School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
Auckland Science Analytical Services, The University of Auckland, Auckland, New Zealand.
Immun Inflamm Dis. 2021 Mar;9(1):90-107. doi: 10.1002/iid3.349. Epub 2020 Nov 21.
The pathophysiology and temporal dynamics of affected tissues in chronic rhinosinusitis (CRS) remain poorly understood. Here, we present a multiomics-based time-series assessment of nasal polyp biopsies from three patients with CRS, assessing natural variability over time and local response to systemic corticosteroid therapy.
Polyp tissue biopsies were collected at three time points over two consecutive weeks. Patients were prescribed prednisone (30 mg daily) for 1 week between Collections 2 and 3. Polyp transcriptome, proteome, and microbiota were assessed via RNAseq, SWATH mass spectrometry, and 16S ribosomal RNA and ITS2 amplicon sequencing. Baseline interpatient variability, natural intrapatient variability over time, and local response to systemic corticosteroids, were investigated.
Overall, the highly abundant transcripts and proteins were associated with pathways involved in inflammation, FAS, cadherin, integrin, Wnt, apoptosis, and cytoskeletal signaling, as well as coagulation and B- and T-cell activation. Transcripts and proteins that naturally varied over time included those involved with inflammation- and epithelial-mesenchymal transition-related pathways, and a number of common candidate target biomarkers of CRS. Ten transcripts responded significantly to corticosteroid therapy, including downregulation of TNF, CCL20, and GSDMA, and upregulation of OVGP1, and PCDHGB1. Members of the bacterial genus Streptococcus positively correlated with immunoglobulin proteins IGKC and IGHG1.
Understanding natural dynamics of CRS-associated tissues is essential to provide baseline context for all studies on putative biomarkers, mechanisms, and subtypes of CRS. These data further our understanding of the natural dynamics within nasal polypoid tissue, as well as local changes in response to systemic corticosteroid therapy.
慢性鼻-鼻窦炎（CRS）患者受影响组织的病理生理学和时变动力学仍知之甚少。在此，我们通过对 3 例 CRS 患者的鼻息肉活检组织进行基于多组学的时间序列评估，研究了组织的自然时变和对全身皮质类固醇治疗的局部反应。
在连续 2 周的时间内，在 3 个时间点采集息肉组织活检。在第 2 次和第 3 次采集之间的 1 周内，患者被开具泼尼松（30mg/d）处方。通过 RNA-seq、SWATH 质谱分析和 16S rRNA 和 ITS2 扩增子测序，评估息肉转录组、蛋白质组和微生物组。研究了基线患者间变异性、随时间的自然患者内变异性，以及全身皮质类固醇的局部反应。
总体而言，高度丰富的转录本和蛋白质与涉及炎症、FAS、钙粘蛋白、整合素、Wnt、凋亡和细胞骨架信号传导以及凝血和 B 和 T 细胞激活的途径有关。随时间自然变化的转录本和蛋白质包括与炎症和上皮-间充质转化相关途径相关的转录本和蛋白质，以及许多 CRS 的常见候选治疗靶点生物标志物。10 个转录本对皮质类固醇治疗有显著反应，包括 TNF、CCL20 和 GSDMA 的下调，以及 OVGP1 和 PCDHGB1 的上调。细菌属链球菌的成员与免疫球蛋白蛋白 IGKC 和 IGHG1 呈正相关。
了解 CRS 相关组织的自然动态对于所有关于潜在生物标志物、机制和 CRS 亚型的研究提供基线背景至关重要。这些数据进一步加深了我们对鼻息肉组织内自然动态以及对全身皮质类固醇治疗的局部变化的理解。
