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在 SARS-CoV-2 潘多拉大流行中:通过粪便 Adnab-9 与 p87:血转铁蛋白的结合来衡量的预存肠道先天免疫系统的状态,能否预测前瞻性人群数据库中 COVID-19 的易感性和存活率?

In the SARS-CoV-2 Pandora Pandemic: Can the Stance of Premorbid Intestinal Innate Immune System as Measured by Fecal Adnab-9 Binding of p87:Blood Ferritin, Yielding the FERAD Ratio, Predict COVID-19 Susceptibility and Survival in a Prospective Population Database?

机构信息

Research and Development Service, Detroit VAMC, 4747 John R Street, Detroit, MI 48602, USA.

Blood Transfusion and Donor Services, Department of Pathology, Maimonides Medical Center, 4802 10th Avenue, Brooklyn, NY 11219, USA.

出版信息

Int J Mol Sci. 2023 Apr 19;24(8):7536. doi: 10.3390/ijms24087536.

Abstract

SARS-CoV-2 severity predictions are feasible, though individual susceptibility is not. The latter prediction allows for planning vaccination strategies and the quarantine of vulnerable targets. Ironically, the innate immune response (InImS) is both an antiviral defense and the potential cause of adverse immune outcomes. The competition for iron has been recognized between both the immune system and invading pathogens and expressed in a ratio of ferritin divided by p87 (as defined by the Adnab-9 ELISA stool-binding optical density, minus the background), known as the FERAD ratio. Associations with the FERAD ratio may allow predictive modeling for the susceptibility and severity of disease. We evaluated other potential COVID-19 biomarkers prospectively. Patients with PCR+ COVID-19 tests (Group 1; n = 28) were compared to three other groups. In Group 2 (n = 36), and 13 patients displayed COVID-19-like symptoms but had negative PCR or negative antibody tests. Group 3 (n = 90) had no symptoms and were negative when routinely PCR-tested before medical procedures. Group 4 (n = 2129) comprised a pool of patients who had stool tests and symptoms, but their COVID-19 diagnoses were unknown; therefore, they were chosen to represent the general population. Twenty percent of the Group 4 patients (n = 432) had sufficient data to calculate their FERAD ratios, which were inversely correlated with the risk of COVID-19 in the future. In a case report of a neonate, we studied three biomarkers implicated in COVID-19, including p87, Src (cellular-p60-sarcoma antigen), and Abl (ABL-proto-oncogene 2). The InImS of the first two were positively correlated. An inverse correlation was found between ferritin and lysozyme in serum ( < 0.05), suggesting that iron could have impaired an important innate immune system anti-viral effector and could partially explain future COVID-19 susceptibility.

摘要

SARS-CoV-2 严重程度的预测是可行的,尽管个体易感性是不可预测的。后者的预测允许制定疫苗接种策略和隔离脆弱目标。具有讽刺意味的是,先天免疫反应(InImS)既是抗病毒防御的潜在原因,也是不良免疫结果的潜在原因。免疫系统和入侵病原体之间已经认识到铁的竞争,并以铁蛋白除以 p87(由 Adnab-9 ELISA 粪便结合光密度定义,减去背景)的比值表示,称为 FERAD 比值。与 FERAD 比值相关联可能允许对疾病的易感性和严重程度进行预测建模。我们前瞻性地评估了其他潜在的 COVID-19 生物标志物。与三组患者相比,PCR+ COVID-19 检测患者(第 1 组;n = 28)。在第 2 组(n = 36)中,有 13 例患者出现 COVID-19 样症状,但 PCR 或抗体检测均为阴性。第 3 组(n = 90)在接受医疗程序前常规进行 PCR 检测时无症状且呈阴性。第 4 组(n = 2129)由一组接受粪便检查和症状但 COVID-19 诊断未知的患者组成;因此,他们被选择代表一般人群。第 4 组患者中有 20%(n = 432)有足够的数据来计算他们的 FERAD 比值,这些比值与未来 COVID-19 的风险呈反比。在对一名新生儿的病例报告中,我们研究了与 COVID-19 相关的三个生物标志物,包括 p87、Src(细胞-p60-肉瘤抗原)和 Abl(ABL-原癌基因 2)。前两个的先天免疫反应呈正相关。在血清中发现铁蛋白和溶菌酶之间呈负相关(<0.05),表明铁可能损害了重要的先天免疫系统抗病毒效应物,并部分解释了未来 COVID-19 的易感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ea/10145175/76f9e2e30bd7/ijms-24-07536-g001.jpg

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