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Neutralizing IFNL3 Autoantibodies in Severe COVID-19 Identified Using Molecular Indexing of Proteins by Self-Assembly
Joel J. Credle; Jonathan Gunn; Puwanat Sangkhapreecha; Daniel R. Monaco; Xuwen Alice Zheng; Hung-Ji Tsai; Azaan Wilbon; William R. Morgenlander; 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.
Affiliation
  • Joel J. Credle; Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine
  • Jonathan Gunn; Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine
  • Puwanat Sangkhapreecha; Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine
  • Daniel R. Monaco; Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine
  • Xuwen Alice Zheng; Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine
  • Hung-Ji Tsai; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston
  • Azaan Wilbon; Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine
  • William R. Morgenlander; Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine
  • Yi Dong; Center for Cell Dynamics and Department of Cell Biology, Johns Hopkins University School of Medicine
  • Sahana Jayaraman; Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine
  • Lorenzo Tosi; Department of Biomedical Engineering, Rutgers University
  • Biju Parekkadan; Department of Biomedical Engineering, Rutgers University
  • Alan N. Baer; Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine
  • Mario Roederer; ImmunoTechnology Section, Vaccine Research Center, NIAID, NIH
  • Evan M. Bloch; Division of Transfusion Medicine, Department of Pathology, Johns Hopkins University School of Medicine
  • Aaron A. R. Tobian; Division of Transfusion Medicine, Department of Pathology, Johns Hopkins University School of Medicine
  • Israel Zyskind; Department of Pediatrics, NYU Langone Medical Center, New York, NY and Maimonides Medical Center
  • Jonathan I. Silverberg; Department of Dermatology, George Washington University School of Medicine and Health Sciences
  • Avi Z. Rosenberg; Division of Transfusion Medicine, Department of Pathology, Johns Hopkins University
  • Andrea L. Cox; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University
  • Tom Lloyd; Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine
  • Andrew L. Mammen; Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH and Departments of Neurology and Medicine, Johns Hopkins Univers
  • H. Benjamin Larman; Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine
Preprint in English | bioRxiv | ID: ppbiorxiv-432977
ABSTRACT
Unbiased antibody profiling can identify the targets of an immune reaction. A number of likely pathogenic autoreactive antibodies have been associated with life-threatening SARS-CoV-2 infection; yet, many additional autoantibodies likely remain unknown. Here we present Molecular Indexing of Proteins by Self Assembly (MIPSA), a technique that produces ORFeome-scale libraries of proteins covalently coupled to uniquely identifying DNA barcodes for analysis by sequencing. We used MIPSA to profile circulating autoantibodies from 55 patients with severe COVID-19 against 11,076 DNA-barcoded proteins of the human ORFeome library. MIPSA identified previously known autoreactivities, and also detected undescribed neutralizing interferon lambda 3 (IFN-{lambda}3) autoantibodies. At-risk individuals with anti-IFN-{lambda}3 antibodies may benefit from interferon supplementation therapies, such as those currently undergoing clinical evaluation. One-Sentence SummaryMolecular Indexing of Proteins by Self Assembly (MIPSA) identifies neutralizing IFNL3 autoantibodies in patients with severe COVID-19. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/432977v1_ufig1.gif" ALT="Figure 1"> View larger version (25K) org.highwire.dtl.DTLVardef@a3c55aorg.highwire.dtl.DTLVardef@1f1c840org.highwire.dtl.DTLVardef@920bc7org.highwire.dtl.DTLVardef@43633e_HPS_FORMAT_FIGEXP M_FIG C_FIG
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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Experimental_studies / Prognostic study Language: English Year: 2021 Document type: Preprint
Fulltext
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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Experimental_studies / Prognostic study Language: English Year: 2021 Document type: Preprint