Neutralizing IFNL3 Autoantibodies in Severe COVID-19 Identified Using Molecular Indexing of Proteins by Self-Assembly.

BioRxiv : the Preprint Server for Biology
Joel J CredleH Benjamin Larman

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-λ3) autoantibodies. At-risk individuals with anti-IFN-λ3 antibodies may benefit from interferon supplementation therapies, such as those currently undergoing clinical evaluation. Molecular Indexing of Proteins by Self Assembly (MIPSA) identifies neutralizing IFNL3 autoantibodies in patients with severe COVID-19.

Methods Mentioned

BETA
phage display
ELISA
protein array
PCR
Destination
Illumina sequencing
PhIP-Seq
antibody
protein display

Clinical Trials Mentioned

NCT04343976
NCT04534673
NCT04344600
NCT04354259

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