Postdoctoral Researcher Postgraduate Program in Health Sciences School of Medicine, Pontifícia Universidade Católica do Paraná - PUCPR, Curitiba, PR, Brazil.
Postgraduate Program of Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná - PUCPR, Curitiba, PR, Brazil.
Transl Res. 2021 May;231:55-63. doi: 10.1016/j.trsl.2020.11.008. Epub 2020 Nov 20.
Although some evidence showed the activation of complement systems in COVID-19 patients, proinflammatory status and lectin pathway remain unclear. Thus, the present study aimed to demonstrate the role of MBL and ficolin-3 in the complement system activation and compared to pandemic Influenza A virus H1N1 subtype infection (H1N1pdm09) and control patients. A total of 27 lungs formalin-fixed paraffin-embedded samples (10 from H1N1 group, 6 from the COVID-19 group, and 11 from the control group) were analyzed by immunohistochemistry using anti-IL-6, TNF-alfa, CD163, MBL e FCN3 antibodies. Genotyping of target polymorphisms in the MBL2 gene was performed by real-time PCR. Proinflammatory cytokines such as IL-6 and TNF-alpha presented higher tissue expression in the COVID-19 group compared to H1N1 and control groups. The same results were observed for ICAM-1 tissue expression. Increased expression of the FCN3 was observed in the COVID-19 group and H1N1 group compared to the control group. The MBL tissue expression was higher in the COVID-19 group compared to H1N1 and control groups. The genotypes AA for rs180040 (G/A), GG for rs1800451 (G/A) and CC for rs5030737 (T/C) showed a higher prevalence in the COVID-19 group. The intense activation of the lectin pathway, with particular emphasis on the MBL pathway, together with endothelial dysfunction and a massive proinflammatory cytokines production, possibly lead to a worse outcome in patients infected with SARS-Cov-2. Moreover, 3 SNPs of our study presented genotypes that might be correlated with high MBL tissue expression in the COVID-19 pulmonary samples.
尽管一些证据表明 COVID-19 患者的补体系统被激活,但炎症状态和凝集素途径仍不清楚。因此,本研究旨在展示 MBL 和 ficolin-3 在补体系统激活中的作用,并与大流行性流感 A 病毒 H1N1 亚型感染(H1N1pdm09)和对照组患者进行比较。总共分析了 27 个福尔马林固定石蜡包埋的肺组织样本(10 个来自 H1N1 组,6 个来自 COVID-19 组,11 个来自对照组),使用抗 IL-6、TNF-alfa、CD163、MBL 和 FCN3 抗体进行免疫组织化学染色。通过实时 PCR 对 MBL2 基因的目标多态性进行基因分型。与 H1N1 和对照组相比,COVID-19 组的组织中促炎细胞因子如 IL-6 和 TNF-alfa 的表达更高。ICAM-1 组织表达也观察到相同的结果。与对照组相比,COVID-19 组和 H1N1 组的 FCN3 表达增加。与 H1N1 和对照组相比,COVID-19 组的 MBL 组织表达更高。COVID-19 组的 rs180040(G/A)的 AA 基因型、rs1800451(G/A)的 GG 基因型和 rs5030737(T/C)的 CC 基因型更为常见。凝集素途径的强烈激活,特别是 MBL 途径,加上内皮功能障碍和大量促炎细胞因子的产生,可能导致感染 SARS-CoV-2 的患者预后更差。此外,我们研究的 3 个 SNP 显示出的基因型可能与 COVID-19 肺部样本中高 MBL 组织表达相关。