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

Front Immunol. 2017 Dec 20;8:1862. doi: 10.3389/fimmu.2017.01862. eCollection 2017.

Abstract

Background: An 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).

Objective: To evaluate the OVA relative to the reference SSA.

Methods: Serum 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.

Results: Sixty-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.

Conclusion: A 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.

Keywords: humoral immunodeficiency; overall assay; pneumococcal polysaccharide response; polysaccharide response; primary immunodeficiency; serotype-specific assay.