Rheumatoid arthritis sera antibodies to citrullinated collagen type II bind to joint cartilage.
Anti-citrullinated type II collagen antibodies
Osteoarthritis
Rheumatoid arthritis
Journal
Arthritis research & therapy
ISSN: 1478-6362
Titre abrégé: Arthritis Res Ther
Pays: England
ID NLM: 101154438
Informations de publication
Date de publication:
22 11 2022
22 11 2022
Historique:
received:
28
08
2022
accepted:
03
11
2022
entrez:
24
11
2022
pubmed:
25
11
2022
medline:
26
11
2022
Statut:
epublish
Résumé
To investigate the occurrence and frequency of anti-citrullinated protein antibodies (ACPA) to cyclic citrullinated type II collagen (COL2) epitope with a capacity to bind joint cartilage. Luminex immunoassay was used to analyze serum antibody reactivity to 10 COL2-citrullinated peptides (ACC10) and corresponding arginine peptide controls in rheumatoid arthritis (RA), osteoarthritis (OA), and healthy individuals' cohorts. Top ten "promiscuous" sera (cross-reactive with all ACC10) and top ten "private" sera (restrictedly reactive with one ACC10 peptide) from RA and OA cohorts were selected. Enzyme-linked immunosorbent assay (ELISA) was used to detect response to native COL2. Sera were analyzed with naive and arthritic joints from DBA/1J mice by immunohistochemistry, using monoclonal ACPAs and COL2 reactive antibodies with human Fc as comparison. Staining specificity was confirmed with C1 (a major antibody epitope on COL2) mutated mice and competitive blocking with epitope-specific antibodies. All patient sera bound ACC10 compared with control peptides but very few (3/40) bound native triple-helical COL2. Most sera (27/40) specifically bound to arthritic cartilage, whereas only one private RA serum bound to healthy cartilage. Despite very low titers, private sera from both RA and OA showed an epitope-specific response, documented by lack of binding to cartilage from C1-mutated mice and blocking binding to wild-type cartilage with a competitive monoclonal antibody. As a comparison, monoclonal ACPAs visualized typical promiscuous, or private reactivity to joint cartilage and other tissues. ACPA from RA and OA sera, reactive with citrullinated non-triple-helical COL2 peptides, can bind specifically to arthritic cartilage.
Identifiants
pubmed: 36419093
doi: 10.1186/s13075-022-02945-0
pii: 10.1186/s13075-022-02945-0
pmc: PMC9682822
doi:
Substances chimiques
acetyl 4-aminosalicylic acid
102338-89-6
Autoantibodies
0
Collagen Type II
0
Epitopes
0
Myeloblastin
EC 3.4.21.76
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
257Informations de copyright
© 2022. The Author(s).
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