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

Valencia-Vera, Estefanía; Martínez-Escribano, Ana; Enguix, Alfredo; Abalos-Garcia, Carmen; Segovia-Cuevas, Maria Jesus

doi:10.1515/cclm-2017-0285

Cited by 39 publications

(31 citation statements)

References 14 publications

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“…The cut-off in this study was calculated using a data-driven Gaussian mixture modeling approach. We chose a different approach compared to other studies that applied, for example, receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) values, 9 , 10 , 18 , 23 , 27 , 32 because we reasoned that the cut-off should be defined by biological levels (data driven) and not based on clinical diagnosis, which is an imperfect golden standard. We determined a cut-off of 6.6 for abnormal KFLC indices and 6.9 for abnormal LFLC indices.…”

Section: Discussionmentioning

confidence: 99%

Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

et al. 2019

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Objective: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). Methods: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. Results: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2–138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5–22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85–0.90) was higher than OCB (0.82; 95%CI = 0.79–0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78–0.88) was lower (OCB = 0.92; 95% CI = 0.89–0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Conclusion: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.

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Section: Discussionmentioning

confidence: 99%

Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

et al. 2019

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“…There is a growing body of evidence suggesting that determination of CSF KFLC is a valuable quantitative alternative or complement to the qualitative assessment of OCB. [5][6][7][8][9][10][11][12][13][14][15][16] But KFLC can be presented in many different ways, as the pure CSF concentration or in more complex metrics where the permeability of the blood-brain barrier and the different kinetics of the molecules passing that barrier is taken into account. There is currently no consensus as to which metric to be used in a clinical setting.…”

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confidence: 99%

Diagnostic accuracy of intrathecal kappa free light chains compared with OCBs in MS

Duell

Evertsson

Nimer

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo determine what kappa free light chain (KFLC) metric has the highest capacity to separate healthy patients from patients with MS, we evaluated the sensitivity, specificity, and the overall diagnostic accuracy of 4 different KFLC metrics. To assess the usefulness of KFLC in the diagnostics of MS, we compared the different KFLC metrics with oligoclonal bands (OCBs), the current gold standard biochemical method to demonstrate intrathecal antibody production.MethodsCSF and plasma were collected from patients with confirmed or suspected MS, other neurological diseases, as well as symptomatic and healthy controls between May 2017 and May 2018 (n = 335) at the Department of Neurology, Karolinska University Hospital, as part of routine diagnostic workup. KFLC analysis and isoelectric focusing for the detection of oligoclonal bands (OCB) were determined and correlated with diagnosis. Receiver operating characteristic (ROC) curve analysis was used to determine accuracy.ResultsOCBs yielded a sensitivity of 87% and a specificity of 100%. All KFLC metrics showed a high sensitivity (89%–95%) and specificity (95%–100%). Using the optimal cutoff according to the Youden Index resulted for the KFLC intrathecal fraction in a cutoff of −0.41 with a sensitivity of 95% and a specificity of 97% and for CSF KFLC/CSF albumin with a cutoff of 1.93 × 10−3 with a sensitivity of 94% and specificity of 100%.ConclusionAll evaluated KFLC metrics have excellent accuracy, and both KFLC intrathecal fraction and CSF KFLC/CSF albumin are at least as good as OCB in separating patients with MS from a control group.Classification of evidenceThis study provides Class III evidence that CSF KFLC accurately distinguishes patients with MS from healthy controls.

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“…Various studies comparing the diagnostic accuracy of the kappa index and OCB for a MS diagnosis found similar results, with the kappa index being slightly more sensitive and less specific compared to OCB [ 8 , 9 , 10 , 11 ], although not all studies are concordant [ 12 , 13 , 14 ]. The sensitivity and specificity of both kappa index and OCB found in the present study was lower compared to the existing literature, which reports values up to 100% for either sensitivity or specificity [ 15 ].…”

Section: Discussionmentioning

confidence: 87%

Kappa Index versus CSF Oligoclonal Bands in Predicting Multiple Sclerosis and Infectious/Inflammatory CNS Disorders

et al. 2020

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Background: Cerebrospinal fluid (CSF) kappa free light chains (KFLC) are gaining increasing interest as markers of intrathecal immunoglobulin synthesis. The main aim of this study was to assess the diagnostic accuracy (AUC) of the kappa index (CSF/serum KFLC divided by the CSF/serum albumin ratio) compared to CSF oligoclonal IgG bands (OCB) in predicting Multiple Sclerosis (MS) or a central nervous system infectious/inflammatory disorder (CNSID). Methods: We enrolled patients who underwent a diagnostic spinal tap throughout two years. KFLC levels were determined using a Freelite assay (Binding Site) and the turbidimetric Optilite analyzer. Results: Of 540 included patients, 223 had a CNSID, and 84 had MS. The kappa index was more sensitive (0.89 versus 0.85) and less specific (0.84 versus 0.89), with the same AUC (0.87) as OCB for MS diagnosis (optimal cut-off: 6.2). Adding patients with a single CSF IgG band to the OCB-positive group slightly increased the AUC (0.88). Likewise, the kappa index (cut-off: 3.9) was more sensitive (0.67 versus 0.50) and less specific (0.81 versus 0.97), with the same AUC (0.74) as OCB, for a CNSID diagnosis. Conclusion: The kappa index and CSF OCB have comparable diagnostic accuracies for a MS or CNSID diagnosis and supply the clinician with useful, complementary information.

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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

Abstract: 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.

Cited by 39 publications

References 14 publications

Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

Diagnostic accuracy of intrathecal kappa free light chains compared with OCBs in MS

Kappa Index versus CSF Oligoclonal Bands in Predicting Multiple Sclerosis and Infectious/Inflammatory CNS Disorders

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