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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
Author(s) -
Schwenzer Anja,
Quirke AnneMarie,
Marzeda Anna M.,
Wong Alicia,
Montgomery Anna B.,
Sayles Harlan R.,
Eick Sigrun,
Gawron Katarzyna,
ChomyszynGajewska Maria,
ŁazarzBartyzel Katarzyna,
Davis Simon,
Potempa Jan,
Kessler Benedikt M.,
Fischer Roman,
Venables Patrick J.,
Payne Jeffrey B.,
Mikuls Ted R.,
Midwood Kim S.
Publication year - 2017
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40227
Subject(s) - porphyromonas gingivalis , prevotella intermedia , periodontitis , antibody , citrullination , medicine , immunology , rheumatoid arthritis , arthritis , rheumatoid factor , autoantibody , citrulline , chemistry , arginine , biochemistry , amino acid
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 ( ACPA s), 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. ACPA s of CK 13 ( cCK 13), tenascin‐C ( cTNC 5), vimentin ( cVIM ), α‐enolase ( CEP ‐1), and fibrinogen β ( cFIB β) 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 cCK 13‐1 ( 444 TSNASGR ‐Cit‐ TSDV ‐Cit‐ RP 458 ) identified in GCF exhibited elevated antibody responses in RA patients (24%). Anti– cCK 13‐1 antibody levels correlated with anti– cTNC 5 antibody levels, and absorption experiments confirmed this was not due to cross‐reactivity. Only anti– cCK 13‐1 and anti‐ cTNC 5 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, cFIB β, 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– cTNC 5 and cCK 13‐1 to infection with the periodontal pathogen P intermedia .