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

Abstract

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.

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

“…Given the lack of a reliable anti-typhi Vi IgG standardization, several studies have measured the pre- and post-vaccination concentration ratio, demonstrating a median 3-fold increase in more than 95% of the cohorts (14, 15). Similarly, the utility of evaluation for humoral immune response patients with PID was shown in recent studies (2, 3, 8, 10, 13).…”

“…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.…”

“…A meta-analysis of anti-pneumococcal antibody responses on an individual serotype basis in healthy individuals showed that the ratios of pre- and post-vaccination titters varied widely and depended on the particular antibody serotype and baseline levels [4]. There is not a clear consensus from laboratories between the measurement and importance of each individual serotype response and the total value of the pneumococcal polysaccharide IgG vaccine (3, 8–10). Likewise, the assessment of each specific serotype requires a single ELISA, which is time-consuming and expensive to be applied in the routine practice and is therefore available at only a few highly qualified laboratories in Spain for research purposes (8).…”

Overview of antibody‐mediated immunity to S. pneumoniae: pneumococcal infections, pneumococcal immunity assessment, and recommendations for IG product evaluation

“…The antigen in this assay is the 23-valent vaccine or a commercially available enzyme immunoassay kit. 28 Results in the normal range for this test can be due to antibodies to most or all included serotypes or by high antibodies to only one serotype. Serotype-specific antibody concentrations are needed for an accurate assessment of antibody-mediated immunity to S. pneumoniae.…”

“…While most tests of anti‐pneumococcal IgG antibodies measure specific anti‐serotype antibodies individually, in many places a global ELISA test that measures antibodies against all 23 serotypes present in the 23‐valent vaccine simultaneously is preferred because of its simplicity and low cost. The antigen in this assay is the 23‐valent vaccine or a commercially available enzyme immunoassay kit . Results in the normal range for this test can be due to antibodies to most or all included serotypes or by high antibodies to only one serotype.…”