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Cerebrospinal fluid free light chains as diagnostic biomarker in neuroborreliosis

  • Harald Hegen EMAIL logo , Dejan Milosavljevic , Christine Schnabl , Andrea Manowiecka , Janette Walde , Florian Deisenhammer and Stefan Presslauer
Published/Copyright: April 12, 2018
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 56 Issue 8

Abstract

Background:

Free light chains (FLC) have been proposed as diagnostic biomarker in patients with inflammatory central nervous system diseases. The objective of this study was to investigate the diagnostic utility of intrathecal κ- and λ-FLC synthesis in patients with neuroborreliosis.

Methods:

κ- and λ-FLC were measured by nephelometry under blinded conditions in cerebrospinal fluid (CSF) and serum sample pairs of 34 patients with neuroborreliosis and compared to a cohort of 420 control patients. κ-FLC index was calculated as [CSF κ-FLC/serum κ-FLC]/[CSF albumin/serum albumin], and λ-FLC index in analogy.

Results:

κ-FLC and λ-FLC index were significantly elevated in patients with neuroborreliosis compared to the control group. At a specificity level of 95%, κ-FLC and λ-FLC index showed a diagnostic sensitivity of 88.2% and 100%. In comparison, IgM and IgG synthesis according to Reiber formula, IgG index >0.7 and OCB status reached a sensitivity of 83.9%, 44.1%, 58.8% and 64.7%.

Conclusion:

These findings support the diagnostic value of intrathecal FLC synthesis in neuroborreliosis patients and demonstrate a valid, easy and rater-independent alternative for the detection of an intrathecal immunoglobulin production.

Keywords: cerebrospinal fluid; free light chain; IgA; IgG; IgM; intrathecal synthesis; neuroborreliosis; oligoclonal bands; serum
Corresponding author: Harald Hegen, MD, PhD, Department of Neurology, Medical University of Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria, Phone: +43 512 504 24264, Fax: +43 512 504 24266

  1. Author contributions: H. Hegen has participated in the conception and design of the study, acquisition and statistical analysis of the data, and in drafting the manuscript. D. Milosavljevic has participated in acquisition of the data and in reviewing the manuscript for intellectual content. C. Schnabl has participated in reviewing the manuscript for intellectual content. A. Manowiecka has participated in acquisition of the data and in reviewing the manuscript for intellectual content. J. Walde has participated in statistical analysis of the data and in reviewing the manuscript for intellectual content. F. Deisenhammer has participated in reviewing the manuscript for intellectual content. S. Presslauer has participated in the conception and design of the study and in reviewing the manuscript for intellectual content. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: The study was supported by Siemens, who provided the free light chain immunoassays.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Disclosures: H. Hegen has participated in meetings sponsored by, received speaker honoraria or travel funding from Bayer Schering, Biogen, Merck Serono and Novartis, and received honoraria for acting as consultant for Teva Pharmaceuticals Europe. D. Milosavljevic reports no disclosures. C. Schnabl reports no disclosures. A. Manowiecka reports no disclosures. J. Walde reports no disclosures. F. Deisenhammer has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Biogen, Celgene, Genzyme-Sanofi, Merck, Novartis, Roche, and Teva-Ratiopharm, and received unrestricted research grants from Biogen and Genzyme-Sanofi. S. Presslauer has participated in meetings sponsored by Bayer Schering, Biogen Idec, Merck Serono, Novartis and Teva.

  6. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplementary Material:

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2018-0028).

Received: 2018-01-09
Accepted: 2018-02-26
Published Online: 2018-04-12
Published in Print: 2018-07-26

©2018 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2018-0028
Keywords for this article
cerebrospinal fluid; free light chain; IgA; IgG; IgM; intrathecal synthesis; neuroborreliosis; oligoclonal bands; serum

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. Procalcitonin for diagnosing and monitoring bacterial infections: for or against?
  4. Is it time to abandon the Nobel Prize?
  5. In Memoriam
  6. Norbert Tietz, 13th November 1926–23rd May 2018
  7. Reviews
  8. Procalcitonin guidance in patients with lower respiratory tract infections: a systematic review and meta-analysis
  9. Telomere biology and age-related diseases
  10. Opinion Paper
  11. Procalcitonin-guided antibiotic therapy: an expert consensus
  12. Genetics and Molecular Diagnostics
  13. mRNA expression profile in peripheral blood mononuclear cells based on ADRB1 Ser49Gly and Arg389Gly polymorphisms in essential hypertension — a case-control pilot investigation in South Indian population
  14. General Clinical Chemistry and Laboratory Medicine
  15. External quality assessment schemes for glucose measurements in Germany: factors for successful participation, analytical performance and medical impact
  16. Long-term stability of glucose: glycolysis inhibitor vs. gel barrier tubes
  17. Observational studies on macroprolactin in a routine clinical laboratory
  18. Anti-streptavidin IgG antibody interference in anti-cyclic citrullinated peptide (CCP) IgG antibody assays is a rare but important cause of false-positive anti-CCP results
  19. Point-of-care creatinine testing for kidney function measurement prior to contrast-enhanced diagnostic imaging: evaluation of the performance of three systems for clinical utility
  20. Hematology and Coagulation
  21. Analytical performance of an automated volumetric flow cytometer for quantitation of T, B and natural killer lymphocytes
  22. Lupus anticoagulant testing using two parallel methods detects additional cases and predicts persistent positivity
  23. Reference Values and Biological Variations
  24. Within-subject biological variation of activated partial thromboplastin time, prothrombin time, fibrinogen, factor VIII and von Willebrand factor in pregnant women
  25. Within-subject and between-subject biological variation estimates of 21 hematological parameters in 30 healthy subjects
  26. Immunoglobulin G (IgG) and IgG subclass reference intervals in children, using Optilite® reagents
  27. Cancer Diagnostics
  28. Serum carbohydrate sulfotransferase 7 in lung cancer and non-malignant pulmonary inflammations
  29. Cardiovascular Diseases
  30. Clinical performance of a new point-of-care cardiac troponin I test
  31. Diabetes
  32. Testing for HbA1c, in addition to the oral glucose tolerance test, in screening for abnormal glucose regulation helps to reveal patients with early β-cell function impairment
  33. Effects of common hemoglobin variants on HbA1c measurements in China: results for α- and β-globin variants measured by six methods
  34. Infectious Diseases
  35. Serum procalcitonin concentration within 2 days postoperatively accurately predicts outcome after liver resection
  36. Predictive value of serum gelsolin and Gc globulin in sepsis – a pilot study
  37. Cerebrospinal fluid free light chains as diagnostic biomarker in neuroborreliosis
  38. Letter to the Editor
  39. Glucose and total protein: unacceptable interference on Jaffe creatinine assays in patients
  40. Interference of glucose and total protein on Jaffe-based creatinine methods: mind the covolume
  41. Interference of glucose and total protein on Jaffe based creatinine methods: mind the covolume – reply
  42. Measuring procalcitonin to overcome heterophilic-antibody-induced spurious hypercalcitoninemia
  43. Paraprotein interference in the diagnosis of hepatitis C infection
  44. Timeo apis mellifera and dona ferens: bee sting-induced Kounis syndrome
  45. Bacterial contamination of reusable venipuncture tourniquets in tertiary-care hospital
  46. Detection of EDTA-induced pseudo-leukopenia using automated hematology analyzer with VCS technology
  47. Early adjustment of antimicrobial therapy after PCR/electrospray ionization mass spectrometry-based pathogen detection in critically ill patients with suspected sepsis
  48. Thromboelastometry reveals similar hemostatic properties of purified fibrinogen and a mixture of purified cryoprecipitate protein components
  49. Bicarbonate interference on cobas 6000 c501 chloride ion-selective electrodes
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