The immunological response to syphilis differs by HIV status; a prospective observational cohort study

Abstract

Background: It is not known if there is a difference in the immune response to syphilis between HIV-infected and uninfected individuals.

Methods: We prospectively recruited all patients with a new diagnosis of syphilis and tested their plasma for IFNα, IFNγ, IL-1β, IL-12p40, IL-12p70, IP-10, MCP-1, MIP-1α, MIP-1β, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10 and IL-17A at baseline pre-treatment and 6 months following therapy.

Results: A total of 79 HIV-infected [44 primary/secondary syphilis (PSS) and 35 latent syphilis (LS)] and 12 HIV-uninfected (10 PSS and 2 LS) cases of syphilis and 30 HIV-infected controls were included in the study. At the baseline visit, compared to the control group, concentrations of IL-10 were significantly elevated in the HIV-infected and uninfected groups. The level of IL-10 was significantly higher in the HIV-infected compared to the HIV-uninfected PSS group (25.3 pg/mL (IQR, 4.56-41.76) vs 2.73 pg/mL (IQR, 1.55-9.02), P = 0.0192). In the HIV-infected PSS group (but not the HIV-infected LS or HIV-uninfected PSS groups) the IP-10, MIP-1b, IL-6 and IL-8 were raised compared to the controls. IL-10 levels decreased but did not return to control baseline values by 6 months in HIV infected PSS and LS and HIV uninfected PSS.

Conclusion: PSS and LS in HIV-infected individuals is characterized by an increase in inflammatory and anti-inflammatory cytokines such as IL-10. The increase of IL-10 is greater in HIV-infected than uninfected individuals. Further work is required to ascertain if this is part of an immunological profile that correlates with adverse outcomes such as serofast syphilis and neurosyphilis, in HIV-infected individuals.

Keywords: HIV; IL-10; Immunology; Syphilis; Treponema pallidum.

Fig. 1

Plasma cytokine and chemokine concentrations in HIV-infected and uninfected patients with syphilis by syphilis stage at baseline and 6 month visit. Cytokine levels in each group (pg/ml, Y axis log scale) are shown as median and interquartile range (box), with 10th and 90th percentiles (whiskers). Letters (a) and (b) above the box-plot indicate statistically significant differences (P < 0.05) as compared with the HIV-infected controls and the comparison between HIV-infected and uninfected PSS groups, respectively. Abbreviations. PSS HIV+: Primary Secondary Syphilis HIV-infected, LS HIV+: Latent Syphilis HIV-infected, PSS HIV-: Primary Secondary Syphilis HIV-uninfected

Fig. 2

IL-10 response to primary and secondary syphilis infection in HIV-infected (solid lines) and uninfected individuals (dashed lines) at the time of infection (baseline visit) and at 6 months follow up (log scale)