Defining Polysaccharide Antibody Deficiency: Measurement of Anti-Pneumococcal Antibodies and Anti-Salmonella typhi Antibodies in a Cohort of Patients with Recurrent Infections
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.
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.
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.
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.
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.
KeywordsPneumococcal polysaccharide vaccine specific antibody deficiency polysaccharide antibody deficiency primary immunodeficiency antibody deficiency Salmonella typhi SAD allohemagglutinins
We thank Marco Baggio for his assistance with the statistical analyses.
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.
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.
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