TY - JOUR
T1 - 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
AU - Schwenzer, Anja
AU - Quirke, Anne Marie
AU - Marzeda, Anna M.
AU - Wong, Alicia
AU - Montgomery, Anna B.
AU - Sayles, Harlan R.
AU - Eick, Sigrun
AU - Gawron, Katarzyna
AU - Chomyszyn-Gajewska, Maria
AU - Łazarz-Bartyzel, Katarzyna
AU - Davis, Simon
AU - Potempa, Jan
AU - Kessler, Benedikt M.
AU - Fischer, Roman
AU - Venables, Patrick J.
AU - Payne, Jeffrey B.
AU - Mikuls, Ted R.
AU - Midwood, Kim S.
PY - 2017/12
Y1 - 2017/12
N2 - Objective: 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. Methods: 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. Results: A novel citrullinated peptide cCK13-1 (444TSNASGR-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. Conclusion: 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.
AB - Objective: 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. Methods: 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. Results: A novel citrullinated peptide cCK13-1 (444TSNASGR-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. Conclusion: 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.
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U2 - 10.1002/art.40227
DO - 10.1002/art.40227
M3 - Article
C2 - 29084415
AN - SCOPUS:85033213709
VL - 69
SP - 2303
EP - 2313
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
SN - 2326-5191
IS - 12
ER -