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

Anja Schwenzer, Anne Marie Quirke, Anna M. Marzeda, Alicia Wong, Anna B. Montgomery, Harlan R. Sayles, Sigrun Eick, Katarzyna Gawron, Maria Chomyszyn-Gajewska, Katarzyna Łazarz-Bartyzel, Simon Davis, Jan Potempa, Benedikt M. Kessler, Roman Fischer, Patrick J. Venables, Jeffrey B Payne, Ted R Mikuls, Kim S. Midwood

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2303-2313
Number of pages11
JournalArthritis and Rheumatology
Volume69
Issue number12
DOIs
StatePublished - Dec 2017

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Prevotella intermedia
Periodontitis
Rheumatoid Arthritis
Gingival Crevicular Fluid
Peptides
Antibodies
Smoking
Vimentin
Fibrinogen
Antibody Formation
Epitopes
Keratin-13
Tenascin
Phosphopyruvate Hydratase
Osteoarthritis
Mass Spectrometry
Enzyme-Linked Immunosorbent Assay
Infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

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. / Schwenzer, Anja; Quirke, Anne Marie; Marzeda, Anna M.; Wong, Alicia; Montgomery, Anna B.; Sayles, Harlan R.; Eick, Sigrun; Gawron, Katarzyna; Chomyszyn-Gajewska, Maria; Łazarz-Bartyzel, Katarzyna; Davis, Simon; Potempa, Jan; Kessler, Benedikt M.; Fischer, Roman; Venables, Patrick J.; Payne, Jeffrey B; Mikuls, Ted R; Midwood, Kim S.

In: Arthritis and Rheumatology, Vol. 69, No. 12, 12.2017, p. 2303-2313.

Research output: Contribution to journalArticle

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 2017, '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', Arthritis and Rheumatology, vol. 69, no. 12, pp. 2303-2313. https://doi.org/10.1002/art.40227
Schwenzer, Anja ; Quirke, Anne Marie ; Marzeda, Anna M. ; Wong, Alicia ; Montgomery, Anna B. ; Sayles, Harlan R. ; Eick, Sigrun ; Gawron, Katarzyna ; Chomyszyn-Gajewska, Maria ; Łazarz-Bartyzel, Katarzyna ; Davis, Simon ; Potempa, Jan ; Kessler, Benedikt M. ; Fischer, Roman ; Venables, Patrick J. ; Payne, Jeffrey B ; Mikuls, Ted R ; Midwood, Kim S. / 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: Arthritis and Rheumatology. 2017 ; Vol. 69, No. 12. pp. 2303-2313.
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abstract = "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.",
author = "Anja Schwenzer and Quirke, {Anne Marie} and Marzeda, {Anna M.} and Alicia Wong and Montgomery, {Anna B.} and Sayles, {Harlan R.} and Sigrun Eick and Katarzyna Gawron and Maria Chomyszyn-Gajewska and Katarzyna Łazarz-Bartyzel and Simon Davis and Jan Potempa and Kessler, {Benedikt M.} and Roman Fischer and Venables, {Patrick J.} and Payne, {Jeffrey B} and Mikuls, {Ted R} and Midwood, {Kim S.}",
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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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