Cerebrospinal fluid free kappa light chains and kappa index perform equal to oligoclonal bands in the diagnosis of multiple sclerosis

AbstractBackgroundDetection of intrathecal immunoglobulin G (IgG) synthesis by gold standard oligoclonal bands (OCB) or IgG index remains an integral part of multiple sclerosis (MS) diagnostics, although both methods have weaknesses. Emerging evidence suggests that automated detection of free light chains (FLC) in the cerebrospinal fluid (CSF) has diagnostic performance equal to OCB. The objective of this study was to compare the diagnostic performance of CSF FLC with OCB and IgG index in a large cohort of Scandinavian patients referred for MS evaluation.MethodsWe prospectively included 230 patients suspected for MS. They are composed of patients with MS (n=96), clinically isolated syndrome (n=37), other neurological diseases (OND, n=31) and symptomatic controls (SC, n=66). CSF and serum samples were analyzed for kappa and lambda FLC, OCB and IgG index. Diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis.ResultsBoth the absolute concentration of CSF-kappa and the kappa index had excellent MS diagnostic performances with ROC area under the curve of 0.93 and 0.94 (MS vs. SC+OND). At the 0.42 mg/L cutoff, CSF-kappa had sensitivity and specificity of 93.8% and 85.6%, whereas sensitivity and specificity for OCB was 82.3% and 93.8% (72.9% and 95.9% for IgG index at cutoff 0.64). CSF-lambda and lambda index performed inferior to CSF-kappa and kappa index.ConclusionsCSF-kappa and kappa index represent automated, rapid and low-cost alternatives to OCB. Using merely the absolute concentration of CSF-kappa is a logistic advantage in the clinical laboratories.

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Effects of natalizumab on oligoclonal bands in the cerebrospinal fluid of multiple sclerosis patients: A longitudinal study

Multiple Sclerosis Journal ◽

10.1177/1352458514538111 ◽

2014 ◽

Vol 20 (14) ◽

pp. 1900-1903 ◽

Cited By ~ 27

Author(s):

R Mancuso ◽

D Franciotta ◽

M Rovaris ◽

D Caputo ◽

A Sala ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Longitudinal Study ◽

Retrospective Studies ◽

Oligoclonal Bands ◽

Igg Index ◽

Before And After ◽

Oligoclonal Igg ◽

Multiple Sclerosis Patients

Retrospective studies show that natalizumab modifies oligoclonal immunoglobulin (IgG) bands (OCBs) in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. In this study, we prospectively analyzed both serum and CSF samples from 24 MS patients, before and after 2 years of natalizumab-based therapy. Our results showed complete (55%) or partial (27%) disappearance of the OCBs in CSF samples that were taken after 2 years of therapy. Intrathecal IgG production, represented by the IgG index and IgGLoc, was also quantitatively reduced. Our data showed that natalizumab substantially modulates both intrathecal polyclonal and oligoclonal IgG production: This effect was much more potent than was previously reported.

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CORRELATION OF THE IGG INDEX AND OLIGOCLONAL BANDS IN THE CEREBROSPINAL FLUID OF PATIENTS WITH MULTIPLE SCLEROSIS

Biomedical Papers ◽

10.5507/bp.2008.038 ◽

2008 ◽

Vol 152 (2) ◽

pp. 247-249 ◽

Cited By ~ 11

Author(s):

Jan Mares ◽

Roman Herzig ◽

Karel Urbanek ◽

Vladimira Sladkova ◽

Jaroslava Sklenarova ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Oligoclonal Bands ◽

Igg Index

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Sensitivity and specificity of cerebrospinal fluid free light chains in Argentinean patients with suspected multiple sclerosis

10.26226/morressier.59a3eda9d462b8028d894073 ◽

2017 ◽

Author(s):

María S. Sáez

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Sensitivity And Specificity ◽

Light Chains ◽

Free Light Chains

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Oligoclonal Bands in Cerebrospinal Fluid of Black Patients with Multiple Sclerosis

BioMed Research International ◽

10.1155/2015/217961 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Paulo Diniz da Gama ◽

Luís dos Ramos Machado ◽

José Antonio Livramento ◽

Hélio Rodrigues Gomes ◽

Tarso Adoni ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Ethnic Differences ◽

Statistical Significance ◽

Oligoclonal Bands ◽

Mixed Group ◽

Black Patients ◽

Igg Index ◽

The City ◽

Lower Statistical Significance

Genetic susceptibility is a well-recognized factor in the onset of multiple sclerosis (MS). The objective of this study was to determine the frequency of oligoclonal bands (OCB) restricted to the cerebrospinal fluid, in an ethnically mixed group of MS patients in the city of São Paulo, Brazil. Techniques used to detect OCB consisted of isoelectric focusing followed by immunoblotting. OCB were found in 49 (54.4%) out of 90 patients with clinically definite MS; out of the 23 brown/black patients, 17 (73.9%) were OCB+; out of the 66 white patients, 32 (48.5%) were OCB+; and the only patient yellow was OCB+ (p=0.05). Analysis of the IgG index was also consistent with the findings, but with lower statistical significance. The data presented in our study show that the ethnic differences in MS extend to the immune response.

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Multiple sclerosis: assay of free immunoglobulin light chains

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563216652175 ◽

2016 ◽

Vol 54 (1) ◽

pp. 5-13 ◽

Cited By ~ 14

Author(s):

DB Ramsden

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Clinical Characteristics ◽

Historical Context ◽

Oligoclonal Bands ◽

Light Chains ◽

Immunoglobulin Light Chains ◽

Future Developments ◽

The Past ◽

Qualitative Detection

Over the past five years, a number of papers have appeared describing the assay of free immunoglobulin light chains in cerebrospinal fluid to assist in the diagnosis of multiple sclerosis. The assay of kappa free immunoglobulin chains is being advocated as a technically simpler and cheaper quantitative alternative to the qualitative detection of oligoclonal bands. This article reviews the analytical and clinical characteristics of these immunoglobulin free light chain assays and places them in their historical context and possible future developments.

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Multiple sclerosis: use of light-chain typing to assist diagnosis

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1258/0004563011900669 ◽

2001 ◽

Vol 38 (3) ◽

pp. 235-241 ◽

Cited By ~ 14

Author(s):

Margaret A Jenkins ◽

Louisa Cheng ◽

Sujiva Ratnaike

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Oligoclonal Bands ◽

Light Chains ◽

Banding Patterns ◽

Diagnostic Use ◽

Clinical Laboratories ◽

Oligoclonal Banding ◽

Oligoclonal Igg ◽

Abnormal Ratio

Although the presence of oligoclonal IgG with abnormal ratio in multiple sclerosis (MS) has been known for many years, this finding has not been put to diagnostic use in most routine clinical laboratories. In a retrospective study we report differences in the oligoclonal banding patterns between multiple sclerosis and non-MS patients. We had sufficient cerebrospinal fluid (CSF) on 36 from 71 patients with oligoclonal bands for immunofixation for κ and λ light chains, and for free κ and free λ. Thirteen out of 14 patients with clinically confirmed MS had predominantly IgG (κ) banding. In contrast, in seven out of eight patients with diagnoses other than MS the IgG was linked to both κ and λ light chains in approximately equal proportions. Nine out of 14 patients with probable/possible/ suspected MS showed predominantly IgG (κ) banding; five others in this group had both IgG (κ) and IgG (λ) and free λ light chains. The finding of IgG (κ) bands in CSF samples with oligoclonal bands supports a diagnosis of MS.

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New-Onset Gait Difficulty With Kappa Free Light Chains in Cerebrospinal Fluid

10.1093/med/9780197583425.003.0013 ◽

2021 ◽

pp. 42-43

Author(s):

Maria Alice V. Willrich ◽

Ruba S. Saadeh

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Magnetic Resonance ◽

Oligoclonal Bands ◽

Light Chains ◽

Resonance Imaging ◽

Free Light Chains ◽

Mcdonald Criteria ◽

T2 Hyperintensity

A 49-year-old woman sought care for a 9-month history of gait difficulty. She was dragging her right foot when walking and could not walk more than 3 blocks because of right leg weakness. Physical examination showed right-sided weakness of hip flexion and foot dorsiflexion and symmetrical hyperreflexia at the knees and ankles. Magnetic resonance imaging of the brain showed multiple foci of T2 hyperintensity throughout the white matter in both cerebral and cerebellar hemispheres, predominantly in a periventricular distribution. Several small enhancing lesions and mild generalized cerebral volume loss were seen. The appearance and distribution were consistent with a demyelinating process such as multiple sclerosis. Magnetic resonance imaging of the cervical and thoracic spine showed multiple small T2 hyperintensities, including 1 enhancing lesion in the cervical spinal cord. Oligoclonal bands were positive, with 11 unique bands in the cerebrospinal fluid. The concentration of cerebrospinal fluid kappa free light chains was increased, at 0.314 mg/dL. The patient was diagnosed with relapsing-remitting multiple sclerosis. A 5-day course of intravenous corticosteroids was started, after which she noted clinical improvement. At her last follow-up 2 years after initial evaluation, the patient has been stable with no new clinical multiple sclerosis episodes and stable magnetic resonance imaging disease burden with no new lesions. The diagnosis of multiple sclerosis incorporates clinical, imaging, and laboratory evidence. The 2017 revised McDonald criteria state that a finding of cerebrospinal fluid -specific oligoclonal bands can replace the criterion for dissemination in time to make a diagnosis of definitive multiple sclerosis. The standard test for oligoclonal bands is performed using isoelectric focusing electrophoresis and takes more than 3 hours to complete. The case patient had 11 unique cerebrospinal fluid bands. The number of bands is not correlated with disease severity or prognosis.

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Application of κ free light chains in cerebrospinal fluid as a biomarker in multiple sclerosis diagnosis: development of a diagnosis algorithm

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0285 ◽

2018 ◽

Vol 56 (4) ◽

pp. 609-613 ◽

Cited By ~ 13

Author(s):

Estefania Valencia-Vera ◽

Ana Martinez-Escribano Garcia-Ripoll ◽

Alfredo Enguix ◽

Carmen Abalos-Garcia ◽

Maria Jesus Segovia-Cuevas

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

High Sensitivity ◽

Demyelinating Diseases ◽

Oligoclonal Bands ◽

Light Chains ◽

Moderate Increase ◽

Free Light Chains ◽

Cross Sectional ◽

Significant Difference

Abstract Background: The determination of κ free light chains (KFLC) in cerebrospinal fluid (CSF) by nephelometry is a feasible alternative to immunoglobulin G oligoclonal bands (OCB) in the evaluation of intrathecal synthesis of immunoglobulin in multiple sclerosis (MS) and other demyelinating diseases. The aim of this study was to assess the diagnostic value of KFLC and its inclusion in a procedure algorithm along with OCB interpretation. Methods: A cross-sectional study, which included 123 patients with a CSF OCB request, was carried out. Isoelectric focusing followed by immunofixation was used to detect OCB, and nephelometry was used to analyze KFLC. The KFLC index was calculated using CSF/serum quotient of KFLC and albumin. The KFLC index was compared with MS diagnosis to find the optimal cutoff. It was obtained from the receiver operating characteristic (ROC) curves and the Youden method. Results: The CSF KFLC median was 1.66 mg/L in the MS group, whereas in other central nervous system diseases, KFLC showed generally no or only moderate increase in CSF (median 0.10 mg/L). KFLC index showed a significant difference between groups. ROC analysis for CSF KFLC concentration, and KFLC indexes were 91.88% and 93.94%, respectively. The best cutoff for the KFLC index was 2.91 for MS diagnosis (sensitivity: 83.78%; specificity: 85.88%). The proposed algorithm showed high sensitivity (89.19%) and specificity (84.71%). Conclusions: KFLC determination is rapid and automatized, but it has no higher sensitivity and specificity than OCB in MS diagnosis. Nevertheless, when used in screening, it could reduce the number of manual OCB tests.

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