Measurement of Pneumococcal Polysaccharide Vaccine Responses for Immunodeficiency Diagnostics: Combined IgG Responses Compared to Serotype Specific IgG Responses

Janssen, Willemijn J.M.; Bloem, Andries C.; Vellekoop, P.; Boes, Marianne; Montfrans, Joris M. van

doi:10.1007/s10875-013-9925-y

Cited by 17 publications

(13 citation statements)

References 12 publications

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“…The great inter-serotype heterogeneity of the anti-PnPS response in a given patient and the large inter-patient heterogeneity for a given serotype (as illustrated in Figure S1 in Supplementary Material) have long been recognized as important issues in assessment of anti-PnPS responses ( 9 , 10 ). An isolated, elevated response to a single serotype may indeed be responsible for a high OVA value ( 18 ) (Figure S1 in Supplementary Material).…”

Section: Discussionmentioning

confidence: 99%

Value of the Overall Pneumococcal Polysaccharide Response in the Diagnosis of Primary Humoral Immunodeficiencies

et al. 2017

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BackgroundAn overall response assay [OVA, based on a 23-valent pneumococcal polysaccharide vaccine (PPV23)] is widely used to screen for anti-pneumococcal antibodies. Given the heterogeneity of response from one polysaccharide (PS) to another, a World Health Organization-standardized serotype-specific enzyme-linked immunosorbent assay (SSA) is considered to be the only reliable method for testing anti-PS antibody responses in individuals with suspected primary immunodeficiencies (PIDs).ObjectiveTo evaluate the OVA relative to the reference SSA.MethodsSerum samples of adult patients referred for a suspected PID were collected before and then 4–8 weeks after immunization with PPV23. The anti-pneumococcal response was systematically assessed with an SSA (7–16 serotypes) and interpreted according to the American Academy of Asthma, Allergy and Immunology’s current guidelines. We used receiver operating characteristic curves and agreement indices to assess the OVA’s diagnostic value in a first cohort. In order to validate these findings, a second (validation) cohort was then prospectively included.ResultsSixty-two adult patients were included, and 42 (67.7%) were defined as poor responders according to the SSA. Only the post-immunization titer in the OVA was able to correctly identify poor responders; a titer below 110 mg/L gave a positive predictive value of 100% [identifying 24 (57.1%) of the 42 poor responders], and similar levels of diagnostic performance were observed in the validation cohort. The pre-vaccination antibody titer, the post/pre-vaccination antibody titer ratio and a post-vaccination titer above 110 mg/L in the OVA were not predictive of the response in the SSA.ConclusionA post-vaccination antibody titer below 110 mg/L in the OVA was constantly associated with a poor PPV23 response using the SSA. In all other cases, SSA is the only reliable method for assessing diagnostic vaccination with PPV23.

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Section: Discussionmentioning

confidence: 99%

Value of the Overall Pneumococcal Polysaccharide Response in the Diagnosis of Primary Humoral Immunodeficiencies

et al. 2017

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“…In our study, we observed that baseline levels of PPV were high at pre-vaccination in up to one-third of patients tested, which could be a reflection of the antibodies generated in previous vaccination against pneumococcal conjugate vaccine. When pre-vaccination titers are already high, immune capacity may be normal despite low “fold-increase” (2, 8, 20). Therefore, a 4-fold increase post vaccination in these children is not to be expected.…”

Section: Discussionmentioning

confidence: 99%

“…This could be a confounding factor in determining the production of polysaccharide antibodies if only the gold standard is used, as these individuals did not generate the expected response increase (FI ≥ 4) despite being immunocompetent, which makes it difficult to interpret. While it is true that measuring isolated serotypes against pneumococcus is a useful tool in this regard, in particular in patients with total IgG PPV response >40 mg/L (20), at present no center in Spain actually perform this for routine purposes.…”

Section: Discussionmentioning

confidence: 99%

Measurement of Typhim Vi IgG as a Diagnostic Tool to Determine Anti-polysaccharide Antibody Production Deficiency in Children

Guevara-Hoyer

Gil

Parker³

et al. 2019

Front. Immunol.

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Background: The assessment of specific polysaccharide antibody production plays a pivotal role in the diagnosis of humoral primary immunodeficiencies (PID). The response to 23-valent pneumococcal vaccine (PPV) remains the gold standard for the diagnosis of polysaccharide antibodies. However, in Spain, the interpretation of pure polysaccharide 23-valent immunization is hampered by the high endemicity of pneumococcal disease and the generalization of the 13-valent adjuvant pneumococcal vaccination. Specific Typhim Vi vaccination (TV) immunoglobulin G IgG response to immunization is useful in adult PID, but there is no data regarding children. Objectives: To evaluate the clinical utility of TV IgG production as a diagnostic tool to determine anti-polysaccharide antibody production deficiency in children, when the response to PPV is unclear and isolated determination of serotypes is unfeasible. Methods: We conducted a single-institution prospective observational study on 61 children with recurrent infections. Baseline specific antibodies against PPV and TV were evaluated. In 28 children (46%), the response to the production of antibodies confirmed a clinical suspicion of humoral PID, and they were therefore immunized with 23-valent pneumococcal vaccine and Typhim Vi. Both specific antibody responses were measured by ELISA (The Binding Site Group Ltd, Birmingham, UK) using previously published cut-offs. Results: Seventy percent of the 61 children displayed baseline PPV IgG > 27 mg/L, whereas only 8% showed TV IgG > 28 U/mL ( p < 0.0001). Twenty-one of 28 children (75%) achieved a 3-fold increase in post-vaccination TV IgG levels, whereas only 3% achieved a 4-fold increase in PPV IgG post vaccination, mainly due to high baseline PPV IgG titers. When we classified children according to their response to TV as responders or non-responders and compared this with the well-known clinical warning signs of the Jeffrey Modell Foundation. The proportions of children with history of pneumonia and the need for intravenous antibiotics were significantly higher in TV IgG non-responders than in TV IgG responders ( p = 0.02 and p = 0.01, respectively). Conclusion: Response to TV can be considered an ancillary diagnostic tool to determine polysaccharide antibodies in children, particularly when isolated determination of pneumococcal serotypes is not feasible. TV provides a useful asset for clinicians in the era of conjugate PPV vaccination, with clinical relevance. Further research is warranted for validation.

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“…Some authors recommend measurement of serotype specific antibody responses. However, these measurements are available only in specialized laboratories …”

Section: Current Classification Of Igg Subclass Deficienciesmentioning

confidence: 99%

“…However, these measurements are available only in specialized laboratories. 12,13 Why is the vaccine response of tremendous importance? Even with normal Ig isotypes and normal IgG subclasses children may have increased susceptibility to infections and absent polysaccharide responses, known as specific antibody deficiency (SAD).…”

Section: Children With Absent or Low Antibody Responses Regardless Omentioning

confidence: 99%

IgG subclass deficiencies in children: Facts and fiction

Wahn

Bernuth

2017

Pediatric Allergy Immunology

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Measurement of Pneumococcal Polysaccharide Vaccine Responses for Immunodeficiency Diagnostics: Combined IgG Responses Compared to Serotype Specific IgG Responses

Cited by 17 publications

References 12 publications

Value of the Overall Pneumococcal Polysaccharide Response in the Diagnosis of Primary Humoral Immunodeficiencies

Value of the Overall Pneumococcal Polysaccharide Response in the Diagnosis of Primary Humoral Immunodeficiencies

Measurement of Typhim Vi IgG as a Diagnostic Tool to Determine Anti-polysaccharide Antibody Production Deficiency in Children

IgG subclass deficiencies in children: Facts and fiction

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