We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Citrulline Not a Major Determinant in the Recognition of Peptidylarginine Deiminase 2 and 4 by Autoantibodies in Rheumatoid Arthritis.
- Authors
Darrah, Erika; Davis, Ryan L.; Curran, Ashley M.; Naik, Pooja; Chen, Ruiqiang; Na, Chan Hyun; Giles, Jon T.; Andrade, Felipe
- Abstract
Objective: Citrullinated proteins are hallmark targets of autoantibodies in rheumatoid arthritis (RA). Our study was undertaken to determine the effect of autocitrullination on the recognition of peptidylarginine deiminases (PADs) 2 and 4 by autoantibodies in RA. Methods: Autocitrullination sites in PAD2 and PAD4 were determined by mass spectrometry and literature review. Antibodies against native and autocitrullinated PADs in 184 patients with RA were detected by enzyme‐linked immunosorbent assay. Linear regression analysis, outlier calculations, and competition assays were performed to evaluate antibody reactivity to native and citrullinated PADs. Results: Autocitrullination of PAD2 and PAD4 was detected in 16 (48%) of 33 arginine residues and 7 (26%) of 27 arginine residues, respectively. Despite robust autocitrullination, autoantibodies bound similarly to native and citrullinated PAD2 or PAD4 (ρ = 0.927 and ρ = 0.903, respectively; each P < 0.0001). Although subsets of anti‐PAD–positive sera were identified as exhibiting preferential recognition of native or citrullinated PAD2 (40.5% or 4.8%, respectively) or PAD4 (11.7% or 10.4%, respectively), competition assays confirmed that the majority of anti‐PAD reactivity was attributed to a pool of autoantibodies that bound irrespective of citrullination status. Conclusion: Autocitrullination does not affect autoantibody reactivity to PADs in the majority of patients with RA, demonstrating that anti‐PAD antibodies are distinct from anti–citrullinated protein antibodies in their dependence on citrullination for binding.
- Subjects
AMINO acids; ARGININE; AUTOANTIBODIES; ENZYME-linked immunosorbent assay; HYDROLASES; MASS spectrometry; REGRESSION analysis; RHEUMATOID arthritis; DESCRIPTIVE statistics
- Publication
Arthritis & Rheumatology, 2020, Vol 72, Issue 9, p1476
- ISSN
2326-5191
- Publication type
Article
- DOI
10.1002/art.41276