Treponema pallidum-specific immune responses and autoimmunity in patients who remain serofast after treatment of syphilis

Introduction
Approximately 15% of appropriately treated patients with early syphilis remain serofast. The pathogenesis and clinical significance of this phenomenon are unclear.

Aim
To determine the significance of Treponema pallidum-specific immune responses and autoimmunity in the treatment outcome of syphilis (serofast or proper serological response).

Material and Methods
Forty-eight patients with secondary and early latent syphilis (ELS) were enrolled in this study. Reactivity of IgM/IgG antibodies to the treponemal antigens TpN47, TpN17, TpN15 and TmpA was evaluated before and 12 months after intramuscular penicillin therapy for syphilis. Additionally, the presence of antinuclear antibodies (ANA) was determined 12 months after treatment.

Results
After 1 year, patients were stratified into two groups based on their serological response: (1) serofast (n = 10) and (2) serologically-cured (n = 38) patients. The serological cure rate was 79.2% at 12 months after treatment. Weak pre- and post-treatment antibody reactivity to TpN47 antigen was found to be significantly associated with a higher risk of the serofast state (OR = 64; 95% CI: 5.01–817; p < 0.005). Patients who remained serofast had a significantly higher ANA prevalence and mean titer when compared to those with proper serological responses (100% vs. 5.3%, respectively, p < 0.005; 1 : 640 vs. 1 : 160, respectively, p < 0.005).

Conclusions
We demonstrate that baseline antigen-specific immune response to Treponema pallidum may be an important predictor of the treatment outcome. Further studies are warranted to identify the role of autoimmunity in the pathomechanism of the serofast state.