Citrullination of a phage-displayed human peptidome library reveals the fine specificities of rheumatoid arthritis-associated autoantibodies
Year: 2021
Type: article
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. FUNDING: This research is based upon work supported in part by the Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA). The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies, either expressed or implied, of ODNI, IARPA, or the US Government. The US Government is authorized to reproduce and distribute reprints for governmental purposes notwithstanding any copyright annotation therein. This study was made possible by a National Institute of General Medical Sciences (NIGMS) grant R01 GM136724 (HBL). MFK was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grant T32AR048522. ED was supported by the Rheumatology Research Foundation.
Source: EBioMedicine
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,500
Funders: American College of Rheumatology Research and Education Foundation, Rheumatology Research Foundation, Office of the Director of National Intelligence, Government of South Australia, Intelligence Advanced Research Projects Activity, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1254073724, G2181677361, G2352776544, G2365361987, G3190307233, G3190892274, Design and Analysis of Displayed Peptidomes, G351092240, G3563259462, G5033367359, Development of Highly Multiplex Antigen Specificity Assays, G571182435, G8643976304, Multidisciplinary Rheumatology Training Program
OpenAlex ID: W3197453979