Kappa free light chains index in the differential diagnosis of Multiple Sclerosis from Neuromyelitis optica spectrum disorders and other immune-mediated central nervous system disorders

Cavalla, Paola; Caropreso, Paola; Limoncelli, S.; Bosa, Chiara; Pasanisi, Maria Barbara; Schillaci, Valentina; Alteno, Anastasia; Costantini, Gianfranco; Giordana, Maria Teresa; Mengozzi, Giulio; Vercellino, Marco

doi:10.1016/j.jneuroim.2019.577122

Cited by 22 publications

(34 citation statements)

References 16 publications

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“…In addition, it has been previously demonstrated that natalizumab substantially modulates both intrathecal polyclonal and oligoclonal IgG production (Mancuso et al, 2014). Thus, the effect who had significantly lower KFLC index than the MS group (Cavalla et al, 2020). As these conditions are important differential diagnoses to MS, it would be desirable to explore KFLC indices in larger cohorts of neuro-inflammatory CNS diseases.…”

Section: Discussionmentioning

confidence: 99%

Kappa free light chain index as a diagnostic biomarker in multiple sclerosis: A real‐world investigation

Rosenstein

Rasch

Axelsson

et al. 2021

Journal of Neurochemistry

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Section: Discussionmentioning

confidence: 99%

Kappa free light chain index as a diagnostic biomarker in multiple sclerosis: A real‐world investigation

Rosenstein

Rasch

Axelsson

et al. 2021

Journal of Neurochemistry

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“…The only other study so far describing FLC-k values to discriminate patients with MS and NMOSD obtained comparable results with our study cohort. 12 Although using the index method for FLC-k interpretation with the known risk of false positive or negative values 11 and not restricting the cohort of MS to myelitis manifestation, the highest FLC-k index values were seen in patients with MS in comparison to NMOSD. 12 An advantage of FLC-k analysis is the quantification in comparison with the qualitative OCB analysis.…”

Section: Discussionmentioning

confidence: 99%

“…12 Although using the index method for FLC-k interpretation with the known risk of false positive or negative values 11 and not restricting the cohort of MS to myelitis manifestation, the highest FLC-k index values were seen in patients with MS in comparison to NMOSD. 12 An advantage of FLC-k analysis is the quantification in comparison with the qualitative OCB analysis. We could identify an IF of 78.6% with a sensitivity of 88.9% and a specificity of 88.5% to discriminate patients with myelitis due to MS and NMOSD.…”

Section: Discussionmentioning

confidence: 99%

Free light chains kappa can differentiate between myelitis and noninflammatory myelopathy

Süße

Feistner

Grothe

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo test the hypothesis that the intrathecal synthesis of free light chain kappa (FLC-k) can be used as a CSF biomarker to differentiate patients with myelitis due to multiple sclerosis (MS), myelitis due to neuromyelitis optica spectrum disease (NMOSD), and noninflammatory myelopathy, we analyzed FLC-k in 26 patients with MS myelitis, 9 patients with NMOSD myelitis, and 14 patients with myelopathy.MethodsThis is a retrospective monocentric cohort study. FLC-k were analyzed using the nephelometric Siemens FLC-k kit in paired samples of CSF and sera. Intrathecal fraction (IF) of FLC-k was plotted in a FLC-k quotient diagram.ResultsNinety-six percent of patients with MS myelitis had an intrathecal synthesis of FLC-k in comparison with 55.6% for NMOSD and 14.3% of patients with noninflammatory myelopathy. The locally synthesized absolute amount of FLC-k was significantly higher in patients with myelitis due to MS than in patients with NMOSD (p = 0.038) or noninflammatory myelopathy (p < 0.0001). The sensitivity of FLC-k synthesis to detect inflammation in patients with myelitis is 85.7%. Using a receiver operating characteristic analysis, FLC-k IF >78% can discriminate patients with myelitis due to MS and NMOSD with a sensitivity of 88.5% and a specificity of 88.9%ConclusionsWith the hyperbolic reference range in quotient diagrams for FLC-k, it is possible to distinguish inflammatory myelitis from noninflammatory myelopathies. An FLC-k IF >78% can be a hint to suspect myelitis due to MS rather than NMOSD.

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“…Furthermore, different studies investigated patient-related impact factors on the concentration of KFLC and whether or not a significant correlation between patient sex, age and KFLC concentrations might exist [18,50,71,72,74,78,81]. In some studies, a correlation between increasing patient age and decreasing KFLC indices was observed with higher indices in female patients [18,71,81]. Pieri et al investigated gender-specific KFLC index threshold-values and found a cut-off of 12.5 for women and 11 for men [81].…”

Section: Influencing Factors For Flc and Impact On Laboratory Analysis Proceduresmentioning

confidence: 99%

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

Konen

Schwenkenbecher

Jendretzky

et al. 2021

Cells

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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.

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Kappa free light chains index in the differential diagnosis of Multiple Sclerosis from Neuromyelitis optica spectrum disorders and other immune-mediated central nervous system disorders

Cited by 22 publications

References 16 publications

Kappa free light chain index as a diagnostic biomarker in multiple sclerosis: A real‐world investigation

Kappa free light chain index as a diagnostic biomarker in multiple sclerosis: A real‐world investigation

Free light chains kappa can differentiate between myelitis and noninflammatory myelopathy

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

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