The heterogeneity of multiple sclerosis (MS) makes prognosis and prediction of progression to disability problematic. However, research has now found that the ratio of different classes of immunoglobulin light chain in the cerebrospinal fluid (CSF) predicts progression to disability in patients with MS. The researchers detected an increased ratio of immunoglobulin κ:λ free light chains in the CSF of patients with MS compared with controls, and a high ratio was associated with a low Expanded Disability Status Scale score at follow-up 5 years after the diagnostic lumbar puncture. The change in immunoglobulin ratio resulted from the selective expansion of CSF plasmablasts expressing the κ class of immunoglobulin light chain. The κ:λ free light chain ratio could represent a useful early predictor of disability and facilitate the stratification of patients with MS in clinical trials.