Unbiased discovery of autoantibodies associated with severe COVID-19 via genome-scale self-assembled DNA-barcoded protein libraries.

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.

• Authors: Joel J Credle, Jonathan Gunn, Puwanat Sangkhapreecha, Daniel R Monaco, Xuwen Alice Zheng, Hung-Ji Tsai, Azaan Wilbon, William R Morgenlander, Andre Rastegar, Yi Dong, Sahana Jayaraman, Lorenzo Tosi, Biju Parekkadan, Alan N Baer, Mario Roederer, Evan M Bloch, Aaron A R Tobian, Israel Zyskind, Jonathan I Silverberg, Avi Z Rosenberg, Andrea L Cox, Tom Lloyd, Andrew L Mammen, H Benjamin Larman
• Journal: Nature biomedical engineering (Nat Biomed Eng) Vol. 6 Issue 8 Pg. 992-1003 (08 2022) ISSN: 2157-846X [Electronic] England
• PMID: 35986181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• Autoantibodies
• Interferon-alpha

Topics

• Autoantibodies
• COVID-19 (therapy)
• Gene Library
• Humans
• Immunization, Passive
• Interferon-alpha
• COVID-19 Serotherapy