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COVID-19

Unbiased Discovery of Autoantibodies Associated with Severe COVID-19 via Genome-Scale Self-Assembled DNA-Barcoded Protein Libraries

Strategic Insights

— 2 min read

Researchers at Johns Hopkins University have developed a novel approach to identify pathogenic autoreactive antibodies associated with severe COVID-19. By using genome-scale libraries of full-length proteins covalently coupled to unique DNA barcodes, the team was able to detect circulating neutralizing type-I and type-III interferon (IFN) autoantibodies in patient plasma. The method, named MIPSA (Molecular Indexing of Proteins by Self-Assembly), offers a low-cost and simple workflow for unbiased high-throughput analyses of protein-antibody, protein-protein, and protein-small-molecule interactions.

Key Takeaways:

  • The research utilized a genome-scale library of 11,076 DNA-barcoded proteins to identify autoreactive antibodies in plasma samples from patients with life-threatening COVID-19.
  • The MIPSA method allowed the detection of circulating neutralizing type-I and type-III IFN autoantibodies, as well as previously known autoreactive antibodies in patient plasma.
  • The method also identified as yet unidentified neutralizing type-III anti-IFN-lambda 3 autoantibodies not seen in healthy plasma samples or in convalescent plasma from 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.
  • The research was supported by the Johns Hopkins University Provost Research Grant, NIH National Institute of General Medical Sciences, NIH National Heart Lung & Blood Institute, Sjogren's Syndrome Foundation, Jerome L. Greene Foundation, NIH National Institute of Allergy & Infectious Diseases, and NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases.
  • The study's lead author, H. Benjamin Larman, states that the MIPSA method has the potential to facilitate the unbiased identification of autoreactive antibodies associated with severe COVID-19.

Statistics:

  • 11,076 DNA-barcoded proteins were used to create the genome-scale library.
  • 55 patients with life-threatening COVID-19 were studied, and 5 plasma samples showed detectable circulating neutralizing type-I and type-III IFN autoantibodies.
  • The research took place at Johns Hopkins University, Department of Pathology, Division of Immunology, Institute for Cell Engineering, Baltimore, MD 21205, United States.
  • The study's authors include Joel J. Credle, Jonathan Gunn, Puwanat Sangkhapreecha, Daniel R. Monaco, Xuwen Alice Zheng, Azaan Wilbon, William R. Morgenlander, Andre Rastegar, Sahana Jayaraman, Hung-Ji Tsai, Yi Dong, Lorenzo Tosi, Biju Parekkadan, Alan N. Baer, Mario Roederer, Evan M. Bloch, Aaron A. R. Tobian, Israel Zyskind, Jonathan Silverberg, Avi Z. Rosenberg, Andrea L. Cox, Tom Lloyd, and Andrew L. Mammen.

Sources:

  • Unbiased Discovery of Autoantibodies Associated With Severe Covid-19 Via Genome-scale Self-assembled Dna-barcoded Protein Libraries. Nature Biomedical Engineering, 2022;6(8).
  • Nature Biomedical Engineering, Nature Portfolio, Heidelberger Platz 3, Berlin, 14197, Germany.
  • Findings from Johns Hopkins University Yields New Findings on Protein Libraries (Unbiased Discovery of Autoantibodies Associated With Severe Covid-19 Via Genome-scale Self-assembled Dna-barcoded Protein Libraries). Proteomics Weekly. September 19, 2022; p 197.

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