@article{dd96d7ddbeea4818b5969c9261f90347,
title = "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.",
author = "Credle, {Joel J.} and Jonathan Gunn and Puwanat Sangkhapreecha and Monaco, {Daniel R.} and Zheng, {Xuwen Alice} and Tsai, {Hung Ji} and Azaan Wilbon and Morgenlander, {William R.} and Andre Rastegar and Yi Dong and Sahana Jayaraman and Lorenzo Tosi and Biju Parekkadan and Baer, {Alan N.} and Mario Roederer and Bloch, {Evan M.} and Tobian, {Aaron A.R.} and Israel Zyskind and Silverberg, {Jonathan I.} and Rosenberg, {Avi Z.} and Cox, {Andrea L.} and Tom Lloyd and Mammen, {Andrew L.} and {Benjamin Larman}, H.",
note = "Funding Information: This study was made possible by a Johns Hopkins University Provost Research Grant made through the Johns Hopkins COVID-19 Research Response Program, by a National Institute of General Medical Sciences (NIGMS) grant R01 GM127353 (to H.B.L. and B.P.), by a grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number K23HL151826 (to E.M.B.), by grants from the Sj{\"o}gren{\textquoteright}s Syndrome Foundation and the Jerome L. Greene Foundation (to A.N.B. and H.B.L.) and by funding from the intramural research programs of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. We thank S. Elledge for generously providing the human ORFeome library and the 90-aa human peptidome T7 phage display library. We thank R. Green, M. Catipovic, A. Buskirk, T. O{\textquoteright}Donnell, P. Duggal and J. Markle for helpful discussions. We also thank J. Franklin and the Johns Hopkins Synthesis and Sequencing Core for HPLC purification of the HaloLigand conjugated RT-primer, as well as L. Orzolek and H. Hao of the Johns Hopkins Transcriptomics and Deep Sequencing Core Facility. We also thank C. Tuckey at New England Biolabs for assistance with Translation kits. The severe COVID-19 specimens used for this work were part of the Johns Hopkins Biospecimen Repository, which relies on the contribution of many patients, research teams and clinicians. We thank the members of the NIH Vaccine Research Center for pre-pandemic sample collection: B. Graham, L. Novick, J. Casazza, J. Ledgerwood, U. Sarwar, L. Chang, C. Starr Hendel, L. Holman, S. Plummer, P. Costner, I. Gorden, B. Larkin, F. Mendoza, J. Saudners, K. Zephir, M. E. Enama, G. Yamshchikov, I. Pittman and P. Williams. Parts of some figures were created with BioRender.com. Funding Information: This study was made possible by a Johns Hopkins University Provost Research Grant made through the Johns Hopkins COVID-19 Research Response Program, by a National Institute of General Medical Sciences (NIGMS) grant R01 GM127353 (to H.B.L. and B.P.), by a grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number K23HL151826 (to E.M.B.), by grants from the Sj{\"o}gren{\textquoteright}s Syndrome Foundation and the Jerome L. Greene Foundation (to A.N.B. and H.B.L.) and by funding from the intramural research programs of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. We thank S. Elledge for generously providing the human ORFeome library and the 90-aa human peptidome T7 phage display library. We thank R. Green, M. Catipovic, A. Buskirk, T. O{\textquoteright}Donnell, P. Duggal and J. Markle for helpful discussions. We also thank J. Franklin and the Johns Hopkins Synthesis and Sequencing Core for HPLC purification of the HaloLigand conjugated RT-primer, as well as L. Orzolek and H. Hao of the Johns Hopkins Transcriptomics and Deep Sequencing Core Facility. We also thank C. Tuckey at New England Biolabs for assistance with Translation kits. The severe COVID-19 specimens used for this work were part of the Johns Hopkins Biospecimen Repository, which relies on the contribution of many patients, research teams and clinicians. We thank the members of the NIH Vaccine Research Center for pre-pandemic sample collection: B. Graham, L. Novick, J. Casazza, J. Ledgerwood, U. Sarwar, L. Chang, C. Starr Hendel, L. Holman, S. Plummer, P. Costner, I. Gorden, B. Larkin, F. Mendoza, J. Saudners, K. Zephir, M. E. Enama, G. Yamshchikov, I. Pittman and P. Williams. Parts of some figures were created with BioRender.com. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2022",
month = aug,
doi = "10.1038/s41551-022-00925-y",
language = "English (US)",
volume = "6",
pages = "992--1003",
journal = "Nature biomedical engineering",
issn = "2157-846X",
publisher = "Nature Publishing Group",
number = "8",
}