Citrullination of a phage-displayed human peptidome library reveals the fine specificities of rheumatoid arthritis-associated autoantibodies

Gabriel D. Román-Meléndez, Daniel R. Monaco, Janelle M. Montagne, Rachel S. Quizon, Maximilian F. Konig, Mekbib Astatke, Erika Darrah, Harry Larman

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Post-translational modifications (PTMs) on proteins can be targeted by antibodies associated with autoimmunity. Despite a growing appreciation for their intrinsic role in disease, there is a lack of highly multiplexed serological assays to characterize the fine specificities of PTM-directed autoantibodies. Methods: In this study, we used the programmable phage display technology, Phage ImmunoPrecipitation Sequencing (PhIP-Seq), to profile rheumatoid arthritis (RA) associated anti-citrullinated protein antibody (ACPA) reactivities. Findings: Using both unmodified and peptidylarginine deiminase (PAD)-modified phage display libraries consisting of ~250,000 overlapping 90 amino acid peptide tiles spanning the human proteome, PTM PhIP-Seq robustly identified antibodies to citrulline-dependent epitopes. Interpretation: PTM PhIP-Seq was used to quantify key differences among RA patients, including PAD isoform specific ACPA profiles, and thus represents a powerful tool for proteome-scale antibody-binding analyses.

Original languageEnglish (US)
Article number103506
JournalEBioMedicine
Volume71
DOIs
StatePublished - Sep 2021

Keywords

  • Citrullination
  • Peptidylarginine deiminase
  • Phage ImmunoPrecipitation Sequencing
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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