Highlights
- •Oligoclonal banding is currently the gold standard to demonstrate intrathecal IgG synthesis.
- •CSF kappa quantification has similar sensitivity as oligoclonal banding to detect multiple sclerosis.
- •CSF kappa testing can be performed as a screening test for intrathecal IgG synthesis in suspected multiple sclerosis, which, if positive, can be confirmed by oligoclonal banding.
Abstract
Background
CSF free light chains help diagnose multiple sclerosis, but no data is available on
the Asian population. Our objective was to study the diagnostic utility of CSF free
light chains for diagnosing multiple sclerosis in Indian patients.
Methods
Prospective multicentric case-control study. Cases included those who were tested
for oligoclonal bands and fulfilled the modified McDonald criteria 2017 for multiple
sclerosis and clinically isolated syndromes. Those tested for oligoclonal bands (OCB)
but with other diagnoses- inflammatory and non-inflammatory were included as controls.
Clinical details were collected from electronic medical records. CSF and serum kappa
and lambda free light chains were measured, apart from oligoclonal bands, immunoglobulin,
and albumin in paired serum and CSF samples.
Results
There were 70 patients (31 cases and 39 controls). The mean age was 43.41(SD 16.073)
years, and 43(61.4%) were females. CSF kappa showed highest specificity 97.4%, at
a cut off 2.06 mg/L (sensitivity 71%) and highest sensitivity 90.3%, at a cut off
0.47 mg/L (specificity 79.5%). Best balance of sensitivity and specificity for CSF
kappa was seen at a cut-off of ≥ 0.63 mg/L {sensitivity 87·1 (CI - 70.17–96.37), and
specificity 87·18 (CI -72.57–95.70)}. The ratio of Kappa/lambda showed highest specificity
of 100%(similar to OCB) with a sensitivity of 71% at a cut off of 1.72. The ratio
of sum of kappa and lambda light chains, and Qalb (∑CSF FLC/Qalb), showed the highest
specificity (94.87%)among the blood brain barrier corrected ratios.
Conclusion
This study showed that the diagnostic utility of CSF kappa was comparable to OCB to
diagnose multiple sclerosis in sensitivity, but not specificity, so can be a screening
test before testing for OCB in our population.
Keywords
Abbreviations:
CIS (clinical isolated syndrome), CSF (Cerebrospinal fluid), KFLC (Kappa free light chains), LFLC (Lambda free light chains), OCB (Oligoclonal banding)To read this article in full you will need to make a payment
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References
- CSF isoelectrofocusing in a large cohort of MS and other neurological diseases.Eur. J. Neurol. 2004; 11: 525-529https://doi.org/10.1111/j.1468-1331.2004.00822.x
- Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude.J. NeurolNeurosurg. Psychiatry. 2013; 84: 909-914https://doi.org/10.1136/jnnp-2012-304695
- Determination of kFLC and K index in cerebrospinal fluid: a valid alternative to assess intrathecal immunoglobulin synthesis.J. Neuroimmunol. 2013; 263: 116-120
- Cerebrospinal fluid oligoclonal bands in the diagnosis of multiple sclerosis: isoelectric focusing with IgG immunoblotting compared with high-resolution agarose gel electrophoresis and cerebrospinal fluid IgG index.Am. J. Clin. Pathol. 2003; 120: 672-675
- Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement: a consensus statement.Arch. Neurol. 2005; 62: 865-870https://doi.org/10.1001/archneur.62.6.865
- The role of B cells in the immunopathogenesis of multiple sclerosis.Immunology. 2020; 160: 325-335https://doi.org/10.1111/imm.13198
- Kappa free light chains and IgG combined in a novel algorithm for the detection of multiple sclerosis.Brain Sci. 2020; 10: 324https://doi.org/10.3390/brainsci10060324
- CSF free light chain identification of demyelinating disease: comparison with oligoclonal banding and other CSF indexes.Clin. Chem. Lab. Med. 2018; 56: 1071-1080https://doi.org/10.1515/cclm-2017-0901
- High sensitivity and specificity of elevated cerebrospinal fluid kappa free light chains in suspected multiple sclerosis.J. Neuroimmunol. 2014; 276: 175-179https://doi.org/10.1016/j.jneuroim.2014.08.003
- Guidelines for CSF processing and biobanking: impact on the identification and development of optimal CSF protein biomarkers.Methods Mol. Biol. 2019; 2044: 27-50https://doi.org/10.1007/978-1-4939-9706-0_2
- A pathogenic role for myelin-specific Cd8+ T cells in a model for multiple sclerosis.J. Exp. Med. 2001; 194: 669-676https://doi.org/10.1084/jem.194.5.669
- Free light chains and intrathecal B cells activity in multiple sclerosis: a prospective study and meta-analysis.Mult. Scler. Int. 2016; 2016 (Epub 2016 Dec 28): 2303857https://doi.org/10.1155/2016/2303857
- Validation of kappa free light chains as a diagnostic biomarker in multiple sclerosis and clinically isolated syndrome: a multicenter study.Mult. Scler. 2016; 22: 502-510https://doi.org/10.1177/1352458515594044
- Diagnostic relevance of free light chains in cerebrospinal fluid–the hyperbolic reference range for reliable data interpretation in quotient diagrams.Clin. Chim. Acta. 2019; 497 (Oct 1): 153-162
- CSF kappa free light chains: cutoff validation for diagnosing multiple sclerosis.Mayo Clin. Proc. 2022; 97: 738-751https://doi.org/10.1016/j.mayocp.2021.09.014
- Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria.Lancet Neurol. 2018; 17: 162-173https://doi.org/10.1016/s1474-4422(17)30470-2
- Intrathecal kappa free light chains as markers for multiple sclerosis.Sci. Rep. 2020; 10: 20329https://doi.org/10.1038/s41598-020-77029-7
- A study of oligoclonal band negative multiple sclerosis.J. NeurolNeurosurg. Psychiatry. 1996; 60: 27-30https://doi.org/10.1136/jnnp.60.1.27
- A guide to the interpretation of CSF indices.Lab. Med. 2005; 36: 558-562https://doi.org/10.1309/0d1f-gl7a-jxe3-vqby
Article info
Publication history
Published online: April 11, 2023
Accepted:
April 10,
2023
Received in revised form:
April 6,
2023
Received:
August 10,
2022
Identification
Copyright
© 2023 Elsevier B.V. All rights reserved.
