Identification of Potential Biomarkers in Peripheral Blood Supernatants of South African Patients with Syphilitic and Herpetic Uveitis.

Purpose: To identify potential diagnostic biomarkers for herpetic and syphilitic uveitis.Methods: Blood samples were collected from 92 uveitis patients. Concentrations of 47 biomarkers were evaluated in unstimulated Quantiferon supernatants using the Luminex platform.Results: Results showed 11 patients (12%) had herpetic uveitis, 11 (12%) syphilis, 40 (43.5%) other infectious causes, 16 (17.4%) established noninfectious causes and 14 (15.2%) were idiopathic. Biomarker analysis revealed three proteins (Apo-A1, Apo-CIII, CRP) that differed between syphilis and other causes. A three-marker biosignature (CCL4/MIP-1ß, Apo-CIII and CRP) separated syphilis from other groups with AUC = 0.83 (95% CI: 0.68-0.98). Apo-CIII and CRP differed between herpetic cases and other groups (p < .05). A three-analyte biosignature (Apo-A1, SAP and CRP) separated the herpetic group from other groups with AUC = 0.79 (95% CI: 0.65-0.93).Conclusion: We have identified candidate biomarkers with potential to differentiate between herpetic, syphilitic and other causes of uveitis. These results warrant further investigation in larger future studies.

Evaluation of Potential Antigen-specific Host Biomarkers in QuantiFERON Supernatants as Candidates for the Diagnosis of Ocular Tuberculosis.

Purpose: To evaluate potential host biomarkers detectable in QuantiFERON supernatants as diagnostic candidates for ocular tuberculosis (OTB).Methods: We investigated 47 host markers in QuantiFERON supernatants from 92 individuals with uveitis using the Luminex platform. We evaluated the potential of individual and combined biomarkers to distinguish between patients with possible, probable, and no OTB.Results: Differences were observed in median concentrations of several biomarkers including IL-13, IFN-γ, IFN-α2, and IL-1ß, in individuals with OTB versus no OTB regardless of HIV status. Individuals with probable and possible OTB only differed regarding GM-CSF. We identified a four-marker biosignature (CD40 L, IL-33, IFN-γ, and SAP) which diagnosed OTB with an area under the ROC curve of 0.80, sensitivity = 56.3% and specificity = 90.0%.Conclusion: This represents the first attempt at screening QuantiFERON supernatants for biomarkers to diagnose OTB. We identified candidate biosignatures which may aid in diagnosing OTB in both HIV positive and negative patients.

Prospective evaluation of host biomarkers other than interferon gamma in QuantiFERON Plus supernatants as candidates for the diagnosis of tuberculosis in symptomatic individuals.

BACKGROUND: There is an urgent need for new tools for the diagnosis of TB. We evaluated the usefulness recently described host biomarkers in supernatants from the newest generation of the QuantiFERON test (QuantiFERON Plus) as tools for the diagnosis of active TB. METHODS: We recruited individuals presenting at primary health care clinics in Cape Town, South Africa with symptoms requiring investigation for TB disease, prior to the establishment of a clinical diagnosis. Participants were later classified as TB or other respiratory diseases (ORD) based on the results of clinical and laboratory tests. Using a multiplex platform, we evaluated the concentrations of 37 host biomarkers in QuantiFERON Plus supernatants from study participants as tools for the diagnosis of TB. RESULTS: Out of 120 study participants, 35(29.2%) were diagnosed with active TB, 69(57.5%) with ORD whereas 16(13.3%) were excluded. 14(11.6%) of the study participants were HIV infected. Although individual host markers showed potential as diagnostic candidates, the main finding of the study was the identification of a six-marker biosignature in unstimulated supernatants (Apo-ACIII, CXCL1, CXCL9, CCL8, CCL-1, CD56) which diagnosed TB with sensitivity and specificity of 73.9%(95% CI; 51.6-87.8) and 87.6%(95% CI; 77.2-94.5), respectively, after leave-one-out cross validation. Combinations between TB-antigen specific biomarkers also showed potential (sensitivity of 77.3% and specificity of 69.2%, respectively), with multiple biomarkers being significantly different between TB patients, Quantiferon Plus Positive and Quantiferon Plus negative individuals with ORD, regardless of HIV status. CONCLUSIONS: Biomarkers detected in QuantiFERON Plus supernatants may contribute to adjunctive diagnosis of TB.