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ID PMID Title PublicationDate abstract
20681888 Adherence to biologic DMARD therapies in rheumatoid arthritis. 2010 Sep IMPORTANCE OF THE FIELD: The efficacy of the biologic disease-modifying antirheumatic drugs (DMARDs) shown in clinical trials may be jeopardized due to prevalent poor patient adherence. AREAS COVERED IN THIS REVIEW: Patient adherence including compliance and persistence with biologic DMARDs in rheumatoid arthritis. WHAT THE READER WILL GAIN: This is a comprehensive review of the literature. The various definitions and methodologies of measurement used in adherence research are reviewed and data are presented by separating compliance and persistence. Differences in compliance rates were mainly based on numerical trends. There was evidence for and against greater persistence with infliximab versus adalimumab and etanercept. There was a trend in favour of greater compliance and lower persistence with TNF-alpha inhibitor monotherapy versus in combination therapy with methotrexate. TAKE HOME MESSAGE: The evidence suggests that adherence to biologic DMARDs is suboptimal. When further research is applied in the field, agreed definitions and methodology need to be used to allow for cross-study comparisons. In addition, adherence should be assessed in conjunction with clinical outcomes and not on its own so that it can be better understood what levels of adherence provide the required clinical outcomes.
19149631 Mesenchymal stromal cells in rheumatoid arthritis: biological properties and clinical appl 2009 Jan Mesenchymal stromal cells (MSC) isolated from a variety of adult tissues including the bone marrow (BM), have the capacity to differentiate into different cell types such as bone and cartilage and have therefore attracted scientific interest as potential therapeutic tools for tissue repair. MSC display also immunosuppressive and anti-inflammatory properties and their putative therapeutic role in a variety of inflammatory autoimmune diseases is currently under investigation. Joint destruction, caused by persistent inflammation, renders rheumatoid arthritis (RA) a possible clinical target for cartilage and bone repair using BM MSCs for their tissue repair and immunoregulatory effects. A number of studies, based mainly on experimental animal models, have recently provided interesting data on the potential of BM-MSCs to suppress local inflammation and tissue damage in RA whereas tissue engineering and cell-scaffold technology represents an emerging field of research. This review deals with the biological repair/regeneration of joint tissues in RA via MSC-based therapies. In view of the current interest in the autologous usage of BM MSC in RA, all available data on the biological properties of patient MSCs including the immunoregulatory characteristics, differentiation capacity towards osteocytes/chondrocytes, clonogenic/proliferative potential and molecular/protein profile and the possible influence of the RA milieu will be also summarized.
19808134 Efficacy of roxithromycin in adult patients with rheumatoid arthritis who had not received 2009 Aug BACKGROUND: It has been reported that antibodies to oral anaerobic bacteria are elevated in the serum and synovial fluids of patients with rheumatoid arthritis. Macrolide antibiotics are active against oral anaerobic bacteria. OBJECTIVE: The aim of this work was to evaluate the clinical efficacy of roxithromycin in patients with early seropositive rheumatoid arthritis. METHODS: This was a double-blind trial. We enrolled adult patients with early rheumatoid arthritis who had not previously received disease-modifying antirheumatic drugs and randomized them to receive either once-daily oral roxithromycin 300 mg or once-daily oral placebo for 3 months. The primary efficacy variable was the percentage of patients who had a 20% improvement according to the American College of Rheumatology (ACR) criteria (an ACR 20 response) at 3 months. Secondary outcome measures were 50% improvement and 70% improvement according to ACR criteria (an ACR 50 response and an ACR 70 response, respectively). The 28-joint disease activity score (DAS28) was also calculated. Clinical remission was defined as DAS28 score <2.6, and a low level of disease activity was defined as DAS28 score <3.2 but > or =2.6. Adverse event data (eg, example, type, severity, time of occurrence, time to resolution) were obtained from physical examinations and patient self-reporting. RESULTS: The roxithromycin group had 16 patients (mean [SD] age, 45 [4] years; 11 women, 5 men; all white). The placebo group had 15 patients (mean [SD] age, 42 [5] years; 10 women, 5 men; all white). A significantly greater percentage of patients treated with 300 mg of roxithromycin experienced an ACR 20 re- sponse at 3 months, compared with those who received placebo (75% [n = 12] vs 20% [n = 3]; P = 0.002). Greater percentages of patients treated with 300 mg of roxithromycin also achieved ACR 50 responses (56% [n = 9] vs 7% [n = 1]; P = 0.003) and ACR 70 responses (44% [n = 7] vs 0%; P = 0.004) compared with patients who received placebo. At month 3, DAS28 response rates were significantly greater with once-daily roxithromycin 300 mg than with once-daily placebo (P < 0.001). Adverse events were reported for 11 patients (69%) in the roxithromycin group and 7 patients (47%) in the placebo group. The most common adverse events (>5%) were nausea, abdominal pain, headache, and dry mouth. There were no dose-limiting toxic effects. One participant in the roxithromycin group withdrew from the study because of severe emesis; two withdrew from the placebo group because of lack of efficacy. CONCLUSIONS: In these adult patients with rheumatoid arthritis, 3-month treatment with roxithromycin significantly improved the signs and symptoms of rheumatoid arthritis and was generally well tolerated. Future studies should investigate the relationship between disease activity and serum or joint antibodies to anaerobic bacteria.
19351317 "My foot hurts": a flare of rheumatoid arthritis? 2009 Apr 6 A 56-year-old man with a history of rheumatoid arthritis presented with a 2-day history of worsening pain in his left foot. Treatment with high-dose steroids was of no benefit, hence a diagnosis of septic arthritis was considered. However, the patient's condition deteriorated despite empirical antibiotic therapy. Following persistent investigation, the cause was identified as a fastidious Legionella longbeachae infection, and appropriate antibiotic therapy led to complete resolution of the sepsis. This emphasises the importance of considering infections with atypical organisms in patients on immunosuppressive therapy.
19734737 Rapid recurrence of a giant popliteal cyst in a patient with rheumatoid arthritis. 2009 Sep Despite increasing knowledge of etiopathogenesis, therapy, and recurrence rate of popliteal cysts, they nevertheless occasionally represent clinical problems. We report the case of a 58-year-old rheumatoid arthritis patient in whom a giant recurrent cyst developed very shortly after primary excision. Reports of such large popliteal cysts are rare and very few cases were reported in rheumatoid arthritis patients. Moreover, no such giant recurrent cysts formed so shortly after primary excision. Thus, its occurrence may be partially ascribed to the specific dynamics of fluid flows caused by the absence of a valve-like mechanism. With regard to treatment, it appears that synovectomy may reduce the production of synovial fluid, but reinforcement of the thin tissue with capsuloplasty may also be important. Immobilization is necessary so that initiation of the healing process is not disturbed.
20969554 Anti-interleukin-6 therapy in rheumatoid arthritis. 2010 Recent advances in research have led to significant progress in unraveling the pathophysiology of rheumatoid arthritis (RA), including the cytokine-mediated signaling process. While therapies targeting one particular cytokine, tumor necrosis factor-alpha (TNF-α), have revolutionized the treatment of RA, other cytokines, including interleukin 6 (IL-6,) have been implicated in the disease process. In this review, we describe the research that ultimately led to large, randomized, controlled trials demonstrating the effectiveness of tocilizumab, a monoclonal antibody directed against the IL-6 receptor, as a potent new therapeutic agent in RA treatment. These data have shown this agent to be effective both in patients failing non-biologic DMARDs and those failing anti-TNF therapy, although the drug is currently approved for use only in the latter situation. Adverse events seen with tocilizumab therapy are also reviewed.
20937307 Global DNA methylation, DNMT1, and MBD2 in patients with rheumatoid arthritis. 2011 Mar 30 OBJECTIVES: To investigate the associations of DNA methylation levels and mRNA expressions of DNA cytosine-5-methyltransferase 1 (DNMT1) and methyl CpG-binding domain 2 (MBD2) with rheumatoid arthritis (RA). METHODS: The global methylation status of DNA was measured in 65 patients with RA and 64 healthy controls by the ELISA method. DNMT1 and MBD2 mRNA were also detected in 177 RA patients and 95 controls using the quantitative real-time polymerase chain reaction method. RESULTS: The global methylation of DNA was significantly decreased in the RA patients compared to the controls (p=0.005, 95% CI=0.0835-0.4503). The patients with RA had higher expressions of DNMT1 and MBD2 mRNA than the controls (p<0.001, 95% CI=-0.0024 to -0.0053 and p<0.001, 95% CI=-0.0079 to -0.0167, respectively). We also found that the MBD2 mRNA level was not related to the disease activity of RA. However, the expression of DNMT1 mRNA tended to be associated with the disease activity of RA (p=0.08). The levels of DNA methylation and DNMT1 mRNA were significantly decreased in the patients with anti-CCP antibody compared with those without (p=0.005, 95% CI=-0.7333 to -0.1373 and p=0.003, 95% CI=-0.0071 to -0.0022, respectively). The differences in the methylation level and expressions of DNMT1 and MBD2 were not significant between the patients treated with and without anti-TNFα biological agents (Enbrel or Humira). CONCLUSION: This study demonstrated that the RA patients have a significantly lower level of DNA methylation than the controls. Moreover, RA patients have higher expressions of DNMT1 and MBD2 mRNA. The anti-TNFα biological agents do not seem to affect DNA methylation and mRNA expressions of DNMT1 and MBD2 in RA patients.
20421343 Efficacy of initial methotrexate monotherapy versus combination therapy with a biological 2010 Jul OBJECTIVE: The target outcome in early rheumatoid arthritis (ERA) is now remission. This meta-analysis compared the efficacy of initial methotrexate monotherapy versus combination therapy (methotrexate plus biological agent) for clinical remission and radiographic non-progression among ERA patients with minimal or no previous methotrexate exposure. METHODS: A systematic search was performed for randomised controlled trials of ERA using predefined criteria. A random effects model was used to pool the risk ratio (RR) for clinical and radiographic remission at 52-56 weeks of follow-up. RESULTS: Seven trials of combination therapy with infliximab, adalimumab, etanercept or abatacept were included. The majority of studies defined clinical remission as a 28-joint disease activity score (DAS28) of 2.6 or less. Radiographic non-progression was primarily defined as a modified total Sharp score change of less than 0.5 units. All trials demonstrated risk estimates in favour of combination therapy: the pooled RR for achieving clinical remission was 1.74 (95% CI 1.54 to 1.98) and for radiographic non-progression was 1.30 (95% CI 1.01 to 1.68). Significant heterogeneity among studies for the latter outcome was detected (p<0.001). CONCLUSIONS: The efficacy of combination therapy with a biological agent is superior to methotrexate monotherapy for remission. Combination therapy has a greater initial effect on clinical remission than radiographic non-progression. Uniform definitions of remission are needed and the proportion of subjects who achieve the combined endpoint of clinical and radiographic remission should be considered as a meaningful outcome in future studies of ERA.
19672900 A clinical perspective of rheumatoid arthritis. 2009 Aug In recent years, factors potentially involved in pathogenesis of rheumatoid arthritis have mostly been identified by studying well-defined patient cohorts. Characterization of antibodies from sera of affected patients, family-based heritability studies, genome-wide association scans, the analysis of environmental factors and data from clinical trials have contributed largely to a thorough reassembly of our perception of rheumatoid arthritis. Modified animal models are now crucial to obtain experimental evidence for suggested pathogenetic pathways based on these observations and are currently being developed and explored. Some of the novel pathogenetic aspects, however, already influence decision making in the clinic.
21037562 Clinical trials: Tight control in early RA pays off in the long run. 2010 Nov Clinical trials demonstrate that intensive treatment of early rheumatoid arthritis with a combination of DMARDs improves short-term outcomes. an extension study from a pivotal trial has now shown that such intensive early therapy can achieve a reduction in the rate of erosive progression over a period of 11 years.
20110521 Mortality and predictors of mortality in rheumatoid arthritis--a role for mannose-binding 2010 Mar OBJECTIVE: Patients with rheumatoid arthritis (RA) have increased overall and cardiovascular mortality. Mannose-binding lectin (MBL) may play differentiated roles in the pathogenesis of RA. We had observed that high serum levels of MBL increased the risk of ischemic heart disease in patients with RA. In this followup study we describe the mortality in a cohort of 229 Danish patients with RA. We examine if previously reported factors and MBL influence the risk of overall death and death due to cardiovascular disease. METHODS: Known predictors of RA mortality were assessed. MBL extended genotypes (YA/YA, YA/XA, XA/XA, YA/YO, XA/YO, YO/YO) were determined; MBL serum concentrations were measured. The vital status and causes of death were assessed in a prospective study. RESULTS: The median followup was 10.3 years. The overall risk of death was 4% per year. Comparing mortality in the RA cohort with mortality in an age- and sex-matched cohort based on the general Danish population, we found significantly increased overall mortality [standardized mortality ratio (SMR) 1.5, 95% CI 1.2-1.9, and cardiovascular mortality (SMR 1.7, 95% CI 1.3-2.6)]. In multivariate analysis, significant predictors of overall death were extraarticular manifestations, positive rheumatoid factor, increased C-reactive protein (CRP), poor nutritional state, and serum MBL. Predictors of cardiovascular death were Health Assessment Questionnaire score, increased CRP, poor nutritional state, and the high-producing MBL genotype YA/YA. CONCLUSION: Both overall and cardiovascular mortality were increased in Danish patients with RA. In our cohort, states of high MBL production and several previously reported factors contributed significantly to this increased risk of overall death and cardiovascular death.
20974296 The CC homozygosis of the -174G>C IL-6 polymorphism predicts a lower efficacy of rituximab 2012 Mar Identification of genetic biomarkers of response to biologics in rheumatoid arthritis (RA) is a relevant issue. Being IL-6 a key cytokine for B cell survival, the interleukin-6 (IL-6) -174G>C and the IL-6 receptor (IL-6R) D358A gene polymorphisms were investigated in 158 RA patients treated with rituximab (RTX). One hundred and twenty-eight (81.0%) were RF positive and 126 (79.7%) were anti-CCP positive. Response to therapy was evaluated at the end of the sixth month after the first RTX infusion, by using both the EULAR and the ACR criteria. The possible relationship with IL-6 serum levels was also studied. By univariate analysis, lack of response by the EULAR criteria was more prevalent in RA patients with the IL-6 -174 CC genotypes (39.1%), than in the GC/GG patients (18.5%) (OR 2.83; 95%CI=1.10-7.27; p=0.031). A good response was noticed in only one patient (4.3%) with the IL-6 -174 CC genotype, while it was present in 24.4% of GG/GC cases (p=0.06). By stepwise multivariate analysis (including RA duration, baseline DAS28, baseline HAQ, RF status, anti-CCP status and IL-6 genotype as covariates), the IL-6 -174CC genotype was selected as an independent predictor of no response to RTX by both EULAR and ACR≥50 criteria, while the IL-6R polymorphism resulted as not associated. No definite association between gene polymorphisms and IL-6 serum levels was noticed. Present results suggest a possible role for IL-6 genotyping to better plan treatment with RTX in RA, and larger studies are worthwhile.
20451437 Infections induced by low-dose corticosteroids in rheumatoid arthritis: a systematic liter 2010 May OBJECTIVE: To study the association between infection risk and low-dose corticosteroids (LD-CT, defined as a daily dose <10mg/day of prednisone) in rheumatoid arthritis (RA). DATA SOURCE: a systematic review of the literature up to June 2009 was performed. Data extraction :all type of infections: bacterial, viral and postoperative; infection severity, RA activity, RA severity, comorbid conditions. DATA ANALYSIS: descriptive, comparing infection risk between LD-CT-treated and LD-CT-not treated RA. RESULTS: Of the 1310 screened reports, the literature analysis identified 15 assessing infection risk of LD-CT in RA patients. Of the eight reports that studied all types of infection, six articles found no association between risk of infection and LD-CT, one showed an association between severe infections and LD-CT (OR=8 [1-64]) and another showed a dose-dependent association including doses of less than 5mg/day: RR=1.32 [1.06-1.63] and doses between 6 to 10mg/day: RR=1.95 [1.53-2.46]. Of the three trials that studied infection risk secondary to bacteria, one showed an increased risk (HR=1.7 [1.5-2.0]) while two did not (respectively, exposure to <5mg/day: OR=1.34 [0.85-2.13]; 6 to 9mg/day: OR=1.53 [0.95-2.48] and <5mg/day: OR=1.49 [0.82-2.72]; 5 to 10mg/day: OR=1.46 [0.84-2.54]). None of the three trials studying postoperative infection risk found any association between infection risk and LD-CT treatment. Two reports studied herpes zoster risk and found no association with LD-CT. CONCLUSION: There was a paucity of data about LD-CT and infection risk in RA and that risk seems poorly increased. These findings need to be confirmed by further studies.
20001643 Living with rheumatoid arthritis and experiencing everyday life with TNF-α blockers. 2010 Dec The aim of this study was to describe how persons with RA from an area in western Sweden experience everyday life with TNF-α blockers. A purposive sampling of 11 women and four men, with an age ranging from 25 to 70 years, was conducted. A phenomenological approach was used in the study. The data were collected by unstructured in-depth interviews. The data analysis resulted in six code groups, of which four have appurtenant sub-groups. The six code groups are: "A noticeable change dominates the picture"; "Change in bodily and mental symptoms enables activity"; "Enabling care for oneself and others"; "Enabling improved or continued productivity"; "More rewarding leisure time"; and "Drawbacks of the medication". The findings show that most of the informants had experienced dramatic changes in their daily lives since the medication reduced their symptoms, resulting in an increased level of activity.
19037610 The comparison of ultrasonographic and scintigraphic findings of early arthritis in reveal 2009 May We aimed to investigate the diagnostic significance of high frequency ultrasonography (USG), comparing the findings in USG, bone scintigraphy and clinical stuation. Fifty-one patients who had early symptoms of inflammatory arthritis, but not fulfilling the ACR diagnostic criteria for rheumatoid arthritis (RA) were included in this study. They were referred to USG and bone scintigraphy for examination of the synovial joints. After following at least 2 years with visits at every 3 months, those who fulfilled the ACR criteria for the diagnosis of RA were defined as reference group. The concordance levels were assessed with Kappa statistic among them. The diagnosis of inflammatory arthritis that was made with USG in early time showed average agreement with the diagnosis according to ACR criteria. However, there was statistically discordance between the diagnosis of inflammatory arthritis that was made with bone scintigraphy in early time and the diagnosis according to ACR criteria.
18375540 Changes in hand and generalised bone mineral density in patients with recent-onset rheumat 2009 Mar OBJECTIVES: To evaluate changes in bone mineral density (BMD) in the hands, hip and spine after 1 and 2 years of follow-up, in relation to antirheumatic and antiresorptive therapies and disease and demographic variables in patients with recent-onset rheumatoid arthritis (RA). METHODS: Changes in BMD measured in metacarpals 2-4 by digital x-ray radiogrammetry and in the hip and spine by dual energy x-ray absorptiometry were assessed at baseline and after 1 and 2 years of follow-up in 218 patients with recent-onset RA from the BeSt study, who received one of four treatment strategies: sequential monotherapy (group 1); step-up combination therapy (group 2); initial combination therapy with tapered high-dose prednisone (group 3); or initial combination therapy with infliximab (group 4). RESULTS: After 1 and 2 years, there was significant BMD loss in all locations, with significantly greater BMD loss in the hands than generalised BMD loss in the hip and spine. Initial combination therapy with prednisone or infliximab were associated with less hand BMD loss compared with initial monotherapy after 1 and 2 years (-0.9 and -1.6%, -0.6 and -1.4%, -1.7 and -3.3%, and -2.6 and -3.6% for group 4-1 after 1 and 2 years, overall p = 0.001 and p = 0.014, respectively). Progression in erosions was independently associated with increased BMD loss both in the hands and hip after 1 year. The use of bisphosphonates protected only against generalised BMD loss in the hip and spine. CONCLUSIONS: The association between joint damage progression and both hand and generalised BMD loss in RA suggests common pathways between these processes, with hand BMD loss occurring earlier in the disease course than generalised BMD loss.
19193698 Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis pati 2009 Jun OBJECTIVES: We examined the association between candidate single nucleotide polymorphisms (SNPs) and disease activity in RA patients on MTX. METHODS: Our population was drawn from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS), a prospective, observational cohort of RA patients. A total of 556 participants were genotyped using the Affymetrix 100K platform. Two hundred and sixty-two participants were on MTX therapy, including 120 on MTX monotherapy. The primary outcome was the disease activity score in 28 joints (DAS28-CRP). High disease activity was defined as DAS28-CRP >3.2. Low disease activity was defined as DAS28-CRP < or =3.2. We studied three candidate alleles in the ATIC, ITPA and MTHFR genes for association with DAS28-CRP. RESULTS: Among participants on MTX monotherapy, those carrying the minor allele of ATIC SNP rs4673993 were more likely to have low disease activity (P = 0.01). None of the other SNPs was associated with disease activity. Among patients on any MTX (combination or monotherapy), the minor allele of ATIC rs4673993 was also associated with low disease activity (P = 0.04). CONCLUSIONS: In this cross-sectional analysis, ATIC SNP rs4673993 was associated with low disease activity in patients on MTX. Further studies are needed to clarify the relationship between ATIC polymorphisms, disease activity and treatment response.
20586922 Blood-induced joint disease: the pathophysiology of hemophilic arthropathy. 2010 Sep Arthropathy is a frequent and serious complication of repeated joint bleeding in patients with hemophilia, resulting in pain, deformity, and disability. Although the pathogenesis of hemophilic arthropathy has not been fully elucidated, it appears to have similarities with the degenerative joint damage that occurs in osteoarthritis and the inflammatory processes associated with rheumatoid arthritis. This article reviews the potential actions of various blood constituents on joint components that culminate in the development of hemophilic arthropathy.
19117726 Familial disease, the HLA-DRB1 shared epitope and anti-CCP antibodies influence time at ap 2009 Feb Rheumatoid arthritis (RA) progresses more rapidly in some patients than in others and diverse factors influence radiographic progression in a specific population. Thus, we searched for variables that are associated with an early appearance of substantial joint damage in patients with RA by using radiographic assessments. A cohort of 157 consecutively enrolled Colombian RA patients was followed for an average of 3.2+/-3.1 years. Information on patient demographics and cumulative clinical and laboratory manifestations over the course of the disease was registered, including family history of RA in first-degree relatives, extra-articular manifestations, rheumatoid factor, anti-CCP3 antibodies, TNF single nucleotide polymorphism at -308 position, and HLA-DRB1 status. Radiographs were scored according to the Sharp-van der Heijde method. Survival analyses of the time at appearance of substantial joint damage were performed by using Weibull models. A review of literature about the influence of familial RA on the progression of disease was done. Our results show that family history of RA is consistently associated with joint damage (i.e. erosive and joint narrowing disease). This effect was not found in all the populations reviewed. In addition, we confirm the effect of HLA-DRB1 shared epitope and anti-CCP seropositivity on erosive disease. Family history of RA is a key risk factor for joint damage and depends on the investigated population because variations in both additive and non-additive genetic factors and the environmental variance are specific to the population. Our results emphasize the usefulness of assessing familial disease, testing anti-CCP antibodies and genotyping HLA-DRB1 gene in patients with RA because these factors may be used to predict clinical outcomes and guide therapeutic interventions.
19246161 Porphyromonas gingivalis may play an important role in the pathogenesis of periodontitis-a 2009 Jun Rheumatoid arthritis (RA) is a common, systemic autoimmune disease which leads to destruction of the joint architecture and consequent disability. Although the aetiology of RA remains unknown, accumulating studies have established a strong association between RA and periodontitis (PD). Recently, anti-cyclic citrullinated peptide (anti-CCP) autoantibody and citrullinated peptide have been realized to be involved in the breaking of self-tolerance and development of autoimmune in RA. The citrullinated peptide is generated by post-translational modification (citrullination) of protein-bound arginine by peptidylarginine deiminase (PAD). Porphyromonas gingivalis(P. gingivalis), the major aetiological agent of PD and the only bacterium known to express a PAD enzyme, has been reported to be significantly associated with RA. The antibody titers to P. gingivalis are significantly increased in patients with RA and P. gingivalis antibody titers are significantly correlated with anti-CCP antibody isotypes that are specific to RA. Recent study indicates that the major synovial targets of the RA-specific anti-CCP autoantibodies are deiminated forms of the alpha- and beta- chains of fibrin. Meanwhile, it is also confirmed that bacterial PAD produced by P. gingivalis has the capacity of deiminating arginine in fibrin found in the periodontal lesion. What's more, it has been demonstrated that citrullination of HLA binding peptide causes a 100-fold increase in peptide-MHC affinity and leads to the activation CD4(+)T cells in HLA DRB1 0401 transgenic mice. Therefore, we postulate that P. gingivalis may play a crucial role in the pathogenesis of periodontitis-associated RA. P. gingivalis, which colonizes in the oral cavity, produces PAD enzyme continuously that leads to the citrullination of RA autoantigen such as fibrin in synovium joint. These PAD engendered antigens, presented in association with major histocompatibility complex (MHC) molecules by antigen-presenting cells (APC), ultimately lead to production of the anti-CCP antibody. The anti-CCP antibodies form immune complexes with citrullinated proteins, which can be bound by inflammatory cells via their Fc receptors. The roles of these immune complexes and inflammatory cells are mediated by a complex cascade involving complement activation. These mechanisms result in a release of mediators of inflammation and joint destruction ultimately leading to the onset of RA. This hypothesis reveals that oral bacterial infection may play a role in peptide citrullination which might be involved in loss of self-tolerance and development of autoimmune in RA.