Centre for International Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
Proteomics Unit at University of Bergen (PROBE), Department of Biomedicine, University of Bergen, Bergen, Norway.
PLoS One. 2023 Feb 14;18(2):e0281757. doi: 10.1371/journal.pone.0281757. eCollection 2023.
This study aimed at exploring the proteomic profile of PBMCs to predict treatment response in pulmonary tuberculosis (PTB). This was a pilot study conducted among 8 adult patients from Zanzibar, Tanzania with confirmed PTB. Blood samples were collected at baseline, at 2 months of treatment, and at the end of treatment at 6 months. Proteins were extracted from PBMCs and analyzed using LC-MS/MS based label free quantitative proteomics. Overall, 3,530 proteins were quantified across the samples, and 12 differentially expressed proteins were identified at both 2 months of treatment and at treatment completion, which were involved in cellular and metabolic processes, as well as binding and catalytic activity. Seven were downregulated proteins (HSPA1B/HSPA1A, HSPH1, HSP90AA1, lipopolysaccharide-binding protein, complement component 9, calcyclin-binding protein, and protein transport protein Sec31A), and 5 proteins were upregulated (SEC14 domain and spectrin repeat-containing protein 1, leucine-rich repeat-containing 8 VRAC subunit D, homogentisate 1,2-dioxygenase, NEDD8-activating enzyme E1 regulatory subunit, and N-acetylserotonin O-methyltransferase-like protein). The results showed that proteome analysis of PBMCs can be used as a novel technique to identify protein abundance change with anti-tuberculosis treatment. The novel proteins elucidated in this work may provide new insights for understanding PTB pathogenesis, treatment, and prognosis.
本研究旨在探索 PBMC 的蛋白质组谱,以预测肺结核(PTB)的治疗反应。这是在坦桑尼亚桑给巴尔的 8 名成年确诊肺结核患者中进行的一项试点研究。在基线、治疗 2 个月和治疗 6 个月结束时采集血样。从 PBMC 中提取蛋白质,并使用基于 LC-MS/MS 的无标记定量蛋白质组学进行分析。总体而言,在所有样本中定量了 3530 种蛋白质,在治疗 2 个月和治疗结束时鉴定出 12 种差异表达的蛋白质,这些蛋白质参与细胞和代谢过程以及结合和催化活性。其中有 7 种下调蛋白(HSPA1B/HSPA1A、HSPH1、HSP90AA1、脂多糖结合蛋白、补体成分 9、钙调蛋白结合蛋白和蛋白质转运蛋白 Sec31A),5 种上调蛋白(SEC14 结构域和富含螺旋重复的蛋白 1、富含亮氨酸重复的 8 VRAC 亚基 D、高丝氨酸 1,2-二加氧酶、NEDD8-激活酶 E1 调节亚基和 N-乙酰丝氨酸 O-甲基转移酶样蛋白)。结果表明,PBMC 的蛋白质组分析可用作一种新的技术,以鉴定抗结核治疗中蛋白质丰度的变化。本工作中阐明的新蛋白质可能为理解肺结核的发病机制、治疗和预后提供新的见解。