Tuberculosis (TB) patients present dysregulated immunity, iron metabolism and anaemia of inflammation. In this study, circulatory cytokines, trace metals, and iron-related proteins (hepcidin, ferroportin, transferrin, DMT1, Nramp1, ferritin, ceruloplasmin, hemojuvelin, aconitase, transferring receptor) were monitored in case (active tuberculosis patients: ATB) and control (non-tuberculosis: NTB and healthy) study populations (n=72, male, 42.94 mean age (16-83)). Using serum elemental and cytokine levels, a partial least square discriminate analysis model (PLS-DA) was built and variables with a VIP score of >0.6 were selected as important markers. A biosignature of IL-13, IL-12(p70), IFN-γ, IL-10, IL-5, IL-18, IL-4, Selenium, and Aluminium clustered ATB away from controls. Interestingly, low iron and selenium levels, while high copper and aluminum levels were observed in ATB subjects. All the important serum cytokines were positively correlated in ATB subjects. A low abundance of transferrin, ferroportin, and hemojuvelin, while higher ferritin and ceruloplasmin levels explained an altered iron metabolism in ATB subjects which partially resolved upon completion of treatment. Further, the identified biosignature in TB patients, that explained anemia of inflammation, along with perturbed iron homeostasis could be useful targets for the development of host-directed adjunct therapeutics.

中文翻译：

---

低水平的铁和硒与高 IL-6/IL-10 可能影响结核病患者的营养免疫

结核病 (TB) 患者表现出免疫失调、铁代谢和炎症性贫血。在本研究中，在病例（活动性结核病患者：ATB）和对照中监测循环细胞因子、微量金属和铁相关蛋白（铁调素、转运蛋白、转铁蛋白、DMT1、Nramp1、铁蛋白、铜蓝蛋白、血幼蛋白、乌头酸酶、转移受体） （非结核病：NTB 和健康）研究人群（n=72，男性，平均年龄 42.94 (16-83)）。使用血清元素和细胞因子水平，建立偏最小二乘判别分析模型（PLS-DA），并选择VIP评分>0.6的变量作为重要标志物。IL-13、IL-12(p70)、IFN-γ、IL-10、IL-5、IL-18、IL-4、硒和铝的生物特征使 ATB 远离对照。有趣的是，低铁和硒水平，而在 ATB 受试者中观察到高铜和铝水平。所有重要的血清细胞因子在 ATB 受试者中均呈正相关。低丰度的转铁蛋白、铁转运蛋白和血幼蛋白，而较高的铁蛋白和铜蓝蛋白水平解释了 ATB 受试者中铁代谢的改变，这在治疗完成后部分解决。此外，在结核病患者中确定的生物印记可以解释炎症性贫血以及铁稳态紊乱，这可能是开发宿主导向的辅助疗法的有用目标。而较高的铁蛋白和铜蓝蛋白水平解释了 ATB 受试者中铁代谢的改变，这在治疗完成后部分解决。此外，在结核病患者中确定的生物印记可以解释炎症性贫血以及铁稳态紊乱，这可能是开发宿主导向的辅助疗法的有用目标。而较高的铁蛋白和铜蓝蛋白水平解释了 ATB 受试者中铁代谢的改变，这在治疗完成后部分解决。此外，在结核病患者中鉴定出的生物印记可以解释炎症性贫血以及铁稳态紊乱，这可能是开发宿主导向的辅助疗法的有用目标。