AUTHOR=Guevara-Hoyer Kissy , Gil Celia , Parker Antony R. , Williams Leigh J. , Orte Carmen , Rodriguez de la Peña Antonia , Ochoa-Grullón Juliana , Rodriguez De Frias Edgard , García Irene Serrano , García-Gómez Sonia , Recio M. José , Fernández-Arquero Miguel , Pérez de Diego Rebeca , Ramos Jose Tomas , Sánchez-Ramón Silvia 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00654

DOI=10.3389/fimmu.2019.00654

ISSN=1664-3224

ABSTRACT=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 (TV) 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 >27 mg/L, whereas only 8% showed TV >28U/mL (p<0.0001). Twenty-one of 28 (75%) achieved a 3-fold increase in post-vaccination TV levels, whereas only 3% achieved a 4-fold increase in post-vaccination PPV, mainly due to high baseline PPV 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 non-responders than in TV 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.