Startseite Quantification of polyclonal free light chains in clinical samples using a single turbidimetric immunoassay
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Quantification of polyclonal free light chains in clinical samples using a single turbidimetric immunoassay

  • Jeffrey M. Faint , Supratik Basu , David Sutton , Paul J. Showell , Philip A. Kalra , Bridget K. Gunson , Colette E. Jackson , Adeel Mushtaq , Lakhvir K. Assi , Hugh D. Carr-Smith , Paul Cockwell und Stephen J. Harding EMAIL logo
Veröffentlicht/Copyright: 13. Juni 2014
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 52 Heft 11

Abstract

Background: Elevated polyclonal serum free light chain (FLC) levels have been associated with increased mortality and disease activity in many conditions. Currently, polyclonal FLC quantification requires summation of individual FLCκ and FLCλ assays. Here we present a single assay for combined FLC (cFLC, Combylite™) which reduces assay time and eliminates potential imprecision errors incurred by summating FLC assays (ΣFLC).

Methods: Sheep FLCκ- and FLCλ-specific antibodies were conjugated to latex microparticles to quantify FLCκ and FLCλ in a single assay. Combylite results were compared to ΣFLC (Freelite®) in 132 healthy controls and 1127 patient samples. The utility of cFLC for predicting all-cause mortality in a haematological referral population was evaluated.

Results: cFLC and ΣFLC results were highly concordant (Passing-Bablok equation y=0.98x–1.59 mg/L, R2=0.96). Combylite assay imprecision was low at concentrations around the upper normal range [coefficient of variation (CV) 5.5%, 54 mg/L] and the upper limit of the measuring range (CV 5.5%, 170 mg/L). cFLC levels were significantly raised in disease states compared with healthy controls. Additionally, cFLC >65 mg/L was associated with shorter overall survival in a haematological referral population (hazard ratio=4.5, p<0.001).

Conclusions: cFLC values obtained using Combylite were comparable to ΣFLC results over a wide concentration range, were elevated in diseases characterised by B cell activation and were associated with increased mortality in a haematological referral population. These observations indicate the Combylite assay has value for investigating the role of B cell activation in disparate disease groups and could be considered as a surrogate indication of B cell function.

Keywords: free light chains; immune response; immunoassay; immunology; renal insufficiency
Corresponding author: Dr. Stephen J. Harding, The Binding Site Group Ltd., 8 Calthorpe Road, Edgbaston, Birmingham, B15 1QT, UK, Phone: +44 121 4569500, Fax: +44 121 4569749, E-mail:

Acknowledgments

The authors would like to thank Chris Buckley for his technical assistance in developing the Combylite assay.

Conflict of interest statement

Authors’ conflict of interest disclosure: Serum Freelite and Combylite kits were provided by The Binding Site Group, Ltd. SB, PAK, PC, DS, BKG, and CEJ have no conflicts of interest. The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding 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.

Research funding: None declared.

Employment or leadership: JMF, LKA, PJS, and AM are employees of and HDC-S and SJH are directors of The Binding Site Group, Ltd.

Honorarium: None declared.

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Received: 2014-3-13
Accepted: 2014-5-20
Published Online: 2014-6-13
Published in Print: 2014-11-19

©2014 by De Gruyter

Artikel in diesem Heft

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  2. Editorial
  3. From symptoms to biomarkers: a change of paradigm
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https://doi.org/10.1515/cclm-2014-0279
Schlagwörter für diesen Artikel
free light chains; immune response; immunoassay; immunology; renal insufficiency

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. From symptoms to biomarkers: a change of paradigm
  4. Reviews
  5. Biochemical markers in early diagnosis and management of systemic amyloidoses
  6. The accuracy of the anti-mitochondrial antibody and the M2 subtype test for diagnosis of primary biliary cirrhosis: a meta-analysis
  7. Genetics and Molecular Diagnostics
  8. Selection of an optimal method for co-isolation of circulating DNA and miRNA from the plasma of pregnant women
  9. General Clinical Chemistry and Laboratory Medicine
  10. Harmonisation of seven common enzyme results through EQA
  11. Harmonization in hemolysis detection and prevention. A working group of the Catalonian Health Institute (ICS) experience
  12. Adopting European Network for Health Technology Assessments (EunetHTA) core model for diagnostic technologies for improving the accuracy and appropriateness of blood gas analyzers’ assessment
  13. Impact of assay design on test performance: lessons learned from 25-hydroxyvitamin D
  14. Anti-ruthenium antibodies mimic macro-TSH in electrochemiluminescent immunoassay
  15. The relationship between the Spine Deformity Index, biochemical parameters of bone metabolism and vascular calcifications: results from the Epidemiological VERtebral FRACtures iTalian Study (EVERFRACT) in dialysis patients
  16. Quantification of polyclonal free light chains in clinical samples using a single turbidimetric immunoassay
  17. Global coagulation tests: their applicability for measuring direct factor Xa- and thrombin inhibition and reversal of anticoagulation by prothrombin complex concentrate
  18. Reference Values and Biological Variations
  19. The importance of individual biology in the clinical use of serum biomarkers for ovarian cancer
  20. The quality of diagnostic testing may be impaired during shipment of lithium-heparin gel tubes
  21. Cancer Diagnostics
  22. Serum human epididymis protein 4 (HE4) as a tumor marker in men with lung cancer
  23. Intestinal permeability in patients with metastatic colon cancer treated with patupilone
  24. Cardiovascular Diseases
  25. European multicenter analytical evaluation of the Abbott ARCHITECT STAT high sensitive troponin I immunoassay
  26. Infectious Diseases
  27. Early indicators of severity and construction of a risk model for prognosis based upon laboratory parameters in patients with hemorrhagic fever with renal syndrome
  28. Corrigendum
  29. Automated indirect immunofluorescence antinuclear antibody analysis is a standardized alternative for visual microscope interpretation
  30. Letters to the Editor
  31. The future of the laboratory information system – what are the requirements for a powerful system for a laboratory data management?
  32. Hypernatraemia in disguise
  33. Interference of therapeutic monoclonal immunoglobulins in the investigation of M-proteins
  34. The impact of exercise on the variation of serum free light chains
  35. Response to Jacobs: N Latex FLC serum free light-chain assays in patients with renal impairment
  36. Reply to Berlanga et al. (DOI 10.1515/cclm-2014-0420)
  37. Mean platelet volume in patients with non-alcoholic fatty liver disease: is mean platelet volume ready as a surrogate marker?
  38. False-positive D-dimer result in a latex-enhanced immunoassay caused by interfering human anti-mouse antibodies
  39. D-Dimer in normal pregnancy: determination of reference values for three commercially available assays
  40. Paraoxonase 2 sequence variation (c.311 C>G) is associated with a modest decrease in circulating LDL size in children and adolescents
  41. The effect of volume of hydrochloric acid preservation on 24-hour urinary catecholamine test
  42. Congress Abstracts
  43. Congress of Clinical Chemistry and Laboratory Medicine
  44. The 3rd EFLM-UEMS Congress
  45. 46th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
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