Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis.
Ted R. Mikuls,Jeffrey B. Payne,Fang Yu,Geoffrey M. Thiele,Richard J. Reynolds,Grant W. Cannon,Jeffrey Markt,David McGowan,Gail S. Kerr,Robert S. Redman,Andreas M. Reimold,Garth R. Griffiths,Mark W. Beatty,Shawneen M. Gonzalez,Debra A. Bergman,Bartlett C. Hamilton,Alan R Erickson,Jeremy Sokolove,William H. Robinson,Clay Walker,Fatiha Chandad,James R. O'Dell +21 more
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TLDR
To examine the degree to which shared risk factors explain the relationship of periodontitis to rheumatoid arthritis (RA) and to determine the associations of PD and Porphyromonas gingivalis with pathologic and clinical features of RA.Abstract:
Periodontitis (PD) has emerged as a risk factor in a number of health conditions including rheumatoid arthritis (RA) (1). Sharing both morphologic and histopathologic similarities with RA (2), PD is an inflammatory disease initiated by bacterial infection resulting in soft and hard tissue destruction and ultimately leading to tooth loss. In addition to shared inflammatory pathways, PD and RA share risk factors for susceptibility and progression, most notably cigarette smoking and, possibly, shared epitope-containing HLA-DRB1 alleles, the latter associated with localized aggressive periodontitis (3–10). Although a causal link between these conditions has not been established, several reports have demonstrated an increased PD prevalence in RA patients compared to controls (11–18).
Growing evidence suggests that pathogens associated with PD could play a role in RA propagation. Chief among the organisms of interest is Porphyromonas gingivalis (P. gingivalis) (19). P. gingivalis is the only known pathogen expressing peptidylarginine deiminase (PPAD). Similar to its human counterpart, P. gingivalis-expressed PAD catalyzes the citrullination of arginine-containing peptides. This is noteworthy because citrullinated antigens are thought to drive adaptive immune responses that are nearly exclusive to RA. The potential role of P. gingivalis in RA pathogenesis has been borne out in epidemiologic investigations. Concentrations of circulating antibody to P. gingivalis have been demonstrated to be associated with the expression of anti-citrullinated peptide antibody (ACPA) (20–22). More recently, our group has shown that antibody to P. gingivalis is associated with the presence of RA-related autoantibody (a combination of rheumatoid factor [RF] and/or ACPA) among individuals at increased risk for disease but who have not yet developed RA symptoms (23), underscoring the potential role of this pathogen in RA development.
As part of the present study, we conducted a large case-control investigation to examine the relationship of PD with established RA. We sought to examine the degree to which this relationship is impacted by shared genetic and/or environmental factors. We also sought to elucidate the degree to which the relationship of PD with RA may be related to infection and/or colonization with P. gingivalis. By using a rigorously selected control population, we attempted to mitigate issues of bias or unmeasured confounding that may have impacted other efforts often using healthy volunteers as comparators (16–18). Finally, using a multiplex approach, we examined the associations of PD and P. gingivalis with autoreactivity to several citrullinated autoantigens that have been implicated in RA disease pathogenesis.read more
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Periodontitis: from microbial immune subversion to systemic inflammation
TL;DR: The mechanisms of microbial immune subversion that tip the balance from homeostasis to disease in oral or extra-oral sites are discussed.
Journal ArticleDOI
Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities
TL;DR: The potential causal link between periodontitis and its comorbidities is further strengthened by recent experimental animal studies establishing biologically plausible and clinically consistent mechanisms whereby periodsontitis could initiate or aggravate a comorbi condition as discussed by the authors.
Journal ArticleDOI
Mechanisms of human autoimmunity
TL;DR: Research in humans and experimental animal models is revealing the genetic and environmental factors that contribute to autoimmunity and strategies for reestablishing the normal balance between effector and regulatory immune responses.
Journal ArticleDOI
The case for periodontitis in the pathogenesis of rheumatoid arthritis
TL;DR: The clinical and experimental evidence supporting the new paradigm of citrullinated epitopes recognized by anti-citrullination protein antibodies is discussed and the potential mechanisms involved in linking periodontitis to RA are presented.
Journal ArticleDOI
Evidence of the Immune Relevance of Prevotella copri, a Gut Microbe, in Patients With Rheumatoid Arthritis.
Annalisa Pianta,Sheila L. Arvikar,Klemen Strle,Elise E. Drouin,Qi Wang,Catherine E. Costello,Allen C. Steere +6 more
TL;DR: Prevotella copri, an intestinal microbe, may overexpand in stool samples from patients with new‐onset rheumatoid arthritis (RA), but it is not yet clear whether the organism has immune relevance in RA pathogenesis.
References
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The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.
Frank C. Arnett,Steven M. Edworthy,Daniel A. Bloch,Dennis J. McShane,James F. Fries,Norman S. Cooper,L. A. Healey,Stephen R. Kaplan,Matthew H. Liang,Harvinder S. Luthra,Thomas A. Medsger,Donald M. Mitchell,David H. Neustadt,Robert S. Pinals,Jane G. Schaller,John T. Sharp,Ronald L. Wilder,Gene G. Hunder +17 more
TL;DR: The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA).
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Significance analysis of microarrays applied to the ionizing radiation response
TL;DR: A method that assigns a score to each gene on the basis of change in gene expression relative to the standard deviation of repeated measurements is described, suggesting that this repair pathway for UV-damaged DNA might play a previously unrecognized role in repairing DNA damaged by ionizing radiation.
Journal Article
Revised criteria for the classification of rheumatoid arthritis.
TL;DR: The Bulletin on the Rheumatic Diseases has published all of the classification criteria for the rheumatic diseases to date, and these new revised classified criteria for rheumatoid arthritis are very important as they should provide understanding of the possibly changing face of rheumatism.
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Revised criteria for the classification of rheumatoid arthritis.
TL;DR: The Bulletin on the Rheumatic Diseases has published all of the classification criteria for rheumatic diseases to date as mentioned in this paper, and these new revised classification criteria are very important as they should provide understanding of the possibly changing face of rheumatoid arthritis.
Journal ArticleDOI
Modified disease activity scores that include twenty-eight-joint counts : development and validation in a prospective longitudinal study of patients with rheumatoid arthritis
M.L.L. Prevoo,M.A. van 't Hof,H.H. Kuper,M.A. van Leeuwen,L. B. A. Van De Putte,P.L.C.M. van Riel +5 more
TL;DR: The Modified DAS that included 28-joint counts were able to discriminate between high and low disease activity (as indicated by clinical decisions of rheumatologists) and are as valid as disease activity scores that include more comprehensive joint counts.