Antibody responses to protein A in patients with Staphylococcus aureus bacteremia and endocarditis

To assess the significance of antibody to Staphylococcus aureus protein A (SpA) in human sera, we developed a modified enzyme-linked immunosorbent assay (ELISA). SpA antibody levels in 23 patients with S. aureus endocarditis (IE), 21 patients with non-IE S. aureus bacteremia, and 33 controls were measured. Geometric mean levels of antibody to SpA were significantly higher in S. aureus IE patients (134 ELISA units [EU]) than in uninfected controls (52 EU; P less than 0.01). Also, a significantly greater proportion of S. aureus IE patients (12 of 23) and S. aureus non-IE bacteremia patients (11 of 21) had antibody levels greater than an arbitrary threshold of 100 EU compared with uninfected controls (0 of 23; P less than or equal to 0.001). However, no significant differences in geometric mean SpA antibody levels between the bacteremic patients with and without IE were noted. The sensitivity and specificity of this ELISA to distinguish patients with S. aureus IE from those with non-IE bacteremia were low (52 and 48%, respectively). There was a significant association between SpA antibody levels and either immunoglobulin G or immunoglobulin M teichoic acid antibody levels (r = 0.406, P less than 0.05; r = 0.571, P = 0.002, respectively). For patients from whom multiple sera were available (13 IE and 5 non-IE patients), SpA antibody levels were measured over time and showed a wide temporal variation of immune responses. We conclude that antibody responses to SpA can be measured in many patients with invasive S. aureus disease but that the levels are of insufficient sensitivity or specificity to be of clinical use as a diagnostic or prognostic test.