Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case–control study

Fisher, B. A. et al. (2015) Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case–control study. BMC Musculoskeletal Disorders, 16, 331. (doi:10.1186/s12891-015-0792-y) (PMID:26537917) (PMCID:PMC4634856)

[img]
Preview
Text
130037.pdf - Published Version
Available under License Creative Commons Attribution.

718kB

Abstract

Background: Antibodies 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. Methods: We 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. Results: We 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. Conclusions: Smoking 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.

Item Type:Articles
Additional Information:A correction is available to this article at http://dx.doi.org/10.1186/s12891-016-0916-z.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lappin, Dr David and Culshaw, Professor Shauna
Authors: Fisher, B. A., Cartwright, A. J., Quirke, A.-M., de Pablo, P., Romaguera, D., Panico, S., Mattiello, A., Gavrila, D., Navarro, C., Sacerdote, C., Vineis, P., Tumino, R., Lappin, D. F., Apazidou, D., Culshaw, S., Potempa, J., Michaud, D. S., Riboli, E., and Venables, P. J.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:BMC Musculoskeletal Disorders
Publisher:BioMed Central
ISSN:1471-2474
ISSN (Online):1471-2474
Copyright Holders:Copyright © 2015 Fisher et al.
First Published:First published in BMC Musculoskeletal Disorders 16:331
Publisher Policy:Reproduced under a Creative Commons License
Related URLs:

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
554151BTCureJames BrewerEuropean Commission (EC)115142III -IMMUNOLOGY
535611Gums and JointsShauna CulshawEuropean Commission (EC)261460SM - DENTAL SCHOOL