Brief Report: Anti-Carbamylated Protein Antibodies in Rheumatoid Arthritis Patients Are Reactive With Specific Epitopes of the Human Fibrinogen β-Chain
| Autor: | B. JoNell Hamilton, William F.C. Rigby, Jonathan D. Jones |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
030203 arthritis & rheumatology
0301 basic medicine Homocitrulline biology Immunology Arthritis medicine.disease Fibrinogen Molecular biology Epitope Human fibrinogen 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Rheumatology chemistry Rheumatoid arthritis medicine biology.protein Immunology and Allergy Antibody Polyacrylamide gel electrophoresis medicine.drug |
| Zdroj: | Arthritis & Rheumatology. 69:1381-1386 |
| ISSN: | 2326-5191 |
| DOI: | 10.1002/art.40098 |
| Popis: | Objective: Anti-carbamylated protein antibodies (ACarPA) are associated with rheumatoid arthritis (RA) risk and severity and are primarily directed against fibrinogen. The lack of understanding of ACarPA reactivity has limited analysis of their immunopathogenic associations in RA. To address this shortcoming, we mapped ACarPA epitope reactivity in RA patient sera. Methods: Immunoblotting identified a patient serum with specific reactivity to carbamylated human fibrinogen β-chain. Liquid chromatography/mass spectrometry (LC/MS) identified sites of homocitrullines (carbamylated lysines) present in the human fibrinogen β-chain. The reactivity of an ACarPA+ cohort to specific peptides containing carbamylated lysines was determined by ELISA through direct binding (n=63) and by competition assays (n=40). Results: Serum from an RA patient with specific reactivity to carbamylated, but not citrullinated, fibrinogen β-chain was identified. LC/MS identified carbamylation of 9/34 lysines in the human fibrinogen β-chain. Mapping of immunoreactivity against tryptic peptide fragments demonstrated several candidate carbamylated epitopes that were confirmed by competition experiments. Peptides containing a homocitrulline at position 83 appeared to be an immunodominant epitope in some RA patient sera, with additional reactivity to peptides containing homocitrullines at positions 52, 264, 351, 367, and 374. Conclusion: ACarPA appear to preferentially target specific regions of the human fibrinogen β-chain that contain homocitrullines. Interestingly, humoral immunoreactivity appears relatively restricted in some patients, which may enable detection of specific relationships with disease phenotype. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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