Kappa Free Light Chain Index Predicts Disease Course in Clinically and Radiologically Isolated Syndromes

Abstract

Background and objectives: To evaluate whether the kappa free light chain index (K-index) can predict the occurrence of new T2-weighted MRI lesions (T2L) and clinical events in clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS).

Methods: All consecutive patients presenting for the diagnostic workup, including CSF analysis, of clinical and/or MRI suspicion of multiple sclerosis (MS) since May 1, 2018, were evaluated. All patients diagnosed with CIS and RIS with at least 1-year follow-up were included. Clinical events and new T2L were collected during follow-up. The K-index performances in predicting new T2L and a clinical event were evaluated using time-dependent ROC analyses. The time to clinical event or new T2L was estimated using survival analysis according to the binarized K-index using an independent cutoff of 8.9, and the ability of each variable to predict outcomes was compared using the Harrell c-index.

Results: One hundred and eighty two patients (146 CIS and 36 RIS, median age 39 [30; 48] y-o, 70% females) were included with a median follow-up of 21 [13, 33] months. One hundred five (58%) patients (85 CIS and 20 RIS) experienced new T2L, and 28 (15%; 21 CIS and 7 RIS) experienced a clinical event. The K-index could predict new T2L over time in CIS (area under the curve [AUC] ranging from 0.86 to 0.96) and in RIS (AUC ranging from 0.84 to 0.54) but also a clinical event in CIS (AUC ranging from 0.75 to 0.87). Compared with oligoclonal bands (OCBs), the K-index had a better sensitivity and a slight lower specificity in predicting new T2L and clinical events in both populations. In the predictive model, the K-index was the variable that best predict new T2L in both CIS and RIS but also clinical events in CIS (c-index ranging from 0.70 to 0.77), better than the other variables, including OCB.

Discussion: This study provides evidence that the K-index predicts new T2L in CIS and RIS but also clinical attack in patients with CIS. We suggest adding the K-index in the further MS diagnosis criteria revisions as a dissemination-in-time biomarker.

Figure 1. Time-Dependent ROC Analyses

The figure shows the ability of the K-index to predict over time (time-dependent AUC) new T2L occurrence in patients with CIS (panel A), new T2L occurrence in people with RIS (panel B), and clinical event occurrence in patients with CIS (panel C). Overall, the ability of the K-index to predict outcomes increases over time for CIS but decreases for RIS. The dashed lines show time-dependent CIs. AUC = area under the curve; CIS = clinically isolated syndrome; RIS = radiologically isolated syndrome; T2L = T2-weighted MRI lesions.

Figure 2. Survival Analysis Evaluating New T2L Occurrence in Patients With CIS According to Their Binary K-Index and OCB Status

The figure shows the time to new T2L in patients with CIS according to their positive (blue line) or negative (red line) K-index status (panel A) and their positive (blue line) or negative (red line) OCB status (panel B). OCB = oligoclonal band; T2L = T2-weighted MRI lesions.

Figure 3. Survival Analysis Evaluating Clinical Attack Occurrence in Patients With CIS According to Their Binary K-Index and OCB Status

The figure shows the time to clinical attack occurrence in patients with CIS according to their positive (blue line) or negative (red line) K-index status (panel A) and their positive (blue line) or negative (red line) OCB status (panel B). CIS = clinically isolated syndrome; OCB = oligoclonal band.