Kappa-Free Light Chains in CSF Predict Early Multiple Sclerosis Disease Activity

Abstract

Objective: To investigate whether κ-free light chain (κ-FLC) index predicts multiple sclerosis (MS) disease activity independent of demographics, clinical characteristics, and MRI findings.

Methods: Patients with early MS who had CSF and serum sampling at disease onset were followed for 4 years. At baseline, age, sex, type of symptoms, corticosteroid treatment, and number of T2 hyperintense (T2L) and contrast-enhancing T1 lesions (CELs) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying therapy (DMT) were registered. κ-FLCs were measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient.

Results: A total of 88 patients at a mean age of 33 ± 10 years and female predominance of 68% were included; 38 (43%) patients experienced a second clinical attack during follow-up. In multivariate Cox regression analysis adjusting for age, sex, T2L, CEL, disease and follow-up duration, administration of corticosteroids at baseline and DMT during follow-up revealed that κ-FLC index predicts time to second clinical attack. Patients with κ-FLC index >100 (median value 147) at baseline had a twice as high probability for a second clinical attack within 12 months than patients with low κ-FLC index (median 28); within 24 months, the chance in patients with high κ-FLC index was 4 times as high as in patients with low κ-FLC index. The median time to second attack was 11 months in patients with high κ-FLC index whereas 36 months in those with low κ-FLC index.

Conclusion: High κ-FLC index predicts early MS disease activity.

Classification of evidence: This study provides Class II evidence that in patients with early MS, high κ-FLC index is an independent risk factor for early second clinical attack.

Figure 1. Increased κ-FLC Index in Patients Who Convert to CDMS

κ-FLC = κ-free light chain; CDMS = clinically definite multiple sclerosis.

Figure 2. Probability of Clinically Definite Multiple Sclerosis Over 4 Years

The probability of development of a second clinical attack, i.e., conversion to CDMS, during the 4-year follow-up period was higher in the high κ-FLC index (>100) group (n = 19) than in the low κ-FLC index (≤100) group (n = 69; p = 0.009). κ-FLC = κ-free light chain; CDMS = clinically definite multiple sclerosis.