Free light chains analysis in cerebrospinal fluid for the diagnosis of multiple sclerosis: A study in the Israeli population

Abstract

Background

The 2024 revision of the McDonald criteria for multiple sclerosis (MS) recognized kappa free light chain (FLCκ) as a quantitative biomarker of intrathecal immunoglobulin synthesis equivalent to oligoclonal bands (OCB). However, diagnostic performance of reported FLC thresholds vary across laboratories due to differences in instrumentation, assay type, population and regional characteristics.

Objectives

Assessing of the utility of nephelometric FLC assay for MS diagnosis in an Israeli cohort.

Methods

A total of 135 patients with MS, non-MS demyelinating/inflammatory and non-demyelinating neurological disorders were tested using FLC assay and OCB technique. FLCκ and λ concentration and their index values were estimated. Statistical analysis methods included Mann-Whitney and Kruskal-Wallis tests, Spearman correlation, and receiver operating characteristic (ROC) curves.

Results

FLCκ metrics outperformed FLCλ in diagnosing MS. Using FLCκ index, a threshold 7.0 yielded 82% specificity and 77.1% sensitivity, while 72% specificity and 82% sensitivity was achieved using κ concentration cut-off 0.19 mg/L. Specificity of OCB test (84%) was similar to that of FLCκ index, though OCB sensitivity (88.6%) exceeded the FLC-based metrics. Specifically, cases with κ index >11 and concentration > 0.2 mg/L were MS or OCB-positive, whereas cases with κ concentration < 0.1 mg/L were non-MS or OCB-negative. Hence, 60% of the cases may be safely excluded from OCB testing.

Conclusions

Optimized FLCκ thresholds effectively assist MS diagnosis within Israeli population. Combined FLC thresholds (κ index and concentration values) were established for screening clearly defined/unequivocal cases that may not require time-consuming operator-dependent OCB analysis. Rapid quantitative FLC assay holds promise as a screening tool for unequivocal cases prior to OCB testing.