PT  - JOURNAL ARTICLE
AU  - Emma Rathbone
AU  - Lindsay Durant
AU  - James Kinsella
AU  - Antony R Parker
AU  - Ghaniah Hassan-Smith
AU  - Michael R Douglas
AU  - S John Curnow
TI  - Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis
AID  - 10.1136/jnnp-2018-317947
DP  - 2018 May 14
TA  - Journal of Neurology, Neurosurgery & Psychiatry
PG  - jnnp-2018-317947
4099  - http://jnnp.bmj.com/content/early/2018/05/14/jnnp-2018-317947.short
4100  - http://jnnp.bmj.com/content/early/2018/05/14/jnnp-2018-317947.full
AB  - Objective To determine whether the ratio of cerebrospinal fluid (CSF) immunoglobulin kappa to lambda light chains at time of multiple sclerosis (MS) diagnosis predicts disease progression and whether this was intrinsic to CSF plasmablasts.Methods CSF and peripheral blood were obtained from patients undergoing elective diagnostic lumbar puncture and included clinically isolated syndrome (CIS) (n=43), relapsing remitting MS (RRMS; n=50), primary progressive MS (PPMS; n=20) and other neurological disease controls, both inflammatory (ONID; n=23) and non-inflammatory (OND; n=114). CSF samples were assayed for free and immunoglobulin-associated light chains and on B cells and plasmablasts. Clinical follow-up data were collected during a 5-year follow-up period where available.Results There was an increased median CSF κ:λ free light chain (FLC) in all MS groups (CIS: 18.2, 95% CI 6.8 to 30.3; RRMS: 4.4, 95% CI 2.7 to 11.4; PPMS: 12.0, 95% CI 3.6 to 37.1) but not controls (OND: 1.61, 95% CI 1.4 to 1.9; ONID: 1.7, 95% CI 1.3 to 2.2; p<0.001). This ratio predicted Expanded Disability Status Scores (EDSS) progression at 5 years, with a lower median EDSS in the group with high (>10) CSF κ:λ FLC (0.0, 95% CI 0 to 2.5 vs 2.5, 95% CI 0 to 4, high vs low; p=0.049). CSF κ:λ FLC correlated with CSF IgG1 κ:λ (r=0.776; p<0.0001) and was intrinsic to CSF plasmablasts (r=0.65; p=0.026).Conclusions These data demonstrate that CSF immunoglobulin κ:λ ratios, determined at the time of diagnostic lumbar puncture, predict MS disease progression and may therefore be useful prognostic markers for early therapeutic stratification.