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CSF immunoglobulin ratio predicts MS progression

A study led by the University of Birmingham has found that the ratio of cerebrospinal fluid (CSF) immunoglobulin kappa to lambda (κ:λ) light chains at time of diagnosis predicts disease progression in multiple sclerosis (MS).

The research, published in the Journal of Neurology, Neurosurgery & Psychiatry, analysed free (FLC) and immunoglobulin-associated light chains and on B cells and plasmablasts from patients with clinically isolated syndrome (CIS; n=43), relapsing remitting MS (RRMS; n=50), primary progressive MS (PPMS; n=20) and other neurological disease (OND) controls, both inflammatory (other neurological inflammatory disease [ONID]; n=23) and noninflammatory (OND; n=114). Clinical follow-up data were collected during a 5-year follow-up period where available.

Median CSF κ:λ FLC was found to be increased in all MS groups compared with control groups. κ:λ FLC was 18.2 in CIS (95% CI, 6.8-30.3), 4.4 in RRMS (95% CI, 2.7-11.4) and 12.0 in PPMS  (95% CI, 3.6-37.1) compared with 1.61 in OND (95% CI, 1.4-1.9) and 1.7 in ONID (95% CI, 1.3-2.2) (P<.001).

The ratio predicted Expanded Disability Status Scores (EDSS) progression at 5 years, with a lower median EDSS in the group with high (>10) vs low CSF κ:λ FLC (P=.049). CSF κ:λ FLC correlated with CSF IgG1 κ:λ (r, 0.776; P<.0001) and was intrinsic to CSF plasmablasts (r, 0.65; P=.026).

Joint lead author Dr John Curnow of the University of Birmingham's Institute of Inflammation and Ageing said that the findings suggest CSF κ:λ FLC could be a relatively simple test used at diagnosis to help identify patients with a poor prognosis.

"This will enable clinicians to justify the use of highly effective therapies, which could potentially improve the long-term outcomes for these patients,” he said.


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