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.
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.
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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).
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Informed consent: Informed consent was obtained from all individuals included in the prospective study.
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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.
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Competing interests: Authors state no conflict of interest.
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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).
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