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J Clin Immunol. 2019 Nov 8. doi: 10.1007/s10875-019-00691-8. [Epub ahead of print]

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

Author information

1
Inborn errors of immunity, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
2
Department of Pediatrics, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
3
Department of Pediatric Pulmonology, Infectious Diseases and Primary Immunodeficiencies, Ghent University Hospital, Ghent, Belgium.
4
Department of Microbiology, Immunology and Transplantation, Research group Allergy and Clinical Immunology, KU Leuven, Leuven, Belgium.
5
Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.
6
Clinical and Diagnostic Immunology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
7
Virus and Microbiological Special Diagnostics, Statens Serum Institut, Copenhagen, Denmark.
8
Histocompatibility and Immunogenetic Laboratory, Red Cross Flanders, Mechelen, Belgium.
9
Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
10
Inborn errors of immunity, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium. isabelle.meyts@uzleuven.be.
11
Department of Pediatrics, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. isabelle.meyts@uzleuven.be.

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; SAD; Salmonella typhi; allohemagglutinins; antibody deficiency; polysaccharide antibody deficiency; primary immunodeficiency; specific antibody deficiency

PMID:
31705452
DOI:
10.1007/s10875-019-00691-8

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