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

Patrick J. Venables⁸  Elio Riboli⁴  Dominique S. Michaud⁴  Jan Potempa¹  Shauna Culshaw²  Danae Apazidou²  David F. Lappin²  Rosario Tumino^1,10  Paolo Vineis⁹  Carlotta Sacerdote⁹  Carmen Navarro⁵  Diana Gavrila⁵  Amalia Mattiello⁶  Salvatore Panico⁶  Dora Romaguera³  Paola de Pablo⁷  Anne-Marie Quirke⁸  Alison J. Cartwright⁸  Benjamin A. Fisher⁷ 

[1] Oral Health and Systemic Research Group, School of Dentistry, University of Louisville, Louisville, USA;University of Glasgow Dental School, University of Glasgow, Glasgow, UK;CIBER-OBN (Fisiopatología de la Obesidad y Nutrición), Madrid, Spain;School of Public Health, Imperial College London, London, UK;CIBER Epidemiología y Salud Pública (CIBERESP), Murcia, Spain;Department of Clinical and Experimental Medicine, Federico II University of Naples, Naples, Italy;Rheumatology Research Group, Centre for Translational Inflammation Research, Queen Elizabeth Hospital Birmingham, Birmingham B15 2WB, UK;Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK;Human Genetics Foundation, Turin, Italy;Cancer Registry and Histopathology Unit, “Civic - M.P.Arezzo” Hospital, ASP Ragusa, Ragusa, Italy

关键词: Citrullination;    Porphyromonas gingivalis;    Anti-citrullinated protein antibodies (ACPA);    Rheumatoid arthritis (RA);    Smoking;   

Others  :  1234046
DOI  :  10.1186/s12891-015-0792-y

 received in 2015-09-05, accepted in 2015-10-24,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Fisher et al.

【 图 表 】

Fig. 1.

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