KFLC to Total CSF Protein Ratio Is an Alternative to KFLC Index to Diagnose Multiple Sclerosis: A Retrospective Study...

Biological analyses are crucial for diagnosing multiple sclerosis (MS), notably detection of oligoclonal bands (OCBs) of immunoglobulin G in CSF. Kappa free light chain (KFLC) quantification in serum and CSF has recently been proposed as an additional test. In a rational medicoeconomic approach, identifying algorithms or biomarkers is important. The objective of this study was, therefore, to evaluate the correlation between CSF kappa free light chain (KFLC_CSF)/total CSF protein ratio (KFLC_CSF/Prot_CSF) and OCB status and its performance in diagnosing MS.

KFLC measurements were performed prospectively with each OCB analysis, and the data were interpreted retrospectively. A total of 814 clinical cases were included: 153 with MS or clinically isolated syndrome (CIS), 181 with other inflammatory neurologic diseases, and 480 with noninflammatory neurologic diseases. Performances of KFLC_CSF/Prot_CSF in predicting OCB status, diagnosing MS, and estimating evolution of CIS to MS were evaluated and compared with those of other KFLC parameters, i.e., KFLC index, and with OCB and IgG parameters.

KFLC_CSF/Prot_CSF and KFLC index performed similarly in predicting OCB status, with a sensitivity of 80.2% and a specificity of 93.4% at a threshold >0.21% for KFLC_CSF/Prot_CSF (area under the curve: 0.93). The percentage of agreement between OCB status and KFLC_CSF/Prot_CSF was 91.2%. Using KFLC_CSF and KFLC_CSF/Prot_CSF initially could reduce OCB testing by 68% and quantitative tests by 48.4%. For diagnosing MS/CIS, KFLC_CSF/Prot_CSF performed similar to or slightly worse than the KFLC index but always outperformed IgG, OCB, and KFLC_CSF. For this indication, the optimal threshold for KFLC_CSF/Prot_CSF was >0.24%. It is important to note that KFLC_CSF/Prot_CSF was the most predictive parameter for CIS progression to MS.

To conclude, KFLC_CSF/Prot_CSF is as an easier and cost-effective alternative for predicting OCB status and CIS progression to MS and assisting in the diagnosis of MS.

This study provides Class II evidence that the KFLC_CSF/Protein_CSF ratio accurately distinguishes patients with CSF OCBs from those without CSF OCBs and patients with MS from those with other neurologic disorders.