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C-reactive protein interacts with amphotericin B liposomes and its potential clinical consequences

  • Joris R. Delanghe ORCID logo EMAIL logo , Jonas Himpe , Jerina Boelens , Dominique Benoit , Bram Gadeyne , Marijn M. Speeckaert und Frederick Verbeke
Veröffentlicht/Copyright: 25. Januar 2023
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 61 Heft 6

Abstract

Objectives

Amphotericin B (AmB) is the gold standard for treating invasive fungal infections. New liposomal-containing AmB formulations have been developed to improve efficacy and tolerability. Serum/plasma C-reactive protein (CRP) values are widely used for monitoring infections and inflammation. CRP shows a high affinity to phosphocholine and it aggregates structures bearing this ligand, e.g. phosphocholine-containing liposomes. Therefore, we studied the interaction between CRP and phosphocholine-containing liposomal AmB preparations in vivo and in vitro.

Methods

CRP was prepared by affinity chromatography. Liposomal AmB (L-AmB, AmBisome®) was spiked (final concentrations of L-AmB: 150 mg/L) to CRP-containing serum (final CRP concentration: 300 mg/L). Following the addition of L-AmB, complex formation was monitored turbidimetrically. The size of CRP-L-AmB complexes was assessed using gel filtration. CRP was monitored in patients receiving either L-Amb or AmB lipid complex (ABLC).

Results

Following addition of L-AmB to CRP-containing plasma, turbidimetry showed an increase in absorbance. These results were confirmed by gel permeation chromatography. Similarly, in vivo effects were observed following intravenous administration of AmBisome®: a decline in CRP values was observed. In patients receiving L-Amb, decline of CRP concentration was faster than in patients receiving ABLC.

Conclusions

In vitro experiments are suggestive of a complexation between CRP and liposomes in plasma. Interpretation of CRP values following administration of AmBisome® might be impaired due to this complexation. In vivo formation of complexes between liposomes and CRP might contribute, or even lead, to intravascular microembolisation. Similar effects have been described following the administration of Intralipid® and other phosphocholine-containing liposomes.

Keywords: amphotericin B; C-reactive protein; complexes; gel permeation chromatography; phosphocholine
Corresponding author: Prof. Dr. Joris R. Delanghe, Department of Diagnostic Sciences, Ghent University, De Pintelaan 185, B 9000, Ghent, Belgium, Phone: ++ 32 9 332 2956, Fax: ++ 32 9 332 3659, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The local Institutional Review Board deemed the study exempt from review.

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Received: 2022-11-26
Accepted: 2023-01-13
Published Online: 2023-01-25
Published in Print: 2023-05-25

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2022-1213
Schlagwörter für diesen Artikel
amphotericin B; C-reactive protein; complexes; gel permeation chromatography; phosphocholine

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Improving access to diagnostic testing in conflict-affected areas: what is needed?
  4. Review
  5. Deciphering the role of monocyte and monocyte distribution width (MDW) in COVID-19: an updated systematic review and meta-analysis
  6. Opinion Paper
  7. From research cohorts to the patient – a role for “omics” in diagnostics and laboratory medicine?
  8. EFLM Paper
  9. The European Register of Specialists in Clinical Chemistry and Laboratory Medicine: code of conduct, version 3 – 2023
  10. Guidelines and Recommendations
  11. Cardiac troponin measurement at the point of care: educational recommendations on analytical and clinical aspects by the IFCC Committee on Clinical Applications of Cardiac Bio-Markers (IFCC C-CB)
  12. Genetics and Molecular Diagnostics
  13. A new and improved method of library preparation for non-invasive prenatal testing: plasma to library express technology
  14. Multiplex proteomics using proximity extension assay for the identification of protein biomarkers predictive of acute graft-vs.-host disease in allogeneic hematopoietic cell transplantation
  15. General Clinical Chemistry and Laboratory Medicine
  16. Assessment of laboratory capacity in conflict-affected low-resource settings using two World Health Organization laboratory assessment tools
  17. Challenge in hyponatremic patients – the potential of a laboratory-based decision support system for hyponatremia to improve patient’s safety
  18. Evaluation of hemolysis, lipemia, and icterus interference with common clinical immunoassays
  19. Serum bicarbonate stability study at room temperature – influence of time to centrifugation and air exposure on bicarbonate measurement reported according to the CRESS checklist
  20. Effects of lipemia on capillary serum protein electrophoresis in native ultra-lipemic material and intravenous lipid emulsion added sera
  21. C-reactive protein interacts with amphotericin B liposomes and its potential clinical consequences
  22. Evaluation of analytical performance of homocysteine LC-MS/MS assay and design of internal quality control strategy
  23. A reliable and high throughput HPLC–HRMS method for the rapid screening of β-thalassemia and hemoglobinopathy in dried blood spots
  24. Dynamics of the vitamin D C3-epimer levels in preterm infants
  25. Comparison of ANA testing by indirect immunofluorescence or solid-phase assays in a low pre-test probability population for systemic autoimmune disease: the Camargo Cohort
  26. Reference Values and Biological Variations
  27. LMS-based continuous reference percentiles for 14 laboratory parameters in the CALIPER cohort of healthy children and adolescents
  28. Indirectly determined reference intervals for automated white blood cell differentials of pediatric patients in Berlin and Brandenburg
  29. Infectious Diseases
  30. Evaluation of a high-sensitivity SARS-CoV-2 antigen test on the fully automated light-initiated chemiluminescent immunoassay platform
  31. Letters to the Editor
  32. Non-esterified fatty acids (NEFA): sample stability and effect of haemolysis and icterus
  33. Frozen serum sample pool should not be used as internal quality assessment for lipemia (L) index
  34. Stability of SARS-CoV-2 respiratory samples in non-freezing condition: importance for tropical countries under heavy diagnostic demand
  35. A rare case of both macro-TSH and macro-LH: laboratory analysis of the pathogenesis
  36. A new method for early cancer detection based on platelet transcriptomics will have low positive predictive value
  37. Comparison of near-infrared and UV–vis-based non-contact hematocrit prediction of dried blood spots from patients on immunosuppressants
  38. The diagnostics of heparin-induced thrombocytopenia in Italy and the possible impact of vaccine-induced immune thrombotic thrombocytopenia on it
  39. Pitfall in the analysis of the alcohol biomarkers ethyl glucuronide and ethyl sulfate by laboratory-caused contamination with disinfectants
  40. Growing your own food is like printing money, don’t let it make you mad as a hatter
  41. Congress Abstracts
  42. 43rd annual conference of the association of clinical biochemists in Ireland (ACBI 2021)
  43. 44th Annual Conference of the Association of Clinical Biochemists in Ireland (ACBI 2022)
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