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Review
. 2024 May 9;25(10):5170.
doi: 10.3390/ijms25105170.

Laboratory Diagnosis of Intrathecal Synthesis of Immunoglobulins: A Review about the Contribution of OCBs and K-index

Maria Morello  1   2   3 , Simone Mastrogiovanni  1   2 , Fabio Falcione  1   2 , Vanessa Rossi  1   2 , Sergio Bernardini  1   2   3 , Stefania Casciani  1 , Antonietta Viola  1 , Marilina Reali  1 , Massimo Pieri  1   2   3
Affiliations
Review

Laboratory Diagnosis of Intrathecal Synthesis of Immunoglobulins: A Review about the Contribution of OCBs and K-index

Maria Morello et al. Int J Mol Sci. .

Abstract

The diagnosis of MS relies on a combination of imaging, clinical examinations, and biological analyses, including blood and cerebrospinal fluid (CSF) assessments. G-Oligoclonal bands (OCBs) are considered a "gold standard" for MS diagnosis due to their high sensitivity and specificity. Recent advancements have involved the introduced of kappa free light chain (k-FLC) assay into cerebrospinal fluid (CSF) and serum (S), along with the albumin quotient, leading to the development of a novel biomarker known as the "K-index" or "k-FLC index". The use of the K-index has been recommended to decrease costs, increase laboratory efficiency, and to skip potential subjective operator-dependent risk that could happen during the identification of OCBs profiles. This review aims to provide a comprehensive overview and analysis of recent scientific articles, focusing on updated methods for MS diagnosis with an emphasis on the utility of the K-index. Numerous studies indicate that the K-index demonstrates high sensitivity and specificity, often comparable to or surpassing the diagnostic accuracy of OCBs evaluation. The integration of the measure of the K-index with OCBs assessment emerges as a more precise method for MS diagnosis. This combined approach not only enhances diagnostic accuracy, but also offers a more efficient and cost-effective alternative.

Keywords: CSF indexes k-FLC; K-index; free light chains; multiple sclerosis diagnosis; nephelometry and turbidimetry; neurodegeneration; oligoclonal bands.

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Conflict of interest statement

The authors declare no conflicts of interest, except for Laura Ioannilli, who acts as a medical scientific liaison for the Science Department at Binding Site, part of Thermo Fisher Scientific.

Figures

Figure 1
Figure 1
Range cut-off K-index used to discriminate MS-positive patients from controls. A total of 72% of papers reported a value of K-index cut-off between 2.4 and 7.83; 21% of papers used a cut-off between 8.33 and 9.58. Only a few studies (7%) measured a cut-off K-index range between 10.62 and 12.3%.
Figure 2
Figure 2
Techniques used for KFLC measurement. The Freelite analyzer method was used and reported in 63.33% of papers. The N-Latex method was reported in 40%. The Freelite analyzer offers a minimum K-index cut-off value of 5.9 (with sensitivity and specificity of 93% and 95%, respectively).
Figure 3
Figure 3
MS diagnosis: the common flowchart used in a laboratory. Both the K-index and isoelectrofocusing technique (IEF) are performed to characterize/confirm the presence of OCBs.
See this image and copyright information in PMC

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