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Combined deficient response to polysaccharide-based and protein-based vaccines predicts a severe clinical phenotype

  • Maaike Cockx ORCID logo , Filomeen Haerynck , Levi Hoste , Rik Schrijvers , Jutte Van der Werff ten Bosch , Doreen Dillaerts , Debby Thomas , Heidi Schaballie , Giorgia Bucciol , Wiert Robberechts , Dina Patel , Guy Berbers , Isabelle Desombere , Nick Geukens , Isabelle Meyts and Xavier Bossuyt EMAIL logo
Published/Copyright: September 21, 2023
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 62 Issue 1

Abstract

Objectives

Antibody response on polysaccharide- and protein-based vaccines is useful to test B cell functionality. As only few studies have explored the value of studying immune response to both vaccines, we evaluated the clinical value of anti-polysaccharide and anti-protein Luminex-based multiplex assays in context of primary immunodeficiency (PID) diagnosis.

Methods

A 10-plex Luminex-based assay detecting antibodies to ten pneumococcal polysaccharide (PnPS) serotypes [present in unconjugated Pneumovax, not in 13-valent pneumococcal conjugated vaccine (PCV)] and a 5-plex assay detecting antibodies to five protein antigens (present in DTap/Tdap) were clinically validated in healthy individuals (n=99) and in retrospective (n=399) and prospective (n=108) patient cohorts. Clinical features of individuals with impaired response to PnPS and/or proteins were compared to those with normal response.

Results

Antigen-specific antibody thresholds were determined in healthy individuals. Individuals with impaired anti-PnPS responses and deficient immunoglobulin levels suffered more from autoimmune diseases and had lower B cell levels compared to individuals with impaired anti-PnPS response with normal immunoglobulin levels. Individuals with combined impaired response to PnPS and proteins showed more severe clinical manifestations compared to individuals with isolated impaired response to PnPS or proteins. Eight of the 11 individuals with severely impaired responses to both PnPS and proteins had common variable immunodeficiency. Evaluation of the anti-PnPS response to four serotypes not contained in 20-valent PCV was comparable to evaluation to ten serotypes not contained in 13-valent PCV.

Conclusions

Multiplexed assessment of anti-PnPS and anti-protein responses combined with immunoglobulin quantification provides useful clinical information to support PID diagnosis.

Keywords: DTaP/Tdap vaccine; multiplex assays; PCV15/20; pneumococcal polysaccharides; Pneumovax; primary immunodeficiency diagnosis
Corresponding author: Xavier Bossuyt, Department of Microbiology, Immunology and Transplantation, University of Leuven, Leuven, Belgium; PharmAbs, The KU Leuven Antibody Center, University of Leuven, Leuven, Belgium; and Laboratory of Clinical and Diagnostic Immunology, Herestraat 49a, 3000 Leuven, Belgium, Phone: +32 16/34.70.09, Fax: +32 16/34.70.09, E-mail:

Funding source: Fonds Wetenschappelijk Onderzoek

Award Identifier / Grant number: T003716N

Acknowledgments

We would like to thank professor Bob Meek and Ben De Jong from Sint-Antonius Hospital (Nieuwegein, the Netherlands), the group of professor Guy Berbers and Pieter Van Gageldonck (Infection & Immunity, Utrecht, the Netherlands) and corporation Luminex corp. (the Netherlands) for the technical assistance in the optimization of the Luminex-based assays. In addition, we would like to thank Kasper Cockx  for his assistance in the statistical analysis of the data.

  1. Research ethics: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of UZ Leuven, UZ Ghent and UZ Brussels (Date 01/01/2017/No S60027).

  2. Informed consent: Informed consent was obtained from all individuals included in the prospective study.

  3. Author contributions: Xavier Bossuyt and Nick Geukens contributed to the study concept and design. Material preparation, data collection and analysis were performed by Maaike Cockx, Doreen Dillaerts and Debby Thomas. The first draft of the manuscript was written by Maaike Cockx and Xavier Bossuyt and all authors commented on previous versions of the manuscript. Isabelle Desombere and Guy Berbers provided technical assistance during multiplex assay optimization. Filomeen Haerynck, Levi Hoste, Isabelle Meyts, Giorgia Bucciol, Rik Schrijvers, Jutte Van der Werff ten Bosch and Wiert Robberechts collected serum samples of individuals for the prospective study. Clinical data collection and analysis were performed by Maaike Cockx, Levi Hoste and Wiert Robberechts. Isabelle Meyts and Heidi Schaballie provided the serum samples of the healthy control group. All authors read and approved the final manuscript.

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

  5. Research funding: This project was supported by Research Foundation Flanders (FWO) – Applied Biomedical Research (TBM) (T003716N). FWO senior clinical investigator fellowships: RS: 1805518N and 1805523N.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2023-0626).

Received: 2023-06-15
Accepted: 2023-08-31
Published Online: 2023-09-21
Published in Print: 2024-01-26

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2023-0626
Keywords for this article
DTaP/Tdap vaccine; multiplex assays; PCV15/20; pneumococcal polysaccharides; Pneumovax; primary immunodeficiency diagnosis

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Biological management of diabetes mellitus, the laboratory medicine specialist and the patient
  4. Reviews
  5. Remote HbA1c testing via microsampling: fit for purpose?
  6. The effect of hormonal contraceptive therapy on clinical laboratory parameters: a literature review
  7. Opinion Paper
  8. Continuous glucose monitoring has an increasing role in pre-symptomatic type 1 diabetes: advantages, limitations, and comparisons with laboratory-based testing
  9. IFCC Paper
  10. Comparison and commutability study among four faecal immunochemical tests (FIT) systems
  11. Guidelines and Recommendations
  12. Evidence-based procedures to improve the reliability of circulating miRNA biomarker assays
  13. General Clinical Chemistry and Laboratory Medicine
  14. Commutability assessment of candidate reference materials for plasma renin activity measurement: current challenges
  15. Aggregated data from the same laboratories participating in two glucose external quality assessment schemes show that commutability and transfers of values to control materials are decisive for the biases found
  16. Methodological considerations in determining sex steroids in children: comparison of conventional immunoassays with liquid chromatography-tandem mass spectrometry
  17. From “wet” matrices to “dry” blood spot sampling strategy: a versatile LC-MS/MS assay for simultaneous monitoring caffeine and its three primary metabolites in preterm infants
  18. A sensitive LC-MS/MS methotrexate assay capable of assessing adherence to methotrexate therapy in rheumatoid arthritis
  19. Determination of cortisone and cortisol in human scalp hair using an improved LC-MS/MS-based method
  20. Mild hypophosphatasia may be twice as prevalent as previously estimated: an effective clinical algorithm to detect undiagnosed cases
  21. Combined deficient response to polysaccharide-based and protein-based vaccines predicts a severe clinical phenotype
  22. Reference Values and Biological Variations
  23. A sex-specific association of leukocyte telomere length with thigh muscle mass
  24. Cancer Diagnostics
  25. Optimized procedure for high-throughput transcriptome profiling of small extracellular vesicles isolated from low volume serum samples
  26. Ultra-short cell-free DNA fragments enhance cancer early detection in a multi-analyte blood test combining mutation, protein and fragmentomics
  27. Clinical relevance of clonal hematopoiesis and its interference in cell-free DNA profiling of patients with gastric cancer
  28. Development and analytical validation of a novel nasopharynx swab-based Epstein-Barr virus C promoter methylation quantitative assay for nasopharyngeal carcinoma detection
  29. Infectious Diseases
  30. (Pre)analytical considerations concerning the analysis of synovial calprotectin
  31. Corrigendum
  32. Thermal and chronological stability of monocyte distribution width (MDW), the new biomarker for sepsis
  33. Acknowledgment
  34. Acknowledgment
  35. Letters to the Editor
  36. In-house diagnostic devices under the EU IVDR and unwanted side-effects of intentional transparency
  37. Use of thyroid function tests in urine: a position statement of the Belgian Thyroid Club
  38. State of the art of measurement uncertainty of serum ferritin
  39. Analytical performance evaluation and consumable waste reduction strategies using a tube-based quality control material
  40. Stability of fecal calprotectin extracts using the Diasorin® kit
  41. Reverse cascade testing from newborn screening: the opportunity to improve family healthcare outcomes
  42. An indirect data-mining approach to standardise paediatric serum phosphate reference intervals in Wales
  43. Sodium and risk assessment of osmotic demyelination syndrome: the method matters!
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