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Correspondence response
Response to: ‘The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis? Antibodies against uncitrullinated peptides seem to occur prior to the antibodies to the corresponding citrullinated peptides’ by Brink et al We would like to thank Brink et al1 for their interest in our paper. The authors reported that antibodies against arginine-containing peptides from rheumatoid arthritis (RA) autoantigens were present in a population-based sample of 386 individuals with pre-RA. These pre-dated the corresponding antibodies against citrullinated peptides which appeared closer to onset of symptoms. These results are in line with our results, if it is proposed that periodontitis is a disease which may break tolerance to citrullinated antigens. In patients with periodontitis2 we observed a significantly raised frequency of antibodies against uncitrullinated (arginine) peptides for α-enolase peptide-1, and fibrinogen, as well as citrullinated α-enolase peptide-1 compared to controls without periodontal disease. Interestingly, a recent study by Lappin et al3 confirmed our results by showing that the autoantibody response in periodontitis is predominantly directed to the uncitrullinated peptide from α-enolase. Taken together, these results suggest that there are two stages of the development of ACPA: the first stage in which antibodies against arginine peptides appear, followed by a second stage in which antibodies against citrullinated peptides develop. This is supported by Brink’s work1 though we can only speculate that periodontitis has contributed to the increased autoantibody seropositivity in their pre-RA patients, as data on periodontitis were not available. However, periodontitis is a very common disease: among 40-year-olds in Sweden the prevalence was >30% in 2003.4 We concur with Brink et al1 that further studies in large samples on the emergence of autoantibodies in periodontitis and pre-RA are warranted. Paola de Pablo,1 Thomas Dietrich,2 Iain L C Chapple,3 Michael Milward,3 Christopher D Buckley,1 Patrick J Venables4 1
Rheumatology Research Group, School of Immunity & Infection, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK
Ann Rheum Dis July 2014 Vol 73 No 7
2
Department of Oral Surgery, School of Dentistry, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK 3 Department of Periodontology, School of Dentistry, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK 4 Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK Correspondence to Dr Paola de Pablo, Rheumatology Research Group, School of Immunity & Infection, College of Medical & Dental Sciences, University of Birmingham, Birmingham B15 2WB, UK; [email protected] Contributors All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version. Funding This work was supported by ‘Gums & Joints’, a European Union FP7 Grant FP7 HEALTH-F2-2010-261460 and ‘RAPID’, a European Union funded ITN project 290246. Competing interests None. Provenance and peer review Commissioned; internally peer reviewed.
To cite de Pablo P, Dietrich T, Chapple ILC, et al. Ann Rheum Dis 2014;73:e47. Received 26 March 2014 Accepted 29 March 2014 Published Online First 19 April 2014
▸ http://dx.doi.org/10.1136/annrheumdis-2014-205498 Ann Rheum Dis 2014;73:e47. doi:10.1136/annrheumdis-2014-205519
REFERENCES 1
2
3
4
Brink M, Hansson M, Ronnelid J, et al. Letter to the Editor. Response to ‘The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis?’ by de Pablo et al. Ann Rheum Dis 2014;73:e46. de Pablo P, Dietrich T, Chapple IL, et al. The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis? Ann Rheum Dis 2014;73:580–6. Lappin DF, Apatzidou D, Quirke AM, et al. Influence of periodontal disease, Porphyromonas gingivalis and cigarette smoking on systemic anti-citrullinated peptide antibody titres. J Clin Periodontol 2013;40:907–15. Hugoson A, Sjodin B, Norderyd O. Trends over 30 years, 1973–2003, in the prevalence and severity of periodontal disease. J Clin Periodontol 2008;35: 405–14.
e47
Downloaded from ard.bmj.com on September 27, 2014 - Published by group.bmj.com
Response to: 'The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis? Antibodies against uncitrullinated peptides seem to occur prior to the antibodies to the corresponding citrullinated peptides' by Brink et al Paola de Pablo, Thomas Dietrich, Iain L C Chapple, et al. Ann Rheum Dis 2014 73: e47 originally published online April 19, 2014
doi: 10.1136/annrheumdis-2014-205519
Updated information and services can be found at: http://ard.bmj.com/content/73/7/e47.full.html
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References
This article cites 3 articles, 1 of which can be accessed free at: http://ard.bmj.com/content/73/7/e47.full.html#ref-list-1
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Correspondence response
Response to: ‘The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis? Antibodies against uncitrullinated peptides seem to occur prior to the antibodies to the corresponding citrullinated peptides’ by Brink et al We would like to thank Brink et al1 for their interest in our paper. The authors reported that antibodies against arginine-containing peptides from rheumatoid arthritis (RA) autoantigens were present in a population-based sample of 386 individuals with pre-RA. These pre-dated the corresponding antibodies against citrullinated peptides which appeared closer to onset of symptoms. These results are in line with our results, if it is proposed that periodontitis is a disease which may break tolerance to citrullinated antigens. In patients with periodontitis2 we observed a significantly raised frequency of antibodies against uncitrullinated (arginine) peptides for α-enolase peptide-1, and fibrinogen, as well as citrullinated α-enolase peptide-1 compared to controls without periodontal disease. Interestingly, a recent study by Lappin et al3 confirmed our results by showing that the autoantibody response in periodontitis is predominantly directed to the uncitrullinated peptide from α-enolase. Taken together, these results suggest that there are two stages of the development of ACPA: the first stage in which antibodies against arginine peptides appear, followed by a second stage in which antibodies against citrullinated peptides develop. This is supported by Brink’s work1 though we can only speculate that periodontitis has contributed to the increased autoantibody seropositivity in their pre-RA patients, as data on periodontitis were not available. However, periodontitis is a very common disease: among 40-year-olds in Sweden the prevalence was >30% in 2003.4 We concur with Brink et al1 that further studies in large samples on the emergence of autoantibodies in periodontitis and pre-RA are warranted. Paola de Pablo,1 Thomas Dietrich,2 Iain L C Chapple,3 Michael Milward,3 Christopher D Buckley,1 Patrick J Venables4 1
Rheumatology Research Group, School of Immunity & Infection, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK
Ann Rheum Dis July 2014 Vol 73 No 7
2
Department of Oral Surgery, School of Dentistry, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK 3 Department of Periodontology, School of Dentistry, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK 4 Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK Correspondence to Dr Paola de Pablo, Rheumatology Research Group, School of Immunity & Infection, College of Medical & Dental Sciences, University of Birmingham, Birmingham B15 2WB, UK; [email protected] Contributors All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version. Funding This work was supported by ‘Gums & Joints’, a European Union FP7 Grant FP7 HEALTH-F2-2010-261460 and ‘RAPID’, a European Union funded ITN project 290246. Competing interests None. Provenance and peer review Commissioned; internally peer reviewed.
To cite de Pablo P, Dietrich T, Chapple ILC, et al. Ann Rheum Dis 2014;73:e47. Received 26 March 2014 Accepted 29 March 2014 Published Online First 19 April 2014
▸ http://dx.doi.org/10.1136/annrheumdis-2014-205498 Ann Rheum Dis 2014;73:e47. doi:10.1136/annrheumdis-2014-205519
REFERENCES 1
2
3
4
Brink M, Hansson M, Ronnelid J, et al. Letter to the Editor. Response to ‘The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis?’ by de Pablo et al. Ann Rheum Dis 2014;73:e46. de Pablo P, Dietrich T, Chapple IL, et al. The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis? Ann Rheum Dis 2014;73:580–6. Lappin DF, Apatzidou D, Quirke AM, et al. Influence of periodontal disease, Porphyromonas gingivalis and cigarette smoking on systemic anti-citrullinated peptide antibody titres. J Clin Periodontol 2013;40:907–15. Hugoson A, Sjodin B, Norderyd O. Trends over 30 years, 1973–2003, in the prevalence and severity of periodontal disease. J Clin Periodontol 2008;35: 405–14.
e47
Downloaded from ard.bmj.com on September 27, 2014 - Published by group.bmj.com
Response to: 'The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis? Antibodies against uncitrullinated peptides seem to occur prior to the antibodies to the corresponding citrullinated peptides' by Brink et al Paola de Pablo, Thomas Dietrich, Iain L C Chapple, et al. Ann Rheum Dis 2014 73: e47 originally published online April 19, 2014
doi: 10.1136/annrheumdis-2014-205519
Updated information and services can be found at: http://ard.bmj.com/content/73/7/e47.full.html
These include:
References
This article cites 3 articles, 1 of which can be accessed free at: http://ard.bmj.com/content/73/7/e47.full.html#ref-list-1
Email alerting service
Topic Collections
Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Articles on similar topics can be found in the following collections Immunology (including allergy) (4340 articles) Connective tissue disease (3650 articles) Degenerative joint disease (3977 articles) Musculoskeletal syndromes (4252 articles) Rheumatoid arthritis (2785 articles)
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions
To order reprints go to: http://journals.bmj.com/cgi/reprintform
To subscribe to BMJ go to: http://group.bmj.com/subscribe/
