Improving the efficiency of free kappa light chains as diagnostic biomarker of Multiple Sclerosis by using a novel algorithm

•The combined use of certain algorithms involving index of free kappa light chains along with oligoclonal IgG bands and other calculations can increase sensitivity, negative predictive value, and accuracy at the expense of a reduction in positive predictive value and specificity offered by the sole...

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Published in:Multiple sclerosis and related disorders 2023-11, Vol.79, p.104997-104997, Article 104997
Main Authors: Tortosa-Carreres, Jordi, Quiroga-Varela, Anna, Castillo-Villalba, Jessica, Piqueras-Rodríguez, Mónica, Ramió-Torrenta, Lluís, Cubas-Núñez, Laura, Gasqué-Rubio, Raquel, Quintanilla-Bordas, Carlos, Huertas-Pons, Joana María, Miguela, Albert, Casanova, Bonaventura, Laiz-Marro, Begoña, Pérez-Miralles, Francisco Carlos
Format: Article
Language:English
Subjects:
Diagnosis
Free kappa light chains
Intrathecal synthesis
Multiple sclerosis
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Summary:•The combined use of certain algorithms involving index of free kappa light chains along with oligoclonal IgG bands and other calculations can increase sensitivity, negative predictive value, and accuracy at the expense of a reduction in positive predictive value and specificity offered by the sole use of these parameters.•Through the use of these algorithms, the consumption of oligoclonal bands can be minimized without losing the ability to predict intrathecal synthesis.•An algorithm named KRO, based on determining the index of free kappa light chains initially, followed by the reiber formula with oligoclonal bands reserved for borderline index of free kappa light chains values resulting negative in the reiber formula, was the one that achieved higher sensitivity and accuracy in detecting intrathecal IgG synthesis. This came at the expense of losing some sensitivity and a slight decrease in positive predictive value.•By using a combination of free kappa light chains and oligoclonal bands, it is possible to compensate for the inherent limitations of each individual technique.•According to the KRO algorithm, the usage of oligoclonal bands can be reduced by 91%. Furthermore, they can be employed when seeking information about IgG clonality or determining the intrathecally synthesized immunoglobulin isotype. Intrathecal immunoglobulin synthesis (ITS) plays a crucial role in the diagnosis of multiple sclerosis (MS). Traditionally, the gold standard method for detecting ITS has been through the analysis of oligoclonal bands (OCB). However, the paradigm has shifted with the introduction of the free kappa light chains (FKLC) method. In fact, a recent consensus recommends evaluating FKLC index (FKLCi) as the primary approach and reserving oligoclonal bands with borderline results. The objective of our study is to investigate the diagnostic efficiency of combining FKLC with other methods to predict ITS while minimizing the reliance on OCB. A total of 192 patients were included in the study, consisting of 145 individuals diagnosed with multiple sclerosis (pwMS) and 46 with other neurological diseases (controls). Among the MS cases, 100 patients were assigned to the Training Cohort (TC), while an external Validation Cohort (VC) comprised of 45 MS patients was established. Diagnostic efficiency was assessed for FKLCi, OCB, Link index, and the Reiber formula for IgG and FKLC. Optimal cutoff values for Link index and FKLCi were also determined. The last procedure was de
ISSN:2211-0348
2211-0356
DOI:10.1016/j.msard.2023.104997