Association of distinct fine specificities of anti-citrullinated peptide antibodies with elevated immune responses to prevotella intermedia in a subgroup of patients with rheumatoid arthritis and periodontitis
In addition to the long-established link with smoking, periodontitis (PD) is a risk factor for rheumatoid arthritis (RA). This study was undertaken to elucidate the mechanism by which PD could induce antibodies to citrullinated peptides (ACPAs), by examining the antibody response to a novel citrulli...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2017
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| _version_ | 1797067189325398016 |
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| author | Schwenzer, A Quirke, AM Marzeda, AM Wong, A Montgomery, AB Sayles, HR Eick, S Gawron, K Chomyszyn-Gajewska, M Łazarz-Bartyzel, K Davis, S Potempa, J Kessler, BM Fischer, R Venables, PJ Payne, JB Mikuls, TR Midwood, KS |
| author_facet | Schwenzer, A Quirke, AM Marzeda, AM Wong, A Montgomery, AB Sayles, HR Eick, S Gawron, K Chomyszyn-Gajewska, M Łazarz-Bartyzel, K Davis, S Potempa, J Kessler, BM Fischer, R Venables, PJ Payne, JB Mikuls, TR Midwood, KS |
| author_sort | Schwenzer, A |
| collection | OXFORD |
| description | In addition to the long-established link with smoking, periodontitis (PD) is a risk factor for rheumatoid arthritis (RA). This study was undertaken to elucidate the mechanism by which PD could induce antibodies to citrullinated peptides (ACPAs), by examining the antibody response to a novel citrullinated peptide of cytokeratin 13 (CK-13) identified in gingival crevicular fluid (GCF), and comparing the response to 4 other citrullinated peptides in patients with RA who were well-characterized for PD and smoking.The citrullinomes of GCF and periodontal tissue from patients with PD were mapped by mass spectrometry. ACPAs of CK13 (cCK13), tenascin-C (cTNC5), vimentin (cVIM), α-enolase (CEP-1), and fibrinogen β (cFIBβ) were examined by enzyme-linked immunosorbent assay in patients with RA (n = 287) and patients with osteoarthritis (n = 330), and cross-reactivity was assessed by inhibition assays.A novel citrullinated peptide cCK13-1 (444 TSNASGR-Cit-TSDV-Cit-RP458 ) identified in GCF exhibited elevated antibody responses in RA patients (24%). Anti-cCK13-1 antibody levels correlated with anti-cTNC5 antibody levels, and absorption experiments confirmed this was not due to cross-reactivity. Only anti-cCK13-1 and anti-cTNC5 were associated with antibodies to the periodontal pathogen Prevotella intermedia (P = 0.05 and P = 0.001, respectively), but not with antibodies to Porphyromonas gingivalis arginine gingipains. Levels of antibodies to CEP-1, cFIBβ, and cVIM correlated with each other, and with smoking and shared epitope risk factors in RA.This study identifies 2 groups of ACPA fine specificities associated with different RA risk factors. One is predominantly linked to smoking and shared epitope, and the other links anti-cTNC5 and cCK13-1 to infection with the periodontal pathogen P intermedia. |
| first_indexed | 2024-03-06T21:52:48Z |
| format | Journal article |
| id | oxford-uuid:4be0f516-7bcc-41e9-a481-4c5bb01a0913 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:52:48Z |
| publishDate | 2017 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:4be0f516-7bcc-41e9-a481-4c5bb01a09132022-03-26T15:46:15ZAssociation of distinct fine specificities of anti-citrullinated peptide antibodies with elevated immune responses to prevotella intermedia in a subgroup of patients with rheumatoid arthritis and periodontitisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4be0f516-7bcc-41e9-a481-4c5bb01a0913EnglishSymplectic Elements at OxfordWiley2017Schwenzer, AQuirke, AMMarzeda, AMWong, AMontgomery, ABSayles, HREick, SGawron, KChomyszyn-Gajewska, MŁazarz-Bartyzel, KDavis, SPotempa, JKessler, BMFischer, RVenables, PJPayne, JBMikuls, TRMidwood, KSIn addition to the long-established link with smoking, periodontitis (PD) is a risk factor for rheumatoid arthritis (RA). This study was undertaken to elucidate the mechanism by which PD could induce antibodies to citrullinated peptides (ACPAs), by examining the antibody response to a novel citrullinated peptide of cytokeratin 13 (CK-13) identified in gingival crevicular fluid (GCF), and comparing the response to 4 other citrullinated peptides in patients with RA who were well-characterized for PD and smoking.The citrullinomes of GCF and periodontal tissue from patients with PD were mapped by mass spectrometry. ACPAs of CK13 (cCK13), tenascin-C (cTNC5), vimentin (cVIM), α-enolase (CEP-1), and fibrinogen β (cFIBβ) were examined by enzyme-linked immunosorbent assay in patients with RA (n = 287) and patients with osteoarthritis (n = 330), and cross-reactivity was assessed by inhibition assays.A novel citrullinated peptide cCK13-1 (444 TSNASGR-Cit-TSDV-Cit-RP458 ) identified in GCF exhibited elevated antibody responses in RA patients (24%). Anti-cCK13-1 antibody levels correlated with anti-cTNC5 antibody levels, and absorption experiments confirmed this was not due to cross-reactivity. Only anti-cCK13-1 and anti-cTNC5 were associated with antibodies to the periodontal pathogen Prevotella intermedia (P = 0.05 and P = 0.001, respectively), but not with antibodies to Porphyromonas gingivalis arginine gingipains. Levels of antibodies to CEP-1, cFIBβ, and cVIM correlated with each other, and with smoking and shared epitope risk factors in RA.This study identifies 2 groups of ACPA fine specificities associated with different RA risk factors. One is predominantly linked to smoking and shared epitope, and the other links anti-cTNC5 and cCK13-1 to infection with the periodontal pathogen P intermedia. |
| spellingShingle | Schwenzer, A Quirke, AM Marzeda, AM Wong, A Montgomery, AB Sayles, HR Eick, S Gawron, K Chomyszyn-Gajewska, M Łazarz-Bartyzel, K Davis, S Potempa, J Kessler, BM Fischer, R Venables, PJ Payne, JB Mikuls, TR Midwood, KS Association of distinct fine specificities of anti-citrullinated peptide antibodies with elevated immune responses to prevotella intermedia in a subgroup of patients with rheumatoid arthritis and periodontitis |
| title | Association of distinct fine specificities of anti-citrullinated peptide antibodies with elevated immune responses to prevotella intermedia in a subgroup of patients with rheumatoid arthritis and periodontitis |
| title_full | Association of distinct fine specificities of anti-citrullinated peptide antibodies with elevated immune responses to prevotella intermedia in a subgroup of patients with rheumatoid arthritis and periodontitis |
| title_fullStr | Association of distinct fine specificities of anti-citrullinated peptide antibodies with elevated immune responses to prevotella intermedia in a subgroup of patients with rheumatoid arthritis and periodontitis |
| title_full_unstemmed | Association of distinct fine specificities of anti-citrullinated peptide antibodies with elevated immune responses to prevotella intermedia in a subgroup of patients with rheumatoid arthritis and periodontitis |
| title_short | Association of distinct fine specificities of anti-citrullinated peptide antibodies with elevated immune responses to prevotella intermedia in a subgroup of patients with rheumatoid arthritis and periodontitis |
| title_sort | association of distinct fine specificities of anti citrullinated peptide antibodies with elevated immune responses to prevotella intermedia in a subgroup of patients with rheumatoid arthritis and periodontitis |
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