Ethiopian Public Health Institute (EPHI), P.O.Box: 1242, Addis Ababa, Ethiopia.
Sci Rep. 2022 Jun 16;12(1):10133. doi: 10.1038/s41598-022-14305-8.
A comprehensive assessment of immunological profiles during HIV-TB co-infection is essential to predict mortality, and facilitate the development of effective diagnostic assays, therapeutic agents, and vaccines. Expression levels of 105 immune-related genes were measured at enrolment and 6th month follow-up from 9 deceased HIV and TB coinfected patients who died between 3 and 7th months follow-up and at enrolment, 6th and 18th month from 18 survived matched controls groups for 2 years. Focused gene expression profiling was assessed from peripheral whole blood using a dual-color Reverse-Transcription Multiplex Ligation-dependent Probe Amplification assay. Eleven of the 105 selected genes were differentially expressed between deceased individuals and survivor-matched controls at baseline. At baseline, IL4δ2 was significantly more highly expressed in the deceased group than survivor matched controls, whereas CD3E, IL7R, PTPRCv1, CCL4, GNLY, BCL2, CCL5, NOD1, TLR3, and NLRP13 had significantly lower expression levels in the deceased group compared to survivor matched controls. At baseline, a non-parametric receiver operator characteristic curve was conducted to determine the prediction of mortality of single genes identified CCL5, PTPRCv1, CD3E, and IL7R with Area under the Curve of 0.86, 0.86, 0.86, and 0.85 respectively. The expression of these genes in the survived control was increased at the end of TB treatment from that at baseline, while decreased in the deceased group. The expression of PTPRCv1, CD3E, CCL5, and IL7R host genes in peripheral blood of patients with TB-HIV coinfected can potentially be used as a predictor of mortality in the Ethiopian setting. Anti-TB treatment might be less likely to restore gene expression in the level expression of the deceased group. Therefore, other new therapeutics that can restore these genes (PTPRCv1, CD3E, IL7R, and CCL5) in the deceased groups at baseline might be needed to save lives.
对 HIV-TB 合并感染期间的免疫谱进行全面评估对于预测死亡率至关重要，并有助于开发有效的诊断检测、治疗药物和疫苗。从 9 名在随访 3 至 7 个月期间死亡的 HIV 和 TB 合并感染死亡患者以及 18 名匹配的存活对照者在入组、第 6 个月和第 18 个月的外周全血中测量了 105 个免疫相关基因的表达水平。使用双色逆转录多重连接依赖性探针扩增检测法评估了重点基因表达谱。在基线时，11 个选定基因在死亡个体与存活对照者之间存在差异表达。在基线时，与存活对照者相比，IL4δ2 在死亡组中显著高表达，而 CD3E、IL7R、PTPRCv1、CCL4、GNLY、BCL2、CCL5、NOD1、TLR3 和 NLRP13 在死亡组中的表达水平显著低于存活对照者。在基线时，进行了非参数接收者操作特征曲线分析，以确定识别的单个基因（CCL5、PTPRCv1、CD3E 和 IL7R）对死亡率的预测，曲线下面积分别为 0.86、0.86、0.86 和 0.85。在 TB 治疗结束时，存活对照者的这些基因表达增加，而死亡组则减少。在合并感染的 HIV-TB 患者的外周血中，PTPRCv1、CD3E、CCL5 和 IL7R 宿主基因的表达可能可用作埃塞俄比亚人群死亡率的预测指标。抗结核治疗可能不太可能恢复死亡组的基因表达水平。因此，可能需要其他新的治疗方法来恢复死亡组中这些基因（PTPRCv1、CD3E、IL7R 和 CCL5）在基线时的表达，以拯救生命。
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