当前位置: X-MOL 学术Nat. Biomed. Eng. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Unbiased discovery of autoantibodies associated with severe COVID-19 via genome-scale self-assembled DNA-barcoded protein libraries
Nature Biomedical Engineering ( IF 26.8 ) Pub Date : 2022-08-19 , DOI: 10.1038/s41551-022-00925-y
Joel J Credle 1 , Jonathan Gunn 1 , Puwanat Sangkhapreecha 1 , Daniel R Monaco 1 , Xuwen Alice Zheng 1 , Hung-Ji Tsai 2 , Azaan Wilbon 1 , William R Morgenlander 1 , Andre Rastegar 1 , Yi Dong 3 , Sahana Jayaraman 1 , Lorenzo Tosi 4 , Biju Parekkadan 4 , Alan N Baer 5 , Mario Roederer 6 , Evan M Bloch 7 , Aaron A R Tobian 7 , Israel Zyskind 8, 9 , Jonathan I Silverberg 10 , Avi Z Rosenberg 11 , Andrea L Cox 12 , Tom Lloyd 13, 14 , Andrew L Mammen 13, 15, 16 , H Benjamin Larman 1
Affiliation  

Pathogenic autoreactive antibodies that may be associated with life-threatening coronavirus disease 2019 (COVID-19) remain to be identified. Here, we show that self-assembled genome-scale libraries of full-length proteins covalently coupled to unique DNA barcodes for analysis by sequencing can be used for the unbiased identification of autoreactive antibodies in plasma samples. By screening 11,076 DNA-barcoded proteins expressed from a sequence-verified human ORFeome library, the method, which we named MIPSA (for Molecular Indexing of Proteins by Self-Assembly), allowed us to detect circulating neutralizing type-I and type-III interferon (IFN) autoantibodies in five plasma samples from 55 patients with life-threatening COVID-19. In addition to identifying neutralizing type-I IFN-α and IFN-ω autoantibodies and other previously known autoreactive antibodies in patient plasma, MIPSA enabled the detection of as yet unidentified neutralizing type-III anti-IFN-λ3 autoantibodies that were not seen in healthy plasma samples or in convalescent plasma from ten non-hospitalized individuals with COVID-19. The low cost and simple workflow of MIPSA will facilitate unbiased high-throughput analyses of protein–antibody, protein–protein and protein–small-molecule interactions.



中文翻译:


通过基因组规模自组装 DNA 条形码蛋白库公正地发现与严重 COVID-19 相关的自身抗体



可能与危及生命的 2019 年冠状病毒病 (COVID-19) 相关的致病性自身反应抗体仍有待鉴定。在这里,我们展示了与独特的 DNA 条形码共价偶联的全长蛋白质的自组装基因组规模文库,用于测序分析,可用于血浆样品中自身反应抗体的公正鉴定。通过筛选从序列验证的人类 ORFeome 文库中表达的 11,076 个 DNA 条形码蛋白质,我们将这种方法命名为 MIPSA(自组装蛋白质分子索引),使我们能够检测循环中和性 I 型和 III 型干扰素(IFN) 自身抗体来自 55 名危及生命的 COVID-19 患者的 5 份血浆样本。除了鉴定患者血浆中的中和性 I 型 IFN-α 和 IFN-ω 自身抗体以及其他先前已知的自身反应性抗体外,MIPSA 还能够检测到尚未鉴定的中和性 III 型抗 IFN-λ3 自身抗体,这些抗体在健康人中未见。来自 10 名未住院的 COVID-19 患者的血浆样本或恢复期血浆。 MIPSA 的低成本和简单的工作流程将有助于对蛋白质-抗体、蛋白质-蛋白质和蛋白质-小分子相互作用进行公正的高通量分析。

更新日期:2022-08-19
down
wechat
bug