Anti-Treponema pallidum IgA response as a potential diagnostic marker of syphilis

Serological tests for syphilis detect mainly total Ig, IgM or IgG antibodies. We aimed to evaluate the specific IgA response in syphilis patients according to disease stage.

A serum IgA-enzyme immunoassay was developed using commercially available microplates coated with recombinant treponemal antigens and an anti-IgA-conjugate. To define a cut-off, we used 91 syphilis positive and 136 negative sera previously defined by the rapid plasma reagin and the Treponema pallidum particle agglutination results. Then we determined the intra- and inter-assay precisions, diagnostic sensitivity according to the clinical stage (in 66, 55 and 42 sera from primary, secondary and latent syphilis patients, respectively) and specificity (in 211 sera from people with conditions different to syphilis). IgA values were further measured in 71 sera from patients with previously treated syphilis.

The newly developed IgA-enzyme immunoassay showed a good discrimination between negative and positive samples with intra- and inter-assay variation coefficients <20%. The sensitivity was 80.3% (95% CI, 70.0-90.6), 100.0% (95% CI, 99.1-100.0) and 95.2% (95% CI, 87.6-100.0) in primary, secondary and latent syphilis, respectively, and the specificity was 98.1% (95% CI, 96.0-100.0). Further, IgA values were negative in 61.3% (38/62) of patients with previously treated syphilis.

Our findings suggest serum IgA as a sensitive and specific marker of syphilis and its detection could be used as a screening assay for active infection. Further evaluation is needed in prospective longitudinal field studies.