Marie Süße1, Hansotto Reiber2, Matthias Grothe1, Astrid Petersmann3, Matthias Nauck4, Alexander Dressel5, Malte Johannes Hannich6. 1. Departement of Neurology, University Medicine Greifswald, Greifswald, Germany. 2. CSF and Complexity Studies, Göttingen and University Göttingen, Germany. 3. Institute of Clinical Chemistry, University Göttingen, Germany. 4. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. 5. Departement of Neurology, Carl-Thiem Klinikum Cottbus, Germany. 6. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. Electronic address: malte.hannich@med.uni-greifswald.de.
Abstract
OBJECTIVES: Free light chain kappa (FLC-k) in cerebrospinal fluid (CSF) is involved in intrathecal immune responses and is being investigated frequently for its diagnostic sensitivity. The objective of this study was the application and interpretation of FLC-k data in quotient diagrams with a hyperbolic reference range and to confirm the superior evaluation in comparison with another proposed reference method and cut-off values. Secondly, the performance of the FLC-k quotient diagram was analyzed in respect to MS and CIS patients and in relation to the polyspecific immune response. MATERIALS AND METHODS: FLC-k was analyzed in a control cohort (n = 302) and in patients with MS/CIS (n = 98) using a nephelometric FLC-k kit. The intrathecal fraction of FLC-k based on the hyperbolic reference range was calculated in comparison to various linear FLC-k indices and routine CSF parameters [oligoclonal bands (OCB), polyspecific antiviral immune response]. RESULTS: Using the new hyperbolic reference range, intrathecal FLC-k synthesis was found in 20 / 302 OCB negative controls. The sensitivity in the definitive MS cohort was 100%, compared to 93% positive OCB. The linear FLC-k Index interpretation with similar sensitivity for MS, however, bares the risk for the control samples,depending on the reference range, of false positive interpretations (up to 7 at low QAlb) or false negative interpretations (up to 17/20 FLC-k positives at high QAlb). The quantitative mean intrathecal FLC-k synthesis in the CIS cohort (later MS) was even slightly higher than in initially definitive MS questioning a pathophysiological difference. A positive MRZ reaction found in 53% percent of CIS patients with intrathecal FLC-k synthesis could have allowed diagnosis of MS immediately, i.e. earlier than with the Mc Donald criteria. CONCLUSIONS: The evaluation of FLC-k with hyperbolic reference range in quotient diagrams is superior to other analytical methods like the linear FLC-k index. We suggest a sequential CSF testing with FLC-k Reibergram evaluation, potentially followed by isoelectric focusing. With the MRZ reaction we obtain highest specificity for MS diagnosis.
OBJECTIVES: Free light chain kappa (FLC-k) in cerebrospinal fluid (CSF) is involved in intrathecal immune responses and is being investigated frequently for its diagnostic sensitivity. The objective of this study was the application and interpretation of FLC-k data in quotient diagrams with a hyperbolic reference range and to confirm the superior evaluation in comparison with another proposed reference method and cut-off values. Secondly, the performance of the FLC-k quotient diagram was analyzed in respect to MS and CIS patients and in relation to the polyspecific immune response. MATERIALS AND METHODS:FLC-k was analyzed in a control cohort (n = 302) and in patients with MS/CIS (n = 98) using a nephelometric FLC-k kit. The intrathecal fraction of FLC-k based on the hyperbolic reference range was calculated in comparison to various linear FLC-k indices and routine CSF parameters [oligoclonal bands (OCB), polyspecific antiviral immune response]. RESULTS: Using the new hyperbolic reference range, intrathecal FLC-k synthesis was found in 20 / 302 OCB negative controls. The sensitivity in the definitive MS cohort was 100%, compared to 93% positive OCB. The linear FLC-k Index interpretation with similar sensitivity for MS, however, bares the risk for the control samples,depending on the reference range, of false positive interpretations (up to 7 at low QAlb) or false negative interpretations (up to 17/20 FLC-k positives at high QAlb). The quantitative mean intrathecal FLC-k synthesis in the CIS cohort (later MS) was even slightly higher than in initially definitive MS questioning a pathophysiological difference. A positive MRZ reaction found in 53% percent of CIS patients with intrathecal FLC-k synthesis could have allowed diagnosis of MS immediately, i.e. earlier than with the Mc Donald criteria. CONCLUSIONS: The evaluation of FLC-k with hyperbolic reference range in quotient diagrams is superior to other analytical methods like the linear FLC-k index. We suggest a sequential CSF testing with FLC-k Reibergram evaluation, potentially followed by isoelectric focusing. With the MRZ reaction we obtain highest specificity for MS diagnosis.
Authors: Marie Süße; Fritz Feistner; Matthias Grothe; Matthias Nauck; Alexander Dressel; Malte Johannes Hannich Journal: Neurol Neuroimmunol Neuroinflamm Date: 2020-09-18
Authors: Franz Felix Konen; Philipp Schwenkenbecher; Konstantin Fritz Jendretzky; Stefan Gingele; Kurt-Wolfram Sühs; Hayrettin Tumani; Marie Süße; Thomas Skripuletz Journal: Cells Date: 2021-11-06 Impact factor: 6.600
Authors: Franz F Konen; Philipp Schwenkenbecher; Ulrich Wurster; Konstantin F Jendretzky; Nora Möhn; Stefan Gingele; Kurt-Wolfram Sühs; Malte J Hannich; Matthias Grothe; Torsten Witte; Martin Stangel; Marie Süße; Thomas Skripuletz Journal: J Cent Nerv Syst Dis Date: 2021-11-19
Authors: Franz Felix Konen; Philipp Schwenkenbecher; Konstantin Fritz Jendretzky; Stefan Gingele; Torsten Witte; Kurt-Wolfram Sühs; Matthias Grothe; Malte Johannes Hannich; Marie Süße; Thomas Skripuletz Journal: Brain Sci Date: 2022-04-03
Authors: Franz Felix Konen; Malte Johannes Hannich; Philipp Schwenkenbecher; Matthias Grothe; Konrad Gag; Konstantin Fritz Jendretzky; Stefan Gingele; Kurt-Wolfram Sühs; Torsten Witte; Thomas Skripuletz; Marie Süße Journal: Biomedicines Date: 2022-07-07
Authors: Marie Süße; Franz Felix Konen; Philipp Schwenkenbecher; Kathrin Budde; Matthias Nauck; Matthias Grothe; Malte Johannes Hannich; Thomas Skripuletz Journal: Diagnostics (Basel) Date: 2022-03-16