Abstract
BackgroundAntibodies to citrullinated proteins (ACPA) occur years before RA diagnosis. Porphyromonas gingivalis expresses its own peptidylarginine deiminase (PPAD), and is a proposed aetiological factor for the ACPA response. Smoking is a risk factor for both ACPA-positive RA and periodontitis. We aimed to study the relation of these factors to the risk of RA in a prospective cohort.MethodsWe performed a nested case–control study by identifying pre-RA cases in four populations from the European Prospective Investigation into Cancer and nutrition, matched with three controls. Data on smoking and other covariates were obtained from baseline questionnaires. Antibodies to CCP2 and citrullinated peptides from α-enolase, fibrinogen, vimentin and PPAD were measured. Antibodies to arginine gingipain (RgpB) were used as a marker for P.gingivalis infection and validated in a separate cohort of healthy controls and subjects with periodontitis.ResultsWe studied 103 pre-RA cases. RA development was associated with several ACPA specificities, but not with antibodies to citrullinated PPAD peptides. Antibody levels to RgpB and PPAD peptides were higher in smokers but were not associated with risk of RA or with pre-RA autoimmunity. Former but not current smoking was associated with antibodies to α-enolase (OR 4.06; 95 % CI 1.02, 16.2 versus 0.54; 0.09-3.73) and fibrinogen peptides (OR 4.24; 95 % CI 1.2-14.96 versus 0.58; 0.13-2.70), and later development of RA (OR 2.48; 95 % CI 1.27-4.84 versus 1.57; 0.85-2.93), independent of smoking intensity.ConclusionsSmoking remains a risk factor for RA well before the clinical onset of disease. In this cohort, P.gingivalis is not associated with pre-RA autoimmunity or risk of RA in an early phase before disease-onset. Antibodies to PPAD peptides are not an early feature of ACPA ontogeny.
Highlights
Antibodies to citrullinated proteins (ACPA) occur years before Rheumatoid arthritis (RA) diagnosis
Recent data suggest that the epitopes that break tolerance may differ between individuals, and from those most strongly associated with the clinical onset of disease, indicating that epitope spreading may be intimately related to disease onset [5]
We have shown that citrullinated peptides from peptidylarginine deiminase (PPAD) are a target of the anti-citrullinated protein/ peptide antibodies (ACPA) response in a subset of patients with RA [10], though it remains unclear whether this response is driven by citrullination of PPAD [14] or whether it is part of a polyreactive ACPA response
Summary
Antibodies to citrullinated proteins (ACPA) occur years before RA diagnosis. We aimed to study the relation of these factors to the risk of RA in a prospective cohort. An autoimmune pathogenesis is supported by the strong association with anti-citrullinated protein/ peptide antibodies (ACPA), which occur in 50-80 % of cases and may be detected many years before the onset of clinical symptoms. Risk factors for one phase may not be so for others. ACPA responses are characterised by differing but overlapping patterns of reactivity to several citrullinated autoantigens, and the number of such specificities increase prior to the clinical onset of joint disease [2,3,4]. Recent data suggest that the epitopes that break tolerance may differ between individuals, and from those most strongly associated with the clinical onset of disease, indicating that epitope spreading may be intimately related to disease onset [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
