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

<b>Purpose</b>: To evaluate potential host biomarkers detectable in QuantiFERON supernatants as diagnostic candidates for ocular tuberculosis (OTB). <b>Methods</b>: 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. <b>Results</b>: Differences were observed in median concentrations of several biomarkers including IL-13, IFN-γ, IFN-α2, and IL-1β, 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%. <b>Conclusion</b>: 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.

**研究目的**：筛选可在γ干扰素释放试验（QuantiFERON）上清液中检出的宿主生物标志物，作为眼结核（ocular tuberculosis, OTB）的诊断候选标志物。
**研究方法**：本研究采用液相芯片（Luminex）平台，对92例葡萄膜炎患者的γ干扰素释放试验（QuantiFERON）上清液中的47种宿主标志物进行检测，评估单一及联合生物标志物区分可能、很可能以及无眼结核患者的能力。
**研究结果**：无论人类免疫缺陷病毒（HIV）感染状态如何，眼结核患者与无眼结核患者的多种生物标志物（包括白细胞介素-13（IL-13）、干扰素-γ（IFN-γ）、干扰素-α2（IFN-α2）及白细胞介素-1β（IL-1β））的中位数浓度存在显著差异。仅很可能与可能的眼结核患者的粒细胞-巨噬细胞集落刺激因子（GM-CSF）水平存在差异。本研究筛选得到由4种标志物组成的生物特征组合（CD40配体（CD40 L）、白细胞介素-33（IL-33）、干扰素-γ（IFN-γ）及信号淋巴细胞激活分子相关蛋白（SAP）），其诊断眼结核的受试者工作特征（ROC）曲线下面积为0.80，灵敏度为56.3%，特异度为90.0%。
**研究结论**：本研究首次尝试通过筛选γ干扰素释放试验（QuantiFERON）上清液中的生物标志物以诊断眼结核。本研究筛选得到的候选生物特征组合，可辅助诊断人类免疫缺陷病毒（HIV）阳性与阴性患者的眼结核。