Olsson Oskar, Björkman Per, Jansson Marianne, Balcha Taye Tolera, Mulleta Daba, Yeba Habtamu, Valfridsson Christine, Carlsson Fredric, Skogmar Sten
Department of Translational Medicine, Clinical Infection Medicine, Lund University, Malmö, Sweden.
Department of Laboratory Medicine, Division of Medical Microbiology, Lund University, Sweden.
Open Forum Infect Dis. 2019 Jan 31;6(2):ofz015. doi: 10.1093/ofid/ofz015. eCollection 2019 Feb.
Diagnosis of tuberculosis (TB) in human immunodeficiency virus (HIV)-coinfected individuals is challenging. We hypothesized that combinations of inflammatory markers could facilitate identification of active TB in HIV-positive individuals.
Participants were HIV-positive, treatment-naive adults systematically investigated for TB at Ethiopian health centers. Plasma samples from 130 subjects with TB (HIV/TB) and 130 subjects without TB (HIV/TB) were tested for concentration of the following markers: CCL5, C-reactive protein (CRP), interleukin (IL)-6, IL12-p70, IL-18, IL-27, interferon-γ-induced protein-10 (IP-10), procalcitonin (PCT), and soluble urokinase-type plasminogen activator receptor (suPAR). Analyzed markers were then assessed, either individually or in combination, with regard to infection status, CD4 cell count, and HIV ribonucleic acid (RNA) levels.
The HIV/TB subjects had higher levels of all markers, except IL12p70, compared with HIV/TB subjects. The CRP showed the best performance for TB identification (median 27.9 vs 1.8 mg/L for HIV/TB and HIV/TB, respectively; area under the curve [AUC]: 0.80). Performance was increased when CRP was combined with suPAR analysis (AUC, 0.83 [0.93 for subjects with CD4 cell count <200 cells/mm]). Irrespective of TB status, IP-10 concentrations correlated with HIV RNA levels, and both IP-10 and IL-18 were inversely correlated to CD4 cell counts.
Although CRP showed the best single marker discriminatory potential, combining CRP and suPAR analyses increased performance for TB identification.
在合并感染人类免疫缺陷病毒（HIV）的个体中诊断结核病（TB）具有挑战性。我们推测炎症标志物的组合有助于识别HIV阳性个体中的活动性结核病。
研究对象为在埃塞俄比亚健康中心接受系统性结核病调查的未接受过治疗的HIV阳性成年患者。对130例结核病患者（HIV/TB）和130例非结核病患者（HIV/TB）的血浆样本进行以下标志物浓度检测：趋化因子配体5（CCL5）、C反应蛋白（CRP）、白细胞介素（IL）-6、IL-12 p70、IL-18、IL-27、干扰素γ诱导蛋白10（IP-10）、降钙素原（PCT）和可溶性尿激酶型纤溶酶原激活物受体（suPAR）。然后分别或联合分析这些标志物在感染状态、CD4细胞计数和HIV核糖核酸（RNA）水平方面的情况。
与HIV/TB患者相比，HIV/TB患者除IL12 p70外，所有标志物水平均较高。CRP在结核病识别方面表现最佳（HIV/TB和HIV/TB患者的中位数分别为27.9和1.8 mg/L；曲线下面积[AUC]：0.80）。当CRP与suPAR分析联合时，性能有所提高（AUC为0.83[CD4细胞计数<200个细胞/mm的患者为0.93]）。无论结核病状态如何，IP-10浓度与HIV RNA水平相关，且IP-10和IL-18均与CD4细胞计数呈负相关。
尽管CRP显示出最佳的单一标志物鉴别潜力，但将CRP和suPAR分析联合可提高结核病识别性能。
