Focusing on good responders to pneumococcal polysaccharide vaccination in general hospital patients suspected for immunodeficiency: A decision tree based on the 23-valent pneumococcal IgG assay

L.M.A. Janssen, M. Heron, J-L. Murk, A.C.A.P. Leenders, G.T. Rijkers, E. de Vries

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Background and Aim:
Recently, the 23-valent IgG-assay was suggested as screening assay to identify poor responders to pneumococcal polysaccharide (PnPS)-vaccination with the serotype-specific assay as a second-line test. However, in a low pre-test probability general hospital setting predicting good responders could be more valuable to reduce the number of samples needing serotyping.

Methods:
Serotype-specific PnPS antibody-assays were performed for suspected immunodeficiency in two Dutch general hospitals (Jeroen Bosch Hospital, 's-Hertogenbosch; Elisabeth Tweesteden Hospital, Tilburg). 23-Valent PnPS antibody-assays were subsequently performed in archived material. Data were analyzed using receiver operating characteristic curves (AUC) and agreement indices (ICC).

Results:
Sera of 284 patients (348 samples) were included; 23-valent IgG-titres and the corresponding sum of PnPS-serotype specific antibodies showed moderate correlation (ICC = 0.63). In 232 conjugated-pneumococcal-vaccine-naïve patients (270 samples), a random 23-valent IgG-titer could discriminate between samples with and without ≥7/11, ≥7/13, or ≥6/9 pneumococcal serotypes when both cut-off values 0.35 and 1.0 μg/ml were used (AUC 0.86 and 0.92, respectively). All patients with a pre-immunization-titer ≥38.2 μg/ml and/or post-immunization-titer ≥96.1 μg/ml and none with a post-immunization-titer ≤38.5 μg/ml exhibited a good response to PnPS vaccination. Using these breakpoints as screening test to predict good responders, only 24% of patients would require further serotyping, as opposed to 68% if breakpoints to predict poor responders would have been used.

Conclusion:
In a low pre-test probability setting, the 23-valent IgG-assay proved to be a reliable screening test for good responders in conjugated-pneumococcal-vaccine-naïve patients, reducing the overall number of patient samples needing further serotyping, thus reducing overall costs of pneumococcal vaccination response assessment.
Original languageEnglish
Article number2496
Number of pages10
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - 2019

Fingerprint

Decision Trees
General Hospitals
Area Under Curve
Serogroup
Serum

Keywords

  • 23-valent IgG assay
  • ANALYTICAL VARIABILITY
  • ANTIBODY-RESPONSE
  • CAPSULAR POLYSACCHARIDE
  • CLINICAL INTERPRETATION
  • HEALTHY-CHILDREN
  • VaccZyme (TM)
  • humoral immunodeficiency
  • pneumococcal polysaccharide response
  • pneumococcal vaccination response
  • polysaccharide response
  • primary immunodeficiency
  • serotype-specific assay

Cite this

@article{d114a4bce6364206a7e010c161f38c7b,
title = "Focusing on good responders to pneumococcal polysaccharide vaccination in general hospital patients suspected for immunodeficiency: A decision tree based on the 23-valent pneumococcal IgG assay",
abstract = "Background and Aim: Recently, the 23-valent IgG-assay was suggested as screening assay to identify poor responders to pneumococcal polysaccharide (PnPS)-vaccination with the serotype-specific assay as a second-line test. However, in a low pre-test probability general hospital setting predicting good responders could be more valuable to reduce the number of samples needing serotyping.Methods: Serotype-specific PnPS antibody-assays were performed for suspected immunodeficiency in two Dutch general hospitals (Jeroen Bosch Hospital, 's-Hertogenbosch; Elisabeth Tweesteden Hospital, Tilburg). 23-Valent PnPS antibody-assays were subsequently performed in archived material. Data were analyzed using receiver operating characteristic curves (AUC) and agreement indices (ICC).Results: Sera of 284 patients (348 samples) were included; 23-valent IgG-titres and the corresponding sum of PnPS-serotype specific antibodies showed moderate correlation (ICC = 0.63). In 232 conjugated-pneumococcal-vaccine-na{\"i}ve patients (270 samples), a random 23-valent IgG-titer could discriminate between samples with and without ≥7/11, ≥7/13, or ≥6/9 pneumococcal serotypes when both cut-off values 0.35 and 1.0 μg/ml were used (AUC 0.86 and 0.92, respectively). All patients with a pre-immunization-titer ≥38.2 μg/ml and/or post-immunization-titer ≥96.1 μg/ml and none with a post-immunization-titer ≤38.5 μg/ml exhibited a good response to PnPS vaccination. Using these breakpoints as screening test to predict good responders, only 24{\%} of patients would require further serotyping, as opposed to 68{\%} if breakpoints to predict poor responders would have been used.Conclusion: In a low pre-test probability setting, the 23-valent IgG-assay proved to be a reliable screening test for good responders in conjugated-pneumococcal-vaccine-na{\"i}ve patients, reducing the overall number of patient samples needing further serotyping, thus reducing overall costs of pneumococcal vaccination response assessment.",
keywords = "23-valent IgG assay, ANALYTICAL VARIABILITY, ANTIBODY-RESPONSE, CAPSULAR POLYSACCHARIDE, CLINICAL INTERPRETATION, HEALTHY-CHILDREN, VaccZyme (TM), humoral immunodeficiency, pneumococcal polysaccharide response, pneumococcal vaccination response, polysaccharide response, primary immunodeficiency, serotype-specific assay",
author = "L.M.A. Janssen and M. Heron and J-L. Murk and A.C.A.P. Leenders and G.T. Rijkers and {de Vries}, E.",
year = "2019",
doi = "10.3389/fimmu.2019.02496",
language = "English",
volume = "10",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S.A.",

}

Focusing on good responders to pneumococcal polysaccharide vaccination in general hospital patients suspected for immunodeficiency : A decision tree based on the 23-valent pneumococcal IgG assay. / Janssen, L.M.A.; Heron, M.; Murk, J-L.; Leenders, A.C.A.P.; Rijkers, G.T.; de Vries, E.

In: Frontiers in Immunology, Vol. 10, 2496, 2019.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Focusing on good responders to pneumococcal polysaccharide vaccination in general hospital patients suspected for immunodeficiency

T2 - A decision tree based on the 23-valent pneumococcal IgG assay

AU - Janssen, L.M.A.

AU - Heron, M.

AU - Murk, J-L.

AU - Leenders, A.C.A.P.

AU - Rijkers, G.T.

AU - de Vries, E.

PY - 2019

Y1 - 2019

N2 - Background and Aim: Recently, the 23-valent IgG-assay was suggested as screening assay to identify poor responders to pneumococcal polysaccharide (PnPS)-vaccination with the serotype-specific assay as a second-line test. However, in a low pre-test probability general hospital setting predicting good responders could be more valuable to reduce the number of samples needing serotyping.Methods: Serotype-specific PnPS antibody-assays were performed for suspected immunodeficiency in two Dutch general hospitals (Jeroen Bosch Hospital, 's-Hertogenbosch; Elisabeth Tweesteden Hospital, Tilburg). 23-Valent PnPS antibody-assays were subsequently performed in archived material. Data were analyzed using receiver operating characteristic curves (AUC) and agreement indices (ICC).Results: Sera of 284 patients (348 samples) were included; 23-valent IgG-titres and the corresponding sum of PnPS-serotype specific antibodies showed moderate correlation (ICC = 0.63). In 232 conjugated-pneumococcal-vaccine-naïve patients (270 samples), a random 23-valent IgG-titer could discriminate between samples with and without ≥7/11, ≥7/13, or ≥6/9 pneumococcal serotypes when both cut-off values 0.35 and 1.0 μg/ml were used (AUC 0.86 and 0.92, respectively). All patients with a pre-immunization-titer ≥38.2 μg/ml and/or post-immunization-titer ≥96.1 μg/ml and none with a post-immunization-titer ≤38.5 μg/ml exhibited a good response to PnPS vaccination. Using these breakpoints as screening test to predict good responders, only 24% of patients would require further serotyping, as opposed to 68% if breakpoints to predict poor responders would have been used.Conclusion: In a low pre-test probability setting, the 23-valent IgG-assay proved to be a reliable screening test for good responders in conjugated-pneumococcal-vaccine-naïve patients, reducing the overall number of patient samples needing further serotyping, thus reducing overall costs of pneumococcal vaccination response assessment.

AB - Background and Aim: Recently, the 23-valent IgG-assay was suggested as screening assay to identify poor responders to pneumococcal polysaccharide (PnPS)-vaccination with the serotype-specific assay as a second-line test. However, in a low pre-test probability general hospital setting predicting good responders could be more valuable to reduce the number of samples needing serotyping.Methods: Serotype-specific PnPS antibody-assays were performed for suspected immunodeficiency in two Dutch general hospitals (Jeroen Bosch Hospital, 's-Hertogenbosch; Elisabeth Tweesteden Hospital, Tilburg). 23-Valent PnPS antibody-assays were subsequently performed in archived material. Data were analyzed using receiver operating characteristic curves (AUC) and agreement indices (ICC).Results: Sera of 284 patients (348 samples) were included; 23-valent IgG-titres and the corresponding sum of PnPS-serotype specific antibodies showed moderate correlation (ICC = 0.63). In 232 conjugated-pneumococcal-vaccine-naïve patients (270 samples), a random 23-valent IgG-titer could discriminate between samples with and without ≥7/11, ≥7/13, or ≥6/9 pneumococcal serotypes when both cut-off values 0.35 and 1.0 μg/ml were used (AUC 0.86 and 0.92, respectively). All patients with a pre-immunization-titer ≥38.2 μg/ml and/or post-immunization-titer ≥96.1 μg/ml and none with a post-immunization-titer ≤38.5 μg/ml exhibited a good response to PnPS vaccination. Using these breakpoints as screening test to predict good responders, only 24% of patients would require further serotyping, as opposed to 68% if breakpoints to predict poor responders would have been used.Conclusion: In a low pre-test probability setting, the 23-valent IgG-assay proved to be a reliable screening test for good responders in conjugated-pneumococcal-vaccine-naïve patients, reducing the overall number of patient samples needing further serotyping, thus reducing overall costs of pneumococcal vaccination response assessment.

KW - 23-valent IgG assay

KW - ANALYTICAL VARIABILITY

KW - ANTIBODY-RESPONSE

KW - CAPSULAR POLYSACCHARIDE

KW - CLINICAL INTERPRETATION

KW - HEALTHY-CHILDREN

KW - VaccZyme (TM)

KW - humoral immunodeficiency

KW - pneumococcal polysaccharide response

KW - pneumococcal vaccination response

KW - polysaccharide response

KW - primary immunodeficiency

KW - serotype-specific assay

U2 - 10.3389/fimmu.2019.02496

DO - 10.3389/fimmu.2019.02496

M3 - Article

VL - 10

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 2496

ER -