Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis

Emma Rathbone, Lindsay Durant, James Kinsella, Antony R Parker, Ghaniah Hassan-Smith, Michael R. Douglas, S. John Curnow

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
JournalJournal of Neurology, Neurosurgery and Psychiatry
Early online date9 May 2018
DOIs
Publication statusE-pub ahead of print - 9 May 2018

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Immunoglobulin Light Chains
Multiple Sclerosis
Cerebrospinal Fluid
Disease Progression
Light
Spinal Puncture
Immunoglobulins
Chronic Progressive Multiple Sclerosis
Relapsing-Remitting Multiple Sclerosis
B-Lymphocytes
Immunoglobulin G

Cite this

Rathbone, Emma ; Durant, Lindsay ; Kinsella, James ; Parker, Antony R ; Hassan-Smith, Ghaniah ; Douglas, Michael R. ; Curnow, S. John. / Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis. In: Journal of Neurology, Neurosurgery and Psychiatry. 2018.
@article{f042b3e0e532490cbc49d0dc7ec7bda4,
title = "Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis",
abstract = "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.",
author = "Emma Rathbone and Lindsay Durant and James Kinsella and Parker, {Antony R} and Ghaniah Hassan-Smith and Douglas, {Michael R.} and Curnow, {S. John}",
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Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis. / Rathbone, Emma; Durant, Lindsay; Kinsella, James; Parker, Antony R; Hassan-Smith, Ghaniah; Douglas, Michael R.; Curnow, S. John.

In: Journal of Neurology, Neurosurgery and Psychiatry, 09.05.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis

AU - Rathbone, Emma

AU - Durant, Lindsay

AU - Kinsella, James

AU - Parker, Antony R

AU - Hassan-Smith, Ghaniah

AU - Douglas, Michael R.

AU - Curnow, S. John

PY - 2018/5/9

Y1 - 2018/5/9

N2 - 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.

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.

UR - http://jnnp.bmj.com/content/early/2018/05/14/jnnp-2018-317947

U2 - 10.1136/jnnp-2018-317947

DO - 10.1136/jnnp-2018-317947

M3 - Article

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

SN - 0022-3050

ER -