scholarly journals The Increasing Role of Kappa Free Light Chains in the Diagnosis of Multiple Sclerosis

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3056
Author(s):  
Franz Felix Konen ◽  
Philipp Schwenkenbecher ◽  
Konstantin Fritz Jendretzky ◽  
Stefan Gingele ◽  
Kurt-Wolfram Sühs ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Sensitivity And Specificity ◽  
Diagnostic Sensitivity ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Extensive Literature ◽  
Free Light Chains ◽  
Multicenter Studies ◽  
Non Linear ◽  
Diagnostic Sensitivity And Specificity

Free light chains (FLC) are a promising biomarker to detect intrathecal inflammation in patients with inflammatory central nervous system (CNS) diseases, including multiple sclerosis (MS). The diagnostic use of this biomarker, in particular the kappa isoform of FLC (“KFLC”), has been investigated for more than 40 years. Based on an extensive literature review, we found that an agreement on the correct method for evaluating KFLC concentrations has not yet been reached. KFLC indices with varying cut-off values and blood-CSF-barrier (QAlbumin) related non-linear formulas for KFLC interpretation have been investigated in several studies. All approaches revealed high diagnostic sensitivity and specificity compared with the oligoclonal bands, which are considered the gold standard for the detection of intrathecally synthesized immunoglobulins. Measurement of KFLC is fully automated, rater-independent, and has been shown to be stable against most pre-analytic influencing factors. In conclusion, the determination of KFLC represents a promising diagnostic approach to show intrathecal inflammation in neuroinflammatory diseases. Multicenter studies are needed to show the diagnostic sensitivity and specificity of KFLC in MS by using the latest McDonald criteria and appropriate, as well as standardized, cut-off values for KFLC concentrations, preferably considering non-linear formulas such as Reiber’s diagram.

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

2018 ◽  
Vol 57 (2) ◽  
pp. 210-220 ◽  
Author(s):  
Mikael Christiansen ◽  
Mikkel Carstensen Gjelstrup ◽  
Morten Stilund ◽  
Tove Christensen ◽  
Thor Petersen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Sensitivity And Specificity ◽  
Diagnostic Performance ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Kappa Index ◽  
Absolute Concentration ◽  
Igg Index ◽  
The Absolute

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.

scholarly journals Free Light Chains and Intrathecal B Cells Activity in Multiple Sclerosis: A Prospective Study and Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Gabriella Passerini ◽  
Gloria Dalla Costa ◽  
Francesca Sangalli ◽  
Lucia Moiola ◽  
Bruno Colombo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
Inflammatory Diseases ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
The Other ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Free Light Chains ◽  
A Prospective Study

Background. The presence of CSF oligoclonal bands (OBs) is an independent prognostic factor for multiple sclerosis (MS), but the difficulties in the standardization of the test and the interlaboratory variation in reporting have contributed to its limited use in the diagnosis of the disease. Standard nephelometric assays to measure free light chains (FLC) levels have been recently developed and the test may improve the detection of intrathecal B cells activity.Methods. The presence of OBs, kappa and lambda FLC levels, and standard indices of intrathecal inflammation were assessed in 100 consecutive patients, including patients with MS, clinically isolated syndromes (CIS), other inflammatory diseases of the CNS, and other noninflammatory diseases.Results. Both KFLC and LFLC correlated strongly with the presence of OCBs and with all common tests for intrathecal inflammation (p<0.001for all comparisons). KFLC and LFLC were significantly different in patients with MS and CIS compared to the other groups (p<0.001andp<0.001, resp.) and had a better diagnostic accuracy than all the other tests (area under the curve 82.3 % for KFLC index and 79.3 % for LFLC index).Conclusion. Nephelometric assays for KFLC in CSF reliably detect intrathecal immunoglobulin synthesis and discriminate MS patients.

scholarly journals Kappa Free Light Chains and IgG Combined in a Novel Algorithm for the Detection of Multiple Sclerosis

2020 ◽  
Vol 10 (6) ◽  
pp. 324
Author(s):  
Monika Gudowska-Sawczuk ◽  
Joanna Tarasiuk ◽  
Alina Kułakowska ◽  
Jan Kochanowicz ◽  
Barbara Mroczko
Keyword(s):  
Multiple Sclerosis ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Control Group ◽  
Free Light Chains ◽  
Pattern Type ◽  
Multiple Sclerosis Patients ◽  
Type 3

Background: It is well known that the cerebrospinal fluid (CSF) concentrations of free light chains (FLC) and immunoglobulin G (IgG) are elevated in multiple sclerosis patients (MS). Therefore, in this study we aimed to develop a model based on the concentrations of free light chains and IgG to predict multiple sclerosis. We tried to evaluate the diagnostic usefulness of the novel κIgG index and λIgG index, here presented for the first time, and compare them with the κFLC index and the λFLC index in multiple sclerosis patients. Methods: CSF and serum samples were obtained from 76 subjects who underwent lumbar puncture for diagnostic purposes and, as a result, were divided into two groups: patients with multiple sclerosis (n = 34) and patients with other neurological disorders (control group; n = 42). The samples were analyzed using turbidimetry and isoelectric focusing. The κIgG index, λIgG index, κFLC index, and λFLC index were calculated using specific formulas. Results: The concentrations of CSF κFLC, CSF λFLC, and serum κFLC and the values of κFLC index, λFLC index, and κIgG index were significantly higher in patients with multiple sclerosis compared to controls. CSF κFLC concentration and the values of κFLC index, λFLC index, and κIgG index differed in patients depending on their pattern type of oligoclonal bands. κFLC concentration was significantly higher in patients with pattern type 2 and type 3 in comparison to those with pattern type 1 and type 4. The κFLC index, λFLC index, and κIgG index were significantly higher in patients with pattern type 2 in comparison to those with pattern type 4. The κFLC index and κIgG index were significantly higher in patients with pattern type 2 in comparison to those with pattern type 1, and in patients with pattern type 3 compared to those with pattern type 4. The κIgG index was markedly elevated in patients with pattern type 3 compared to those with pattern type 1. In the total study group, κFLC, λFLC, κFLC index, λFLC index, κIgG index, and λIgG index correlated with each other. The κIgG index showed the highest diagnostic power (area under the curve, AUC) in the detection of multiple sclerosis. The κFLC index and κIgG index showed the highest diagnostic sensitivity, and the κIgG index presented the highest ability to exclude multiple sclerosis. Conclusion: This study provides novel information about the diagnostic significance of four markers combined in the κIgG index. More investigations in larger study groups are needed to confirm that the κIgG index can reflect the intrathecal synthesis of immunoglobulins and may improve the diagnosis of multiple sclerosis.

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

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.

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

2018 ◽  
Vol 56 (4) ◽  
pp. 609-613 ◽  
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.

Cerebrospinal fluid free light chains determination in oligoclonal bands negative patients with suspected multiple sclerosis

2019 ◽  
Vol 493 ◽  
pp. S616-S617
Author(s):  
D. Ferraro ◽  
P. Natali ◽  
A. Trovati ◽  
R. Bedin ◽  
F. Vitetta ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Free Light Chains

scholarly journals Clinical Use of κ Free Light Chains Index as a Screening Test for Multiple Sclerosis

2020 ◽  
Vol 51 (4) ◽  
pp. 402-407 ◽  
Author(s):  
Luisa Agnello ◽  
Bruna Lo Sasso ◽  
Giuseppe Salemi ◽  
Patrizia Altavilla ◽  
Emanuela Maria Pappalardo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Screening Test ◽  
Neurological Diseases ◽  
Oligoclonal Bands ◽  
Confirmatory Test ◽  
Light Chains ◽  
Clinical Use ◽  
Free Light Chains ◽  
Cutoff Value ◽  
Turbidimetric Assay

Abstract Objective To assess the usefulness of the κ free light chain index (κFLCi) as a screening test to identify patients with suspected MS. Methods The study included 56 patients with a request to test for oligoclonal bands (OCBs). OCBs were detected by isoelectric focusing, followed by immunofixation. Cerebrospinal fluid (CSF) and serum κFLC were measured by a turbidimetric assay. Also, the κFLC index (κFLCi) was calculated. Results CSF κFLC levels and κFLCi were significantly higher in patients with multiple sclerosis (MS) than in patients with other neurological diseases (NDs; P &lt; .001 and P &lt; .001, respectively). At the cutoff value of 2.9, the κFLCi detected MS with sensitivity of 97% and specificity of 65%. Overall, 92% patients with κFLCi of 2.9 or greater and who had tested positive for OCBs were diagnosed as having MS. Conclusion Our findings support the use of κFLCi as a screening test when MS is suspected, followed by OCB detection as a confirmatory test for the diagnosis of MS.

Cerebrospinal fluid free light chains compared to oligoclonal bands as biomarkers in multiple sclerosis

2020 ◽  
Vol 339 ◽  
pp. 577108 ◽  
Author(s):  
Lorenzo Gaetani ◽  
Marinella Di Carlo ◽  
Giovanni Brachelente ◽  
Federico Valletta ◽  
Paolo Eusebi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Free Light Chains

scholarly journals The Persisting Significance of Oligoclonal Bands in the Dawning Era of Kappa Free Light Chains for the Diagnosis of Multiple Sclerosis

2018 ◽  
Vol 19 (12) ◽  
pp. 3796 ◽  
Author(s):  
Philipp Schwenkenbecher ◽  
Franz Konen ◽  
Ulrich Wurster ◽  
Konstantin Jendretzky ◽  
Stefan Gingele ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Light Chain ◽  
Clinically Isolated Syndrome ◽  
Free Light Chain ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Oligoclonal Band ◽  
Free Light Chains ◽  
Mcdonald Criteria

The latest revision of the McDonald criteria of 2017 considers the evidence of an intrathecal immunoglobulin (IgG) synthesis as a diagnostic criterion for dissemination in time in multiple sclerosis. While the detection of oligoclonal bands is considered as the gold standard, determination of kappa free light chains might be a promising tool as a less technically demanding and cost saving method. However, data on the direct comparison between kappa free light chains and oligoclonal bands are limited and no study to date has used the highly sensitive method of polyacrylamide gels with consecutive silver staining for the demonstration of oligoclonal bands. Furthermore, the impact of the revised McDonald criteria of 2017 on the role of kappa free light chains as a biomarker has not been investigated. Nephelometry was used to determine kappa free light chains in cerebrospinal fluid (CSF) and serum from 149 patients with their first demyelinating event between 2010 and 2015. Clinical data, kappa free light chains, and oligoclonal band status were compared at the time of initial diagnosis and after follow-up to identify converters from clinically isolated syndrome to multiple sclerosis. An elevated kappa free light chain index (>5.9) was found in 79/83 patients (95%) with multiple sclerosis diagnosed at baseline, slightly less frequent than oligoclonal bands (98.8%). 18/25 (72%) patients who converted from clinically isolated syndrome to multiple sclerosis showed an elevated kappa free light chain index compared to 20/25 (80%) patients with positive oligoclonal bands. In patients with stable clinically isolated syndrome 7/41 (17%) displayed an elevated kappa free light chain index against 11/41 (27%) oligoclonal band positive patients. Only two patients with stable clinically isolated syndrome showed an elevated kappa free light chain index but were oligoclonal bands negative. In conclusion, determination of the kappa free light chain index is a promising diagnostic approach to assess intrathecal immunoglobulin synthesis in multiple sclerosis. Nevertheless, oligoclonal bands are highly prevalent in multiple sclerosis and can detect an intrathecal synthesis of IgG even when the kappa free light chain index is below the threshold. We consider sequential use of both methods as reasonable.

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