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

Schwenkenbecher, Philipp; Konen, Franz Felix; Wurster, Ulrich; Jendretzky, Konstantin Fritz; Gingele, Stefan; Sühs, Kurt‐Wolfram; Pul, Refik; Witte, Torsten; Stangel, Martin; Skripuletz, Thomas

doi:10.3390/ijms19123796

Cited by 37 publications

(41 citation statements)

References 21 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%

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%

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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“…Patients were included when they were either newly diagnosed with MS according to the 2017 McDonald criteria or converted to MS during follow-up. Some of these patients were previously investigated with a focus on different other aspects [14][15][16][17][18]. A total of 107 patients were included.…”

Section: Retrospectively Collected Datamentioning

confidence: 99%

The Impact of Immunomodulatory Treatment on Kappa Free Light Chains as Biomarker in Neuroinflammation

Konen

Wurster

Witte

et al. 2020

Cells

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Background: Kappa free light chains (KFLC) are a promising new biomarker to detect neuroinflammation. Still, the impact of pre-analytical effects on KFLC concentrations was not investigated. Methods: KFLC concentrations were measured in serum and cerebrospinal fluid (CSF) of patients with a newly diagnosed multiple sclerosis (MS) or clinically isolated syndrome (CIS) before (n = 42) or after therapy with high-dose methylprednisolone (n = 65). In prospective experiments, KFLC concentrations were analyzed in the same patients in serum before and after treatment with high-dose methylprednisolone (n = 16), plasma exchange (n = 12), immunoadsorption (n = 10), or intravenous immunoglobulins (n = 10). In addition, the influence of storage time, sample method, and contamination of CSF with blood were investigated. Results: Patients diagnosed with MS/CIS and treated with methylprednisolone showed significantly lower KFLC concentrations in serum as untreated patients. Repeated longitudinal investigations revealed that serum KFLC concentrations continuously decreased after each application of methylprednisolone. In contrast, other immune therapies and further pre-analytical conditions did not influence KFLC concentrations. Conclusion: Our results show prominent effects of steroids on KFLC concentrations. In contrast, various other pre-analytical conditions did not influence KFLC concentrations, indicating the stability of this biomarker.

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“…7837_BO_K_2018, approved on 6 April 2018). A subset of this cohort (147 patients) was previously described in studies in which the role of KFLC index and oligoclonal bands as biomarker in MS were investigated [12][13][14].…”

Section: Patientsmentioning

confidence: 99%

Reiber’s Diagram for Kappa Free Light Chains: The New Standard for Assessing Intrathecal Synthesis?

et al. 2019

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Oligoclonal bands are the gold standard for determination of an intrathecal immunoglobulin G synthesis and were recently included in the McDonald criteria of 2017 to diagnose relapsing multiple sclerosis (MS) as a substitute for dissemination in time. Intrathecally produced kappa free light chains (KFLC) are a novel promising biomarker with similar characteristics and the advantage for automated determination. However, different approaches exist to determine the intrathecal KFLC fraction. The most common method is to calculate the CSF/serum KFLC quotient with reference to the albumin CSF/serum quotient (QKappa/QAlb) the so-called KFLC index. Recently, Reiber developed a theoretically and empirically founded hyperbolic function similar to his traditional hyperbolic function for the immunoglobulins A, G, M. Our study included a total of 168 patients with either MS according to the McDonald criteria of 2017, clinically isolated syndrome (CIS) with conversion to MS during follow-up, or stable CIS. Positive oligoclonal bands were compared with the KFLC index, Reiber’s KFLC diagram, Presslauer’s KFLC exponential curve, and Senel’s linear curve for KFLC. Reiber’s diagram detected an intrathecal production of KFLC in 98/100 patients with MS, only one patient fewer than oligoclonal bands positivity (99/100). By using the KFLC index ≥ 5.9, Presslauer’s KFLC exponential function, and Senel’s linear curve two more patients would not have been identified (96/100). For the group of patients who converted from CIS to MS similar results were obtained for both the oligoclonal bands and the Reiber graph (21/24, 88%). The KFLC index ≥ 5.9, Presslauer’s method, and Senel’s linear function each identified two patients fewer (19/24, 79%). In patients with stable CIS, 11/44 patients (25%) displayed oligoclonal bands in contrast to 9/44 patients (20%) with elevated KFLC by using Reiber’s diagram and Presslauer’s method, 8/44 patients (18%) with elevated KFLC as detected by Senel’s linear function, and 7/44 patients (16%) with KFLC index ≥ 5.9. In conclusion, Reiber’s KFLC diagram shows a great diagnostic performance to detect an intrathecal KFLC production in patients with MS.

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

Cited by 37 publications

References 21 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

The Impact of Immunomodulatory Treatment on Kappa Free Light Chains as Biomarker in Neuroinflammation

Reiber’s Diagram for Kappa Free Light Chains: The New Standard for Assessing Intrathecal Synthesis?

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