Association of CSF Kappa-Free Light Chains With Cortical and Periventricular Brain Damage in Multiple Sclerosis

Kappa-free light chain (κ-FLC) is a quantitative biomarker of intrathecal immunoglobulin synthesis, with diagnostic accuracy comparable to oligoclonal bands in patients with multiple sclerosis (pwMS). However, their association with longitudinal brain MRI parameters remains unclear. We investigated associations between κ-FLC and MRI metrics in pwMS.

In this retrospective cohort study, serum and CSF samples were collected from pwMS with brain MRI performed ≥1 year after lumbar puncture at the Medical University of Graz between 2005 and 2020. κ-FLC concentrations were quantified in paired serum and CSF samples using the Optilite turbidimeter; κ-FLC index was calculated as ratio of the quotient of κ-FLC to albumin. MS lesions were segmented on FLAIR images using the lesion prediction algorithm of SPM's LST toolbox, categorized into periventricular lesions (PVLs) and non-PVLs. We assessed association of κ-FLC with lesion types, hypothesizing their contribution to damage in CSF-proximal regions. Brain volumes (gray, subcortical gray and white matter) and mean cortical thickness were estimated with FreeSurfer v.6.0.

A total of 109 participants were included (66% female, mean age 33.0 ± 9.5 years). Those with κ-FLC index ≥ median showed significantly higher PVL load (median: 3.2 cm³ [interquartile range (IQR) 1.5-8.4]) than those with values below median (median: 1.9 cm³ [IQR 0.9-3.3], p = 0.007). In regression models adjusted for age, sex, follow-up time, baseline corticosteroid use, and disease-modifying therapy, both baseline κ-FLC index and CSF κ-FLC were independently associated with greater total lesion load (κ-FLC index: B = 0.283, 95% CI 0.130-0.436, p < 0.001; CSF κ-FLC: B = 0.255, 95% CI 0.105-0.405, p = 0.001) and PVL load (κ-FLC index: B = 0.286, 95% CI 0.123-0.449, p = 0.001; CSF κ-FLC: B = 0.274, 95% CI 0.115-0.433, p = 0.001) at follow-up. They were also linked to lower mean cortical thickness (κ-FLC index: B = -0.001, 95% CI -0.001-0.0001, p = 0.011; CSF κ-FLC: B = -0.001, 95% CI -0.001-0.0001, p = 0.010).

Higher κ-FLC levels were associated with both PVL burden and cortical pathology, regions adjacent to the CSF. Although this study was limited by a relative small sample size, our findings underscore the potential of κ-FLC as a diagnostic and prognostic MS biomarker.