Candidate Cytokine Biomarkers for the Diagnosis of Ocular- and Neurosyphilis.

Purpose: To describe differences in the expression of selected host biomarkers, by analysing the aqueous humour (AH), cerebrospinal fluid (CSF) and serum of patients with ocular syphilis, both with and without neurosyphilis and HIV infection, to support the diagnosis of ocular syphilis.

Methods: A prospective observational descriptive study was conducted at Tygerberg Academic Hospital in Cape Town, South Africa, from February 1, 2018, to January 31, 2021. The study included all patients aged 18 years or older who presented to the eye clinic with ocular syphilis, provided they had a positive serum Treponema pallidum antibodies (TPA) test, an RPR titre of ≥ 8 and confirmed ocular inflammation. The HIV status of each patient was determined and the CRP, IL-2, IL-6, IL-10, IL-12 p70, MIP-1$\beta$ and IFN-$\gamma$ were measured in their AH, CSF and serum samples using a multiplex immunoassay platform. All patients received treatment.

Results: The mean concentrations of biomarkers IL-2, IL-10, MIP-1$\beta$, IL-6, IL-12 p70 and IFN-$\gamma$ were consistently higher in the AH compared to the CSF and serum in patients with ocular syphilis, irrespective of their HIV status and the presence or absence of concurrent neurosyphilis.

Conclusion: Our findings showed significant differences in certain cytokine levels across the AH, CSF, and serum, with notably higher concentrations in the AH. This indicates that ocular syphilis triggers a unique immune response within the eye. As a result, further analysis of AH biomarkers is needed to determine if these may enhance the diagnosis of ocular and neurosyphilis.