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 A retrospective cohort study of cigarette smoking and risk of rheumatoid arthritis in female health professionals. Effects of periodontal therapy on disease activity and systemic inflammation in rheumatoid arthritis patients. DNA probe analyses of the survival of selected periodontal pathogens following scaling, root planing, and intra-pocket irrigation. Assessment of the Plasma/Serum IgG Test to Screen for Periodontitis Serum antibodies to oral anaerobic bacteria in patients with rheumatoid arthritis. Persistent Periodontal Disease Hampers Anti–Tumor Necrosis Factor Treatment Response in Rheumatoid Arthritis Periodontal treatment decreases levels of antibodies to Porphyromonas gingivalis and citrulline in patients with rheumatoid arthritis and periodontitis. Expression of anti-Porphyromonas gingivalis peptidylarginine deiminase immunoglobulin G and peptidylarginine deiminase-4 in patients with rheumatoid arthritis and periodontitis.
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 aim ed to study the relation of these factors to the risk of RA in a prospect i ve cohort . Methods We performed a nested case – control study by identifying pre-RA cases in four population s from the European Prospect i ve Investigation into Cancer and nutrition , matched with three controls . Data on smoking and other covariates were obtained from baseline question naires . 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 vali date d 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 OBJECTIVE To study the association of cigarette smoking with risk of  rheumatoid arthritis ( RA ) , among 377,481 female health professionals in the Women 's Health Cohort Study . METHODS Subjects completed mailed question naires regarding demographics , health habits , including cigarette smoking history , and medical history , including RA diagnosis made by a physician and date of diagnosis . Of 7,697 women who self-reported RA , 3,416 reported seropositive RA . Cox proportional hazards regression models were used to retrospectively assess the associations of smoking intensity and duration with the risk of developing RA or seropositive RA . Cigarette smoking status was treated as a time-varying exposure in these regression models . RESULTS In multivariate analyses controlling for age , race , education , age at menarche , pregnancy history , menopausal status , and postmenopausal hormone use , duration of smoking was associated with a significantly increased risk of both RA and seropositive RA ( both P < 0.01 for trend ) , after adjusting for smoking intensity . Women who smoked > or = 25 cigarettes/day for more than 20 years experienced a 39 % increased risk of RA and 49 % increased risk of seropositive RA . However , smoking intensity ( number of cigarettes/day ) was unrelated to risk of RA or seropositive RA ( both P = 0.3 for trend ) , after adjusting for duration of smoking . CONCLUSION Duration , but not intensity , of cigarette smoking is associated with a modest increased risk of RA in women OBJECTIVE This observational prospect i ve cohort study aim ed to evaluate the effects of non-surgical periodontal treatment on clinical periodontal measurements and systemic inflammatory mediator levels in low or moderate to highly active rheumatoid arthritis ( RA ) patients with chronic periodontitis . SUBJECTS AND METHODS Rheumatoid arthritis activity was assessed with disease activity score test ( DAS28 ) . Thirty patients with RA with moderate to high disease activity ( DAS28 ≥ 3.2 ) and chronic periodontitis ( MHDA group ) and thirty patients with RA with low disease activity ( DAS28 < 3.2 ) and chronic periodontitis ( LDA group ) were enrolled in the study . The patients were monitored at the beginning and 3 months after undergoing periodontal therapy . Erythrocyte sedimentation rate ( ESR ) , C-reactive protein ( CRP ) , tumour necrosis factor-alpha ( TNF-α ) levels in serum , DAS28 and periodontal parameters were evaluated . RESULTS Erythrocyte sedimentation rate , CRP , TNF-α levels in serum , DAS28 and periodontal parameters exhibited similar and significant reduction 3 months after the non-surgical periodontal treatment . CONCLUSION Non-surgical periodontal treatment may prove beneficial in reducing RA severity as measured by ESR , CRP , TNF-α levels in serum and DAS28 in low or moderate to highly active RA patients with chronic periodontitis This clinical study evaluated the survival rates of Actinobacillus actinomycetemcomitans , Porphyromonas gingivalis , and Prevotella intermedia in periodontal pockets following scaling and root planing and intra-pocket irrigation with antimicrobial agents in patients with moderate and severe periodontitis . The number of target organisms was determined utilizing DNA probes . Adult periodontitis patients were selected on the basis that the subgingival flora contained at least one of the target organisms . Forty-eight ( 48 ) inflamed pockets > or = 5 mm in depth with probing attachment loss and containing at least one of the target species were then selected in 7 adult patients who harbored these bacteria . Following baseline clinical and bacterial examination , all patients received thorough scaling and root planing . In addition , 1 or 2 teeth in each patient which harbored the target flora at baseline were r and omly assigned to each of the following 4 treatment modalities : 1 ) control group , no irrigation ; 2 ) saline group , irrigation with 2 cc of physiologic saline ; 3 ) tetracycline group , irrigation with 2 cc of aqueous tetracycline hydrochloride , 50 mg/ml ( 5 % ) ; and 4 ) chlorhexidine group , irrigation with 2 cc 0.12 % chlorhexidine . All selected sites ( 5 to 8 per patient ) were nonadjacent teeth . Clinical parameters and microbial analysis were recorded again at one week , and one month post-irrigation . The survival rate of the target microorganisms was determined and the effect of irrigation with antimicrobial agents on this microflora was compared with the control groups ( 1 and 2 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Chronic periodontitis is a silent infectious disease prevalent worldwide and affects lifestyle-related diseases . Therefore , efficient screening of patients is essential for general health . This study was performed to evaluate prospect ively the diagnostic utility of a blood IgG antibody titer test against periodontal pathogens . Oral examination was performed , and IgG titers  against periodontal pathogens were measured by ELISA in 1,387 individuals . The cut-off value of the IgG titer was determined in receiver operating characteristic curve analysis , and changes in periodontal clinical parameters and IgG titers by periodontal treatment were evaluated . The relationships between IgG titers and severity of periodontitis were analyzed . The best cut-off value of IgG titer against Porphyromonas gingivalis for screening periodontitis was 1.682 . Both clinical parameters and IgG titers decreased significantly under periodontal treatment . IgG titers of periodontitis patients were significantly higher than those of healthy controls , especially in those with sites of probing pocket depth over 4 mm . Multiplied cut-off values were useful to select patients with severe periodontitis . A blood IgG antibody titer test for Porphyromonas gingivalis is useful to screen hitherto chronic periodontitis patients ( Clinical Trials.gov number NCT01658475 ) BACKGROUND This study was conducted to determine the component that causes the disease in rheumatoid arthritis ( RA ) , which shows great resemblance to periodontitis in a pathologic context . MATERIAL S AND METHODS Within this study , the pathogen-specific IgG levels formed against Porphyromonas gingivalis FDC 381 , Prevotella melaninogenica ATCC 25845 , Actinobacillus actinomycetemcomitans Y4 , Bacteroides forsythus ATCC 43047 , and Prevotella intermedia 25611 oral bacteria were research ed from the blood serum sample s of 30 RA patients and 20 healthy controls with the enzyme-linked immunosorbent assay ( ELISA ) method . RESULTS The IgG levels of P gingivalis , P intermedia , P melaninogenica , and B forsythus were found to be significantly higher in RA patients when compared with those of the controls . Of the other bacteria antibodies , A actinomycetemcomitans was not found at greater levels in RA serum sample s in comparison with the healthy sample s. CONCLUSION The antibodies formed against P gingivalis , P intermedia , P melaninogenica , and B forsythus could be important to the etiopathogenesis of RA Objective This study aim ed to evaluate prospect ively the influence and the evolution of periodontal disease ( PD ) in rheumatoid arthritis ( RA ) patients su bmi tted to anti – tumor necrosis factor ( TNF ) therapy .  Methods Eighteen patients with RA ( according to the American College of Rheumatology criteria ) were assessed for PD before ( BL ) and after 6 months ( 6 M ) of anti-TNF treatment : 15 infliximab , 2 adalimumab , and 1 etanercept .  Periodontal assessment included plaque and gingival bleeding indices , probing pocket depth , cementoenamel junction , and clinical attachment level . Rheumatologic evaluation was performed blinded to the dentist ’s assessment : demographic data , clinical manifestations , and disease activity ( Disease Activity Score using 28 joints [ DAS28 ] , erythrocyte sedimentation rate [ ESR ] , and C-reactive protein [ CRP ] ) . Results The median age and disease duration of patients with RA were 50 years ( 25–71 y ) and 94 % were female .  Periodontal disease was diagnosed in 8 patients ( 44.4 % ) . Comparing BL to 6 M , periodontal parameters in the entire group remained stable ( P > 0.05 ) throughout the study ( plaque and gingival bleeding indices , probing pocket depth , cementoenamel junction , and clinical attachment level ) , whereas an improvement in most analyzed RA parameters was observed in the same period : DAS28 ( 5.5 vs. 3.9 , P = 0.02 ) , ESR ( 21 vs. 12.5 mm/first hour , P = 0.07 ) , and CRP ( 7.8 vs. 2.8 mg/dL , P = 0.25 ) . Further analysis revealed that this improvement was restricted to the group of patients without PD ( DAS28 [ 5.5 vs. 3.6 , P = 0.04 ] , ESR [ 23.0 vs. 11.5 mm/first hour , P = 0.008 ] , and CRP [ 7.4 vs. 2.1 , P = 0.01 ] ) . In contrast , patients with PD had lack of response , with no significant differences in disease activity parameters between BL and 6 M : DAS28 ( 5.2 vs. 4.4 , P = 0.11 ) , ESR ( 17.0 vs. 21.0 , P = 0.56 ) , and CRP ( 9.0 vs. 8.8 , P = 0.55 ) . Conclusions This study supports the notion that PD may affect TNF blocker efficacy in patients with RA . The possibility that a sustained gingival inflammatory state may hamper treatment response in this disease has high clinical interest because this is a treatable condition BACKGROUND Porphyromonas gingivalis has been implicated as an etiologic agent of rheumatoid arthritis ( RA ) because of the expression of peptidylarginine deiminase . The present study evaluates whether periodontal treatment may affect serum antibodies to P. gingivalis and citrulline levels in relation to disease activity of RA . METHODS Fifty-five patients with RA were r and omly assigned to receive oral hygiene instruction and supragingival scaling ( treatment group , n = 26 ) or no periodontal treatment ( control group , n = 29 ) . Periodontal and rheumatologic parameters and serum levels of cytokine and inflammatory markers citrulline and immunoglobulin (Ig)G to P. gingivalis were examined at baseline and 8 weeks later . RESULTS Both groups did not differ statistically in any parameters except percentage of sites with probing depth and clinical attachment level ≥ 4 mm at baseline . The treatment group exhibited a significantly greater decrease in disease activity score including 28 joints using C-reactive protein ( DAS28-CRP ) ( P = 0.02 ) , serum levels of IgG to P. gingivalis hemin binding protein (HBP)35 ( P = 0.04 ) , and citrulline ( P = 0.02 ) than the control group . Serum levels of IgG to P. gingivalis HBP35 were significantly correlated positively with those of anti-cyclic citrullinated peptide antibodies ( P = 0.0002 ) . The same correlation was obtained between serum levels of IgG to P. gingivalis-sonicated extracts and those of rheumatoid factor ( P = 0.02 ) . CONCLUSIONS These results suggest that supragingival scaling decreases DAS28-CRP and serum levels of IgG to P. gingivalis HBP35 and citrulline in patients with RA . These observations may reflect a role of P. gingivalis in the protein citrullination , which is related to the pathogenesis of RA BACKGROUND AND OBJECTIVE Autoimmunity against citrullinated proteins through peptidylarginine deiminase ( PAD ) may be involved in the pathophysiology of rheumatoid arthritis ( RA ) . The present study evaluated the serum levels of antibodies to citrullinated proteins and to Porphyromonas gingivalis PAD ( PPAD ) , and the endogenous expression of PAD-4 , in individuals with and without RA , as well as before and after periodontal treatment . MATERIAL AND METHODS The study participants consisted of 52 patients with RA ( RA group ) and 26 age- , gender- and smoking status-matched healthy controls ( non-RA group ) . Of the 52 patients , 26 were r and omly assigned to receive oral hygiene instruction and supragingival scaling ( RA subgroup ) . After periodontal and rheumatologic assessment s , the serum levels of anti-cyclic citrullinated peptide ( CCP ) immunoglobulin G ( IgG ) , anti-PPAD IgG and PAD-4 were determined using ELISA . RESULTS The serum levels of anti-CCP IgG and anti-PPAD IgG were significantly higher in the RA group than in the non-RA group ( p < 0.001 and p = 0.03 ) . A significant , positive correlation was observed between the serum levels of anti-PPAD IgG and anti-CCP IgG ( p = 0.04 ) , but not between the serum levels of PAD-4 and anti-CCP IgG. Multiple logistic regression analyses revealed a significant association between anti-PPAD IgG responses and RA after adjustment for age , gender and smoking ( p = 0.004 ) . Supragingival scaling significantly improved the periodontal condition and disease activity of RA ( p < 0.05 ) , but failed to decrease the serum levels of anti-CCP IgG , anti-PPAD IgG and PAD-4 after 2 mo of treatment . CONCLUSION These results might suggest an association between anti-PPAD IgG and anti-CCP IgG responses , implicating a role for PPAD in protein citrullination in patients with RA and periodontitis
Objectives Since the peptidyl arginine deiminase of Porphyromonas gingivalis is able to citrullinate peptides and proteins , various studies have suggested the species as a possible link between periodontal disease ( PD ) and rheumatoid arthritis ( RA ) .
This systematic review including meta- analysis was aim ed to evaluate whether differences in terms of antibody titers against P. gingivalis exist between RA patients and systemically healthy individuals with and without PD .
Material s and methods The following focused question was addressed : Are the antibody titers against P. gingivalis of RA patients different from systemically healthy individuals with and without PD ?