Mutavhatsindi Hygon, Du Bruyn Elsa, Ruzive Sheena, Howlett Patrick, Cerrone Maddalena, Sher Alan, Mayer-Barber Katrin D, Barber Daniel L, Ntsekhe Mpiko, Wilkinson Robert J, Riou Catherine
Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, South Africa.
Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory, South Africa.
Open Forum Infect Dis. 2023 Mar 9;10(3):ofad128. doi: 10.1093/ofid/ofad128. eCollection 2023 Mar.
To better understand the pathogenesis of pericardial tuberculosis (PCTB), we sought to characterize the systemic inflammatory profile in people with human immunodeficiency virus type 1 (HIV-1) with latent TB infection (LTBI), pulmonary TB (PTB), or PCTB.
Using Luminex, we measured the concentration of 39 analytes in pericardial fluid (PCF) and paired plasma from 18 PCTB participants, and plasma from 16 LTBI and 20 PTB participants. Follow-up plasma samples were also obtained from PTB and PCTB participants. HLA-DR expression on -specific CD4 T cells was measured in baseline samples using flow cytometry.
Assessment of the overall systemic inflammatory profile by principal component analysis showed that the inflammatory profile of active TB participants was distinct from the LTBI group, while PTB patients could not be distinguished from those with PCTB. When comparing the inflammatory profile between PCF and paired blood, we found that the concentrations of most analytes (25/39) were elevated at site of disease. However, the inflammatory profile in PCF partially mirrored inflammatory events in the blood. After TB treatment completion, the overall plasma inflammatory profile reverted to that observed in the LTBI group. Lastly, HLA-DR expression showed the best performance for TB diagnosis compared to previously described biosignatures built from soluble markers.
Our results show that the inflammatory profile in blood was comparable between PTB and PCTB. However, at the site of infection (PCF), inflammation was significantly elevated compared to blood. Additionally, our data emphasize the potential role of HLA-DR expression as a biomarker for TB diagnosis.
为了更好地理解心包结核（PCTB）的发病机制，我们试图描述1型人类免疫缺陷病毒（HIV-1）感染者合并潜伏性结核感染（LTBI）、肺结核（PTB）或PCTB时的全身炎症特征。
我们使用Luminex技术检测了18例PCTB参与者的心包积液（PCF）和配对血浆以及16例LTBI参与者和20例PTB参与者血浆中39种分析物的浓度。还从PTB和PCTB参与者处获取了随访血浆样本。使用流式细胞术在基线样本中测量特异性CD4 T细胞上的HLA-DR表达。
通过主成分分析评估整体全身炎症特征表明，活动性结核参与者的炎症特征与LTBI组不同，而PTB患者与PCTB患者无法区分。比较PCF和配对血液中的炎症特征时，我们发现大多数分析物（25/39）在疾病部位浓度升高。然而，PCF中的炎症特征部分反映了血液中的炎症事件。结核治疗完成后，整体血浆炎症特征恢复到LTBI组观察到的水平。最后，与先前描述的由可溶性标志物构建的生物标志物相比，HLA-DR表达在结核诊断中表现最佳。
我们的结果表明，PTB和PCTB患者血液中的炎症特征相当。然而，在感染部位（PCF），炎症比血液中显著升高。此外，我们的数据强调了HLA-DR表达作为结核诊断生物标志物的潜在作用。
