KFLC Index utility in multiple sclerosis diagnosis: Further confirmation

Pieri, Massimo; Storto, Marianna; Pignalosa, Stefano; Zenobi, Rossella; Buttari, Fabio; Bernardini, Sergio; Centonze, Diego; Dessı̀, Mariarita

doi:10.1016/j.jneuroim.2017.05.007

Cited by 32 publications

(27 citation statements)

References 9 publications

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“…Various studies indicate that high CSF concentrations of kappa FLCs seem to be a more sensitive marker of intrathecal IgG synthesis compared with the finding of CSF-restricted OCBs [5][6][7][8][9][10]15,[18][19][20], although recent studies point to a higher sensitivity of OCB detection [21] or to an equal performance of both tests [22].…”

Section: Discussionmentioning

confidence: 99%

“…FLCs could therefore represent an additional marker of an ongoing oligoclonal humoral immune response within the CNS [4]. Several research groups have demonstrated increased kappa and, to a lesser extent, lambda FLC levels in the cerebrospinal fluid (CSF) of patients with MS [5][6][7][8][9][10]. In particular, FLCs were also detected in the CSF of the small proportion of patients diagnosed with MS without OCBs and in patients with CIS, suggesting that they may be a more sensitive marker of the disease [11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal fluid kappa and lambda free light chains in oligoclonal band‐negative patients with suspected multiple sclerosis

Ferraro

Trovati

Bedin

et al. 2019

Euro J of Neurology

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Background and purpose Cerebrospinal fluid (CSF) kappa free light chains (FLCs) may be a more sensitive marker of intrathecal immunoglobulin (Ig)G synthesis compared with oligoclonal bands (OCBs). Our aim was to retrospectively determine the additional value of the kappa and lambda index (CSF FLC/serum FLC)/(CSF albumin/serum albumin) in predicting a multiple sclerosis (MS) diagnosis in a group of OCB‐negative patients with suspected MS. Methods The CSF and serum kappa and lambda FLCs were tested using the Freelite kit (serum) and Freelite Mx (CSF) assay (The Binding Site Group, Bimingham, UK) in 391 OCB‐negative patients with suspected/possible MS and in 54 OCB‐positive patients with MS. Results The CSF kappa FLC levels were below the detection limit (0.27 mg/L) in 61% of patients. Using quantitative data, we found the best kappa index cut‐off value for the prediction of MS to be 5.8. A kappa index ≥5.8 was present in 25% of OCB‐negative MS (23/92) and in 98% of OCB‐positive patients with MS. Using a qualitative approach and a kappa index cut‐off of 5.9, based on literature data, we likewise found that 24% of OCB‐negative patients with MS had a kappa index ≥5.9, compared with 5.4% of OCB‐negative patients without MS (P < 0.001). No reliable data could be obtained for the lambda index; lambda FLCs were below the detection limit (0.68 mg/L) in 90% of CSF samples. Conclusions The kappa index could contribute to the identification of OCB‐negative patients with a high probability of an MS diagnosis. Using more sensitive techniques might even improve the diagnostic performance of the kappa index and better define the role of the lambda index.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid kappa and lambda free light chains in oligoclonal band‐negative patients with suspected multiple sclerosis

Ferraro

Trovati

Bedin

et al. 2019

Euro J of Neurology

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“…10,14 The KFLC index has comparable sensitivity and specificity to OCB for diagnosis of MS and CIS. 14,21,23 However, large-scale studies comparing diagnostic performance of the two methods and to define the cut-off of FLC are lacking. The main aim of this study was to validate KFLC and LFLC indices as a diagnostic biomarker in MS compared with OCB in a large multicenter study including samples from 18 MS centers across Europe.…”

Section: Introductionmentioning

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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“…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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KFLC Index utility in multiple sclerosis diagnosis: Further confirmation

Cited by 32 publications

References 9 publications

Cerebrospinal fluid kappa and lambda free light chains in oligoclonal band‐negative patients with suspected multiple sclerosis

Cerebrospinal fluid kappa and lambda free light chains in oligoclonal band‐negative patients with suspected multiple sclerosis

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

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