Abstract
Assessment of specific antibody (Ab)production to polysaccharide antigens is clinically relevant, identifying patients at risk for infection by encapsulated bacteria and thus enabling a more rigorous selection of patients that can benefit of immunoglobulin replacement therapy. Classically, the gold-standard test is the measurement of antibody production to pure polysaccharide pneumococcal (PPV)immunization. Several factors, including introduction of conjugate vaccination schedule, serotyping analysis, high baseline Ablevels, have hinderedthe evaluation of polysaccharide antigens. This is even more difficult in secondary immunodeficiencies (SID), where patients can show secondary responses despite lack of primary antibody responses and present withrecurrent or severe infections. Assessmentof specific Ab production to pure Salmonella typhi Vipolysaccharide(TV) immunizationhasbeen proposed as a complementary test to PPV, given its low seroprevalence.Toset theoptimalcut-offvalue for PPVand TVresponse in SID,we tested different biostatistical methodologies, including ROC analysis, Youden index, Union index and Closest-topleft in a cohort of 42 SID patients and 24 healthycontrols. The statistically chosen cut-offs valuepre-post TVAbratio was≥5, (sensitivity of 90%,specificity of 100%) and a postvaccination TV concentration of 28.5 U/mL (sensitivity of 90%, specificity of 95%), showing relevant clinical correlate.
Highlights
Impairment of specific antibody (Ab) responses characterizes a wide number of primary (PID) and secondary (SID) immunodeficiencies, rendering individuals susceptible to recurrent and severe infections, mainly by encapsulated bacteria as well as rare opportunistic pathogens [1,2,3]
Receiver operating characteristic (ROC) curve defines the optimal cut-off as the point maximizing the product of sensitivity and specificity when a continuous variable is considered as a diagnostic biomarker
typhi Vi polysaccharide vaccine (TV) responses could be useful in secondary immunodeficiencies (SID) patients, which were previous immunocompetent, and in which pneumococcal polysaccharide vaccine (PPV) may show normal secondary responses but lack primary responses and present with recurrent or severe infections
Summary
Impairment of specific antibody (Ab) responses characterizes a wide number of primary (PID) and secondary (SID) immunodeficiencies, rendering individuals susceptible to recurrent and severe infections, mainly by encapsulated bacteria as well as rare opportunistic pathogens [1,2,3]. Assessment of specific Ab responses is clinically relevant and enable a more rigorous selection of patients that can benefit of immunoglobulin replacement therapy (IgRT). Diagnostic assessment of humoral T-cell independent responses is classically performed by measuring Ab responses to polysaccharide antigens, such as 23-valent pneumococcal polysaccharide vaccine (PPV), meningococcal, isohaemagglutinins and more recently Salmonella typhi Vi polysaccharide vaccine (TV) The latter has been suggested as a complementary approach when interpretation of gold standard test (PPV) might be challenging [8,9,10,11,12]
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