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

15 Scopus citations

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

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Schwenzer, A., Quirke, A. M., Marzeda, A. M., Wong, A., Montgomery, A. B., Sayles, H. R., Eick, S., Gawron, K., Chomyszyn-Gajewska, M., Łazarz-Bartyzel, K., Davis, S., Potempa, J., Kessler, B. M., Fischer, R., Venables, P. J., Payne, J. B., Mikuls, T. R., & Midwood, K. S. (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, 69(12), 2303-2313. https://doi.org/10.1002/art.40227