CIS patients with conversion to MS and 44 CIS patients without conversion to MS, the diagnostic superiority of Reiber's diagram for KFLC was shown [24]. Reiber's diagram was applied in further studies and a diagnostic sensitivity of 97% (94%, 99%) and specificity of 75% (53%, 97%) was reported [24][25][26][27][28][29]43,68,75]. Further, Süße et al used Reiber's diagram to determine a cut-off value based on the intrathecal fraction of KFLC (KFLC IF according to Reiber's diagram) in order to differentiate between neuromyelitis optica spectrum disorders (NMOSD) and MS [25,26].…”

“…Thus, studies, which applied the revised McDonald criteria of 2017 in order to evaluate the performance of KFLC in the diagnosis of MS and CIS, constitute the most relevant investigations for this review (Tables 3 and 4) [16]. Over all studies, the mean prevalence of OCB positivity in MS patients was 94% (min-max: 85-100%) reflecting the importance of detection of intrathecal inflammation as a criterion for dissemination in time [24,[26][27][28][29]33,[42][43][44]47,48,55,56,[68][69][70][71][72][73][74][75]92]. Nevertheless, it has to be considered that some studies only included OCB-positive MS patients while other studies comprised a certain percentage of OCB-negative MS patients, thus leading the observed wide range of OCB prevalence [24,[26][27][28][29]33,[42][43][44]47,48,55,56,[68][69][70][71][72][73][74][75]…”