Startseite Implications of monoclonal gammopathy and isoelectric focusing pattern 5 on the free light chain kappa diagnostics in cerebrospinal fluid
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Implications of monoclonal gammopathy and isoelectric focusing pattern 5 on the free light chain kappa diagnostics in cerebrospinal fluid

  • Malte J. Hannich EMAIL logo , Franz F. Konen , Konrad Gag , Aiham Alkhayer , Seda N. Türker , Kathrin Budde , Matthias Nauck , Ulrich Wurster , Alexander Dressel , Thomas Skripuletz und Marie Süße
Veröffentlicht/Copyright: 23. Juli 2024
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 63 Heft 1

Abstract

Objectives

Oligoclonal bands (OCB) analysis is the reference standard for detecting an intrathecal IgG synthesis. Alongside OCB, free light chains kappa (FLCκ) are considered an additional sensitive biomarker for determining patterns 2 or 3, indicating intrathecal Ig synthesis. However, kFLC IF is not suitable for detecting a monoclonal pattern 5. The primary aim of this study was to evaluate the impact of incorporating FLCκ analysis into routine cerebrospinal fluid (CSF) diagnostics instead of OCB testing on the rate of missed monoclonal IgG detection.

Methods

A two-center retrospective biomarker study was conducted. OCB were identified using isoelectric focusing in polyacrylamide gels followed by silver staining or in agarose gels followed by immunofixation. FLCκ were quantified using nephelometry and FLCκ assay (Siemens).

Results

Out of a combined total of 17,755 OCB analyses conducted between 2011 and 2021, a subset of 269 cases (1.5 %) exhibited pattern 5. 98 samples (36 %), which included 18 samples with intrathecal inflammation as determined by additional OCB pattern 2 were included in the FLCκ analysis. Of those, 16 (89 %) had intrathecal FLCκ synthesis.

Conclusions

While FLCκ offers a promising avenue for detecting an intrathecal inflammation, the pattern 5, though rare, remains a valuable additional finding of OCB analysis. A combined approach of FLCκ and OCB analysis is recommended for a comprehensive assessment of the humoral intrathecal immune response.

Keywords: cerebrospinal fluid; intrathecal immunoglobulin synthesis; free light chain kappa; oligoclonal IgG; pattern 5; monoclonal gammopathy
Corresponding author: Malte J. Hannich, Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany; and Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany, E-mail:
Malte Johannes Hannich, Franz F. Konen, Thomas Skripuletz and Marie Süße contributed equally to this work.

  1. Research ethics: This study was performed in accordance with the Declaration of Helsinki and was approved by the local Ethics Committee (III UV 39/03; University Medicine Greifswald, Greifswald, Germany (UMG), Greifswald, Germany; Hannover Medical School, Hannover, Germany (MHH): No. 7837_BO_K_2018, April 6, 2018).

  2. Informed consent: Not applicable.

  3. Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission. Conceptualization: MS. Data curation: MS, MH, KG, AA. Formal analysis: MH, MS, UW, FK. Writing – original draft: MH, MS. Writing – review & editing: MS, MH, KG, FK, AD, KB, MN, UW, TS.

  4. Competing interests: The authors state no conflict of interest. Outside the submitted work, the authors received honoraria for lectures, travel grants, or research grants. FFK reports travel grants from Merck and Novartis. MS reports personal fees and grants from Merck Healthcare Deutschland and Bayer Vital GmbH. TS received grants from Bristol Myers Squibb and Sanofi Aventis and personal fees from Alexion, Alnylam, Bayer Vital, Biogen, Celgene, CSL Behring, EUROIMMUN, Merck, Novartis, Roche, Sanofi Aventis, and Siemens. MN reports nonfinancial support by Siemens Healthineers, The Binding Site Group, Becton Dickinson, DZHK (German Centre for Cardiovascular Research, Partner Site Greifswald, University Medicine, Greifswald, Germany), DGKL (German Federation of Clinical Chemistry and Laboratory Medicine), German Federal Medical Association, Roche Diagnostics Germany GmbH; he also received personal fees by Boehringer Ingelheim and Becton Dickinson; Grant by DZHK, LVL technologies, Bruker BioSpin, Abbott, Radiometer, Tosoh and IDS Immunodiagnostic Systems Deutschland GmbH.

  5. Research funding: None declared.

  6. Data availability: The raw data can be obtained on request from the corresponding author.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2023-1468).

Received: 2023-12-18
Accepted: 2024-06-27
Published Online: 2024-07-23
Published in Print: 2025-01-29

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2023-1468
Schlagwörter für diesen Artikel
cerebrospinal fluid; intrathecal immunoglobulin synthesis; free light chain kappa; oligoclonal IgG; pattern 5; monoclonal gammopathy

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Blood self-sampling: friend or foe?
  4. Reviews
  5. Blood self-sampling devices: innovation, interpretation and implementation in total lab automation
  6. Salivary fatty acids in humans: a comprehensive literature review
  7. Opinion Papers
  8. EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) recommendations for reinforcing cyber-security and managing cyber-attacks in medical laboratories
  9. Point-of-care testing: state-of-the art and perspectives
  10. A standard to report biological variation data studies – based on an expert opinion
  11. Ethical Checklists for Clinical Research Projects and Laboratory Medicine: two tools to evaluate compliance with bioethical principles in different settings
  12. Guidelines and Recommendations
  13. Assessment of cardiovascular risk and physical activity: the role of cardiac-specific biomarkers in the general population and athletes
  14. Genetics and Molecular Diagnostics
  15. Clinical utility of regions of homozygosity (ROH) identified in exome sequencing: when to pursue confirmatory uniparental disomy testing for imprinting disorders?
  16. An ultrasensitive DNA-enhanced amplification method for detecting cfDNA drug-resistant mutations in non-small cell lung cancer with selective FEN-assisted degradation of dominant somatic fragments
  17. General Clinical Chemistry and Laboratory Medicine
  18. The biological variation of insulin resistance markers: data from the European Biological Variation Study (EuBIVAS)
  19. The surveys on quality indicators for the total testing process in clinical laboratories of Fujian Province in China from 2018 to 2023
  20. Preservation of urine specimens for metabolic evaluation of recurrent urinary stone formers
  21. Performance evaluation of a smartphone-based home test for fecal calprotection
  22. Implications of monoclonal gammopathy and isoelectric focusing pattern 5 on the free light chain kappa diagnostics in cerebrospinal fluid
  23. Development and validation of a novel 7α-hydroxy-4-cholesten-3-one (C4) liquid chromatography tandem mass spectrometry method and its utility to assess pre-analytical stability
  24. Establishment of ELISA-comparable moderate and high thresholds for anticardiolipin and anti-β2 glycoprotein I chemiluminescent immunoassays according to the 2023 ACR/EULAR APS classification criteria and evaluation of their diagnostic performance
  25. Reference Values and Biological Variations
  26. Capillary blood parameters are gestational age, birthweight, delivery mode and gender dependent in healthy preterm and term infants
  27. Reference intervals and percentiles for soluble transferrin receptor and sTfR/log ferritin index in healthy children and adolescents
  28. Cancer Diagnostics
  29. Detection of serum CC16 by a rapid and ultrasensitive magnetic chemiluminescence immunoassay for lung disease diagnosis
  30. Cardiovascular Diseases
  31. The role of functional vitamin D deficiency and low vitamin D reservoirs in relation to cardiovascular health and mortality
  32. Annual Reviewer Acknowledgment
  33. Reviewer Acknowledgment
  34. Letters to the Editor
  35. EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) survey on cybersecurity
  36. Comment on Lippi et al.: EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) recommendations for reinforcing cyber-security and managing cyber-attacks in medical laboratories
  37. Six Sigma in laboratory medicine: the unfinished symphony
  38. Navigating complexities in vitamin D and cardiovascular health: a call for comprehensive analysis
  39. Simplified preanalytical laboratory procedures for therapeutic drug monitoring (TDM) in patients treated with high-dose methotrexate (HD-MTX) and glucarpidase
  40. New generation of Abbott enzyme assays: imprecision, methods comparison, and impact on patients’ results
  41. Correction of negative-interference from calcium dobesilate in the Roche sarcosine oxidase creatinine assay using CuO
  42. Two cases of MTHFR C677T polymorphism typing failure by Taqman system due to MTHFR 679 GA heterozygous mutation
  43. A falsely elevated blood alcohol concentration (BAC) related to an intravenous administration of phenytoin sodium
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