Higher cerebrospinal fluid (CSF) kappa free light chain (KFLC) index was associated with reduced white matter myelin content and greater disability in individuals with early relapsing-remitting multiple sclerosis (RRMS), according to findings presented at the 2026 Joint ACTRIMS-ECTRIMS Meeting (MS Toronto 2026). The prospective study identified associations between KFLC index, quantitative MRI measures of myelin integrity, and clinical disability, providing additional insight into the potential relevance of this biomarker beyond MS diagnosis.

The study included 131 participants with early RRMS who underwent baseline CSF KFLC index measurement and longitudinal quantitative MRI assessments at baseline and annually for 60 months. Investigators evaluated myelin content in normal-appearing white matter (NAWM), MS lesions, cortical and deep grey matter, and global brain measures. Linear mixed-effects models assessed associations between baseline KFLC index and imaging outcomes, adjusting for age, sex, disease duration, Expanded Disability Status Scale (EDSS) score, and treatment. Mediation analyses examined whether myelin content could explain the relationship between KFLC index and disability.

Key findings from the study include the following:

  • Normal-appearing white matter: Higher KFLC index was associated with lower myelin content (β=−0.72; P<.001).
  • MS lesions: Higher KFLC index was also associated with reduced lesion myelin content (β=−0.80; P=.006).
  • Grey matter findings: No associations were observed for global or cortical grey matter measures, although a positive association was identified in deep grey matter (β=0.20; P=.03).
  • Longitudinal changes: Significant KFLC-by-time interactions were observed for myelin content in NAWM (P=.017) and lesions (P=.025), indicating that differences associated with baseline KFLC index diminished during follow-up.
  • Disability associations: Lower myelin content was associated with higher EDSS scores. The association between KFLC index and disability weakened after adjustment for myelin content, consistent with a potential mediating relationship.

The findings suggest that KFLC index, which has been incorporated into the 2024 McDonald diagnostic criteria, may also reflect aspects of white matter tissue integrity in early MS. Investigators proposed that myelin damage could help explain the association between intrathecal inflammation and clinical disability.

Source: Rosenstein I, Hartnor M, Johnsson M. Kappa free light chain index is associated with reduced myelin content and predicts myelin loss in white matter and lesions in relapsing-remitting multiple sclerosis. Abstract 482. Presented at: 10th Joint ACTRIMS-ECTRIMS Meeting (MS Toronto 2026); October 21–23, 2026; Toronto, Canada.