Abstract
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.
【초록키워드】 COVID-19, convalescent plasma, Sequencing, interferon, Protein, DNA, Patient, IFN, plasma, Neutralizing, interactions, Analysis, IFN-α, autoantibody, life-threatening coronavirus disease, plasma samples, life-threatening, circulating, FIVE, plasma sample, full-length protein, detect, healthy, addition, facilitate, can be used, unique, expressed, ORFeome, autoreactive antibody, individuals with COVID-19, 【제목키워드】 severe COVID-19, Protein, autoantibody,