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Defining Polysaccharide Antibody Deficiency: Measurement of Anti-Pneumococcal Antibodies and Anti-Salmonella typhi Antibodies in a Cohort of Patients with Recurrent Infections

  • Giorgia Bucciol
  • Heidi Schaballie
  • Rik Schrijvers
  • Barbara Bosch
  • Marijke Proesmans
  • Kris De Boeck
  • Mieke Boon
  • François Vermeulen
  • Natalie Lorent
  • Doreen Dillaerts
  • Bjørn Kantsø
  • Charlotte Svaerke Jørgensen
  • Marie-Paule Emonds
  • Xavier Bossuyt
  • Leen Moens
  • Isabelle MeytsEmail author
Original Article

Abstract

Background

The correlation between different methods for the detection of pneumococcal polysaccharide vaccine (PPV) responses to diagnose specific polysaccharide antibody deficiency (SAD) is poor and the criteria for defining a normal response lack consensus. We previously proposed fifth percentile (p5) values of PPV responses as a new cutoff for SAD.

Objective

To analyze the association of SAD (determined by either World Health Organization (WHO)-standardized ELISA or multiplex bead-based assay) with abnormal response to Salmonella (S.) typhi Vi vaccination in a cohort of patients with recurrent infections.

Methods

Ninety-four patients with a clinical history suggestive of antibody deficiency received PPV and S. typhi Vi vaccines. Polysaccharide responses to either 3 or 18 pneumococcal serotypes were measured by either the WHO ELISA or a multiplex in-house bead-based assay. Anti-S. typhi Vi IgG were measured by a commercial ELISA kit. Allohemagglutinins (AHA) were measured by agglutination method.

Results

Based on the American Academy of Allergy, Asthma and Immunology (AAAAI) criteria for WHO ELISA, 18/94 patients were diagnosed with SAD and 22/93 based on serotype-specific p5 cutoffs for bead-based assay. The association between the two methods was significant, with 10 subjects showing abnormal response according to both techniques. Abnormal response to S. typhi Vi vaccination was found in 7 patients, 6 of which had SAD. No correlation was found between polysaccharide response and AHA, age, or clinical phenotype.

Conclusion

The lack of evidence-based gold standards for the diagnosis of SAD represents a challenge in clinical practice. In our cohort, we confirmed the insufficient correlation between different methods of specific PPV response measurement, and showed that the S. typhi Vi response was not contributive. Caution in the interpretation of results is warranted until more reliable diagnostic methods can be validated.

Keywords

Pneumococcal polysaccharide vaccine specific antibody deficiency polysaccharide antibody deficiency primary immunodeficiency antibody deficiency Salmonella typhi SAD allohemagglutinins 

Notes

Acknowledgments

We thank Marco Baggio for his assistance with the statistical analyses.

Author Contributions

HS and IM designed the study. HS conducted the experiments and revised the manuscript. GB analyzed and interpreted the data and prepared the manuscript. LM helped with data interpretation and critically revised the manuscript. IM, HS, RS, MP, KDB, BB, MB, FV, and NL enrolled the patients and critically revised the manuscript. DD, BK, CJ, M-PE, and XB performed laboratory measures and critically revised the manuscript.

Funding Information

GB is supported by the Research Foundation - Flanders (project G0C8517N). HS is supported by a PhD fellowship grant of the Research Foundation - Flanders. RS is supported by a senior clinical investigator fund of the Research Foundation - Flanders. IM is supported by the Jeffrey Modell Foundation, by the Research Foundation - Flanders (project G0C8517N), and is holder of the CSL Behring Chair in Primary Immunodeficiency in Children. This work is supported by a GOA grant of the KU Leuven. The Binding Site (Birmingham, UK) provided the ELISA kits for measuring S. typhi antibodies.

Compliance with Ethical Standards

The study was approved by the ethical committee of the hospital and written informed consent was obtained from the patients or their parents.

Conflict of Interest

IM is supported by a CSL Behring Chair in Primary Immunodeficiency, paid to institution. The other authors have no conflict of interest to declare.

Supplementary material

10875_2019_691_MOESM1_ESM.docx (540 kb)
ESM 1 (DOCX 540 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Giorgia Bucciol
    • 1
    • 2
  • Heidi Schaballie
    • 1
    • 2
    • 3
  • Rik Schrijvers
    • 4
  • Barbara Bosch
    • 2
  • Marijke Proesmans
    • 2
  • Kris De Boeck
    • 2
  • Mieke Boon
    • 2
  • François Vermeulen
    • 2
  • Natalie Lorent
    • 5
  • Doreen Dillaerts
    • 6
  • Bjørn Kantsø
    • 7
  • Charlotte Svaerke Jørgensen
    • 7
  • Marie-Paule Emonds
    • 8
  • Xavier Bossuyt
    • 6
    • 9
  • Leen Moens
    • 1
  • Isabelle Meyts
    • 1
    • 2
    Email author
  1. 1.Inborn errors of immunity, Department of Microbiology, Immunology and TransplantationKU LeuvenLeuvenBelgium
  2. 2.Department of PediatricsUniversity Hospitals LeuvenLeuvenBelgium
  3. 3.Department of Pediatric Pulmonology, Infectious Diseases and Primary ImmunodeficienciesGhent University HospitalGhentBelgium
  4. 4.Department of Microbiology, Immunology and Transplantation, Research group Allergy and Clinical ImmunologyKU LeuvenLeuvenBelgium
  5. 5.Department of Respiratory DiseasesUniversity Hospitals LeuvenLeuvenBelgium
  6. 6.Clinical and Diagnostic Immunology, Department of Microbiology, Immunology and TransplantationKU LeuvenLeuvenBelgium
  7. 7.Virus and Microbiological Special DiagnosticsStatens Serum InstitutCopenhagenDenmark
  8. 8.Histocompatibility and Immunogenetic LaboratoryRed Cross FlandersMechelenBelgium
  9. 9.Department of Laboratory MedicineUniversity Hospitals LeuvenLeuvenBelgium

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