scholarly journals POS1425 ANTIBODIES TO PORPHYROMONAS GINGIVALIS ASSOCIATE WITH THE PRESENCE OF RHEUMATOID ARTHRITIS-RELATED AUTOANTIBODIES IN PATIENTS WITH PERIODONTITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 996.1-996
Author(s):  
C. De Vries ◽  
G. Ruacho ◽  
N. Sippl ◽  
B. A. Potempa ◽  
L. Ryden ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Myocardial Infarction ◽  
Porphyromonas Gingivalis ◽  
Lupus Erythematosus ◽  
Epidemiologic Studies ◽  
Oral Bacteria ◽  
Serological Marker ◽  
Serum Samples ◽  
Increased Risk ◽  
First Myocardial Infarction

Background:Epidemiologic studies have demonstrated a link between periodontitis (PD) and rheumatoid arthritis (RA), specifically RA characterized by anti-citrullinated protein antibodies (ACPA). The keystone pathogen driving PD, Porphyromonas gingivalis (Pg), is the only pathogen known to express peptidylarginine deiminase (PAD), a citrullinating enzyme. Hence, Pg has been proposed to be involved in triggering the ACPA response, by generating citrullinated antigens in an inflammatory milieu(1). Another major virulence factor of Pg is arginine gingipain B (RgpB), a proteinase which cleaves proteins so that P.PAD can access the site where citrullination takes place. We have previously shown elevated anti-RgpB IgG levels in ACPA+ RA patients, even before clinical onset(2, 3), and we hypothesize that anti-RgpB IgG could serve as a serological marker to identify PD patients with increased risk of developing ACPA+ RA.Objectives:Based on this hypothesis, we set out to investigate whether anti-RgpB IgG was associated with PD, PD severity, autoimmunity in general, and the ACPA response in particular.Methods:Anti-RgpB IgG, as well as RA- and systemic lupus erythematosus (SLE)-related autoantibodies targeting cyclic citrullinated peptide(s) (CCP2), rheumatoid factor (RF), dsDNA, cardiolipin, and β2 glycoprotein, were measured by ELISA in serum samples from the ParoKrank study, which is a well-characterized cohort of 805 patients with a first myocardial infarction and 805 matched controls, where periodontal status has been determined by dentists(4). In this study, individuals with PD (n=941) were compared to individuals without PD (n=557).Results:We detected significantly elevated (p<0,0001) anti-RgpB IgG levels in PD compared to non-PD individuals, with highest levels recorded in severe PD. Anti-RgpB IgG levels were significantly increased in PD patients positive for CCP2 and/or RF (n=50), when compared to PD patients negative for CCP2 and RF (n=507), p<0,05, and when compared to non-PD individuals positive for CCP2 and/or RF (n=62), p < 0,05. Notably, these differences were not seen for SLE-related autoantibodies. In addition, anti-RgpB IgG levels were significantly elevated amongst MI patients versus controls (p < 0,05), supporting the previous finding that PD is more common among MI patients(4).Conclusion:Our data demonstrates a specific association between severe PD, elevated anti-RgpB IgG levels and RA-related autoantibodies, supporting a role for Pg in linking PD to ACPA+ RA. Further investigation will be needed to confirm whether anti-RgpB IgG can be used as a serological marker to identify PD patients with increased risk of developing ACPA+ RA.References:[1]Rosenstein ED, Greenwald RA, Kushner LJ, Weissmann G. Hypothesis: the humoral immune response to oral bacteria provides a stimulus for the development of rheumatoid arthritis. Inflammation. 2004;28(6):311-8.[2]Kharlamova N, Jiang X, Sherina N, Potempa B, Israelsson L, Quirke AM, et al. Antibodies to Porphyromonas gingivalis Indicate Interaction Between Oral Infection, Smoking, and Risk Genes in Rheumatoid Arthritis Etiology. Arthritis Rheumatol. 2016;68(3):604-13.[3]Johansson L, Sherina N, Kharlamova N, Potempa B, Larsson B, Israelsson L, et al. Concentration of antibodies against Porphyromonas gingivalis is increased before the onset of symptoms of rheumatoid arthritis. Arthritis Res Ther. 2016;18(1):201.[4]Rydén L, Buhlin K, Ekstrand E, Faire Ud, Gustafsson A, Holmer J, et al. Periodontitis Increases the Risk of a First Myocardial Infarction. Circulation. 2016;133(6):576-83.Disclosure of Interests:None declared

scholarly journals Novel gene variants associated with cardiovascular disease in systemic lupus erythematosus and rheumatoid arthritis

2018 ◽  
Vol 77 (7) ◽  
pp. 1063-1069 ◽  
Author(s):  
Dag Leonard ◽  
Elisabet Svenungsson ◽  
Johanna Dahlqvist ◽  
Andrei Alexsson ◽  
Lisbeth Ärlestig ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Disease ◽  
General Population ◽  
Lupus Erythematosus ◽  
Risk Allele ◽  
Snp Array ◽  
Inflammatory Rheumatic Diseases ◽  
Systemic Lupus ◽  
Increased Risk

ObjectivesPatients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) have increased risk of cardiovascular disease (CVD). We investigated whether single nucleotide polymorphisms (SNPs) at autoimmunity risk loci were associated with CVD in SLE and RA.MethodsPatients with SLE (n=1045) were genotyped using the 200K Immunochip SNP array (Illumina). The allele frequency was compared between patients with and without different manifestations of CVD. Results were replicated in a second SLE cohort (n=1043) and in an RA cohort (n=824). We analysed publicly available genetic data from general population, performed electrophoretic mobility shift assays and measured cytokine levels and occurrence of antiphospholipid antibodies (aPLs).ResultsWe identified two new putative risk loci associated with increased risk for CVD in two SLE populations, which remained after adjustment for traditional CVD risk factors. An IL19 risk allele, rs17581834(T) was associated with stroke/myocardial infarction (MI) in SLE (OR 2.3 (1.5 to 3.4), P=8.5×10−5) and RA (OR 2.8 (1.4 to 5.6), P=3.8×10−3), meta-analysis (OR 2.5 (2.0 to 2.9), P=3.5×10−7), but not in population controls. The IL19 risk allele affected protein binding, and SLE patients with the risk allele had increased levels of plasma-IL10 (P=0.004) and aPL (P=0.01). An SRP54-AS1 risk allele, rs799454(G) was associated with stroke/transient ischaemic attack in SLE (OR 1.7 (1.3 to 2.2), P=2.5×10−5) but not in RA. The SRP54-AS1 risk allele is an expression quantitative trait locus for four genes.ConclusionsThe IL19 risk allele was associated with stroke/MI in SLE and RA, but not in the general population, indicating that shared immune pathways may be involved in the CVD pathogenesis in inflammatory rheumatic diseases.

scholarly journals The HR2 Haplotype of Factor V Is not Associated with the Risk of Myocardial Infarction

2000 ◽  
Vol 84 (11) ◽  
pp. 815-818 ◽  
Author(s):  
Carine Doggen ◽  
Marieke de Visser ◽  
Hans Vos ◽  
Rogier Bertina ◽  
Volkert Cats ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Factor V Leiden ◽  
Myocardial Infarctions ◽  
Control Group ◽  
Factor V ◽  
Increased Risk ◽  
Factor V Gene ◽  
Heterozygous Carriers ◽  
First Myocardial Infarction ◽  
Control Study

SummaryThe HR2 haplotype of the factor V gene, which contains the histidine to arginine substitution at position 1299, has been reported to be associated with reduced factor V levels. Because high factor V levels have been found to be associated with an increased risk of myocardial infarction, we examined how the presence of the R2 allele affected the risk of myocardial infarction in the case-control “Study of Myocardial Infarctions Leiden”.Among 560 men with a first myocardial infarction before the age of 70 years, 9.5% were heterozygous carriers of the R2 allele. The control group consisted of 646 men, in which 9.9% were heterozygous and 0.2% homozygous carriers of the R2 allele. The risk of myocardial infarction in the presence of the R2 allele was not increased (odds ratio, 0.9; 95% confidence interval 0.6 to 1.4). Exclusion of factor V Leiden carriers did not change this result. The risk was 4.4-fold increased for smokers who carried the R2 allele compared to non-smoking noncarriers. No synergy was found between metabolic risk factors and the presence of the R2 allele.We conclude that the risk of myocardial infarction for men in the presence of the R2 allele of the His1299Arg polymorphism is neither increased nor decreased.

scholarly journals Intracellular Porphyromonas gingivalis Promotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2331 ◽  
Author(s):  
JebaMercy Gnanasekaran ◽  
Adi Binder Gallimidi ◽  
Elias Saba ◽  
Karthikeyan Pandi ◽  
Luba Eli Berchoer ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Porphyromonas Gingivalis ◽  
Xenograft Model ◽  
Oral Bacteria ◽  
Oral Microbiome ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells ◽  
Increased Risk

Porphyromonas gingivalis is a member of the dysbiotic oral microbiome associated with oral inflammation and periodontal disease. Intriguingly, epidemiological studies link P. gingivalis to an increased risk of pancreatic cancer. Given that oral bacteria are detected in human pancreatic cancer, and both mouse and human pancreata harbor microbiota, we explored the involvement of P. gingivalis in pancreatic tumorigenesis using cell lines and a xenograft model. Live P. gingivalis induced proliferation of pancreatic cancer cells; however, surprisingly, this effect was independent of Toll-like receptor 2, the innate immune receptor that is engaged in response to P. gingivalis on other cancer and immune cells, and is required for P. gingivalis to induce alveolar bone resorption. Instead, we found that P. gingivalis survives inside pancreatic cancer cells, a trait that can be enhanced in vitro and is increased by hypoxia, a central characteristic of pancreatic cancer. Increased tumor cell proliferation was related to the degree of intracellular persistence, and infection of tumor cells with P. gingivalis led to enhanced growth in vivo. To the best of our knowledge, this study is the first to demonstrate the direct effect of exposure to P. gingivalis on the tumorigenic behavior of pancreatic cancer cell lines. Our findings shed light on potential mechanisms underlying the pancreatic cancer–periodontitis link.

scholarly journals O2D.1 A follow-up study of occupational styrene exposure and risk of systemic sclerosis, rheumatoid arthritis, and other systemic autoimmune rheumatological diseases

2019 ◽  
Vol 76 (Suppl 1) ◽  
pp. A18.1-A18
Author(s):  
Signe Hjuler Boudigaard ◽  
Zara Ann Stokholm ◽  
Jesper Medom Vestergaard ◽  
Mette Skovgaard Mohr ◽  
Klaus Søndergaard ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Sclerosis ◽  
Lupus Erythematosus ◽  
Systemic Vasculitis ◽  
Time Windows ◽  
Systemic Lupus ◽  
Exposure Response ◽  
Increased Risk ◽  
Primary Systemic Vasculitis ◽  
Styrene Exposure

BackgroundIncreased risk of systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, primary systemic vasculitis, and systemic Sjogren’s syndrome has been suggested following occupational solvent exposure. The evidence for specific solvents is, however, limited and little is known about exposure and risk patterns.AimOur aim is to examine the exposure response relation for systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, primary systemic vasculitis, and systemic Sjogren’s syndrome following occupational styrene exposure.MethodsWe followed 72 467 styrene exposed workers of the Danish reinforced plastics industry from 1977–2012. We modelled styrene exposure from employment history, survey data and historical styrene exposure measurements. We identified cases in a national patient register, and investigated gender specific exposure response relations by cumulative styrene exposure for different exposure time windows adjusting for age, decade, educational level and a proxy for tobacco smoking.ResultsDuring 1,553,577 person-years, we identified 223 women and 453 men diagnosed with a systemic autoimmune rheumatological disease, of which three out of four were rheumatoid arthritis. When adjusting for potential confounders and comparing the highest with the lowest styrene exposure tertile, we observed a statistically non- significantly increased risk of systemic sclerosis among men (IRR=1.79; 95% CI 0.48–6.87) and women (IRR=2.58; 95% CI 0.51–12.94), based on 20 and 9 cases respectively. However, for women with systemic sclerosis, we saw a significantly increasing trend of 1.19 (1.01–1.40) pr. 100 mg/m3-years. Increased risks were also suggested for primary systemic vasculitis (IRR=2.32; 95% CI 0.63–8.52) and rheumatoid arthritis (IRR=1.26; 95% CI 0.95–1.67) among men. Analyses of exposure time windows suggest a latency period for rheumatoid arthritis of about 15 years.ConclusionThis study might indicate that styrene exposure is associated with the occurrence of systemic sclerosis among men and women, and primary systemic vasculitis and rheumatoid arthritis among men.

scholarly journals AB0002 ASSOCIATION OF C1Q GENETIC POLYMORPHISMS WITH SUSCEPTIBILITY TO RHEUMATOID ARTHRITIS IN BULGARIAN COHORT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1036.3-1036
Author(s):  
M. Kosturkova ◽  
G. Mihaylova ◽  
M. Radanova
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Gene Cluster ◽  
Lupus Erythematosus ◽  
Annual Review ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Allelic Discrimination Assay ◽  
Increased Risk

Background:Complement is strongly implicated in the pathogenesis of autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Its component C1q plays a dualistic role, triggering the inflammatory cascade on one hand and directing the clearance of immune complexes on the other. Homozygous genetic deficiency of C1q is strongly associated with SLE and SLE-like phenotype as almost 90% of C1q deficient individuals develop SLE or similar disease. Nevertheless, there are few and inconsistent studies exploring the single nucleotide polymorphisms (SNPs) of the C1q gene cluster in relation to the pathogenesis of SLE and RA.Objectives:The aim of the study was to evaluate the possible association of five SNPs – rs292001, rs172378, rs294179, rs665691 and rs682658 in complement C1q gene cluster with susceptibility to SLE and RA in Bulgarian cohort.Methods:Fifty patients with SLE, sixty-one patients with RA and sixty-seven healthy controls were genotyped for the five SNPs by TaqMan allelic discrimination assay.Results:Frequency of genotypes and alleles of rs294179, rs665691 and rs682658 SNPs was similar between patients with SLE, RA and healthy controls. For rs172378 SNP, the minor G allele (OR = 2.73; 95% CI, 1.59-4.67, p=0.0003) and GG genotype (OR = 5.12; 95% CI, 1.60-16.49, p=0.006) were associated with susceptibility to RA. In our cohort in accordance with others, AA rs292001 SNP genotype was associated with increased risk for RA (OR = 3.32; 95% CI, 1.19-9.20, p=0.021). For SLE patients, AA rs292001 SNP genotype was low presented and did not associate with disease.Conclusion:GG genotype of rs172378 SNP in C1q gene cluster could be considered as a new risk factor for RA.References:[1]Diane Scott et al (2016). The paradoxical roles of C1q and C3 in autoimmunity. Immunobiology, 719-25. doi:10.1016/j.imbio.2015.05.001.[2]Giles JL et al (2015). Functional analysis of a complement polymorphism (rs17611) associated with rheumatoid arthritis. J Immunol., 3029-34. doi:10.4049/jimmunol.1402956.[3]Holers, V. M. (2018). Complement in the Initiation and Evolution of Rheumatoid Arthritis. Frontiers in immunology, 1057. doi:10.3389/fimmu.2018.01057.[4]Lintner, K. E. (2016). Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases. Frontiers in immunology, 36. doi:10.3389/fimmu.2016.00036.[5]Lu, J. &. (2017). C1 Complex: An Adaptable Proteolytic Module for Complement and Non-Complement Functions. Frontiers in immunology, 592. doi:10.3389/fimmu.2017.00592.[6]Manderson, A. P. (2004). The role of complement in the development of systemic lupus erythematosus. Annual review of immunology, 431-456. doi:10.1146/annurev.immunol.22.012703.104549.[7]Martens, H. A. (2009). Analysis of C1q polymorphisms suggests association with systemic lupus erythematosus, serum C1q and CH50 levels and disease severity. Annals of the rheumatic diseases, 715–720. doi:10.1136/ard.2007.085688.[8]Namjou B, G.-M. C. (2009). Evaluation of C1q genomic region in minority racial groups of lupus. Genes Immun., 517-24. doi:10.1038/gene.2009.33.[9]Radanova M et al(2015). Association of rs172378 C1q gene cluster polymorphism with lupus nephritis in Bulgarian patients. Lupus, 280-9. doi:10.1177/0961203314555173.[10]Rafiq S et al (2010). Assessing association of common variation in the C1Q gene cluster with systemic lupus erythematosus. Clin Exp Immunol., 284-9. doi:10.1111/j.1365-2249.2010.04185.x.[11]Schejbel L et al (2011). Molecular basis of hereditary C1q deficiency-revisited: identification of several novel disease-causing mutations. Genes Immun., 626-634.[12]Trouw LA et al (2013). Genetic variants in the region of the C1q genes are associated with rheumatoid arthritis. Clin Exp Immunol., 76-83. doi:10.1111/cei.12097.[13]Trouw L. A. (2017). The complement system as a potential therapeutic target in rheumatic disease. Nature reviews. Rheumatology, 538–547. doi:10.1038/nrrheum.2017.125.[14]Walport M. J. (2002). Complement and systemic lupus erythematosus. Arthritis research, S279–S293. doi:10.1186/ar586.Disclosure of Interests:None declared

scholarly journals Polypharmacy and Unplanned Hospitalizations in Patients with Rheumatoid Arthritis

2017 ◽  
Vol 44 (12) ◽  
pp. 1786-1793 ◽  
Author(s):  
Maria Filkova ◽  
João Carvalho ◽  
Sam Norton ◽  
David Scott ◽  
Tim Mant ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Proportional Hazards ◽  
Hospital Admissions ◽  
Epidemiologic Studies ◽  
Cox Proportional Hazards ◽  
Adjusted Risk ◽  
Increased Risk ◽  
Comorbidity Burden ◽  
Multiple Drugs ◽  
Unplanned Hospital Admissions

Objective.Polypharmacy (PP), the prescribing of multiple drugs for an individual, is rising in prevalence. PP associates with an increased risk of adverse drug reactions (ADR) and hospital admissions. We investigated the relationship between PP, characteristics of rheumatoid arthritis (RA), and the risk of unplanned hospital admissions.Methods.Patients from a hospital RA cohort were retrospectively analyzed. Information was collected from electronic medical records. Cox proportional hazards were used to compare hospitalization risk according to levels of PP. Admissions were adjudicated to determine whether an ADR was implicated.Results.The study included 1101 patients; the mean number of all medications was 5. PP correlated with increasing age, disease duration, disease activity, and disability. At least 1 unplanned admission occurred for 16% of patients. Patients taking ≥ 10 medications had an adjusted HR for hospitalization of 3.1 (95% CI 2.1–4.5), compared to those taking 0–5 medications. Corticosteroid use associated with a doubling in adjusted risk of admission of 1.7 (95% CI 1.2–2.4). The most common reason for hospitalization was infection (28%). While in half of all admissions an ADR was a possible contributing factor, only 2% of admissions were found to directly result from an ADR.Conclusion.PP is common in RA and is a prognostic marker associated with increased risk of acute hospitalizations. Our data suggest that PP may be an indicator of comorbidity burden rather than a contributing cause of a drug-related toxicity. PP should be monitored to minimize inappropriate combination of prescribed medications. PP may be a useful predictor of clinical outcomes in epidemiologic studies.

Interaction Between Smoking and Polymorphism in the Promoter Region of the VEGFA Gene Is Associated with Ischemic Heart Disease and Myocardial Infarction in Rheumatoid Arthritis

2011 ◽  
Vol 38 (5) ◽  
pp. 802-809 ◽  
Author(s):  
YING CHEN ◽  
PETER T. DAWES ◽  
JONATHAN C. PACKHAM ◽  
DEREK L. MATTEY
Keyword(s):  
Rheumatoid Arthritis ◽  
Myocardial Infarction ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Promoter Region ◽  
Ischemic Heart ◽  
Smoking History ◽  
Strong Linkage Disequilibrium ◽  
Increased Risk ◽  
Vegfa Gene

Objective.To determine whether variants in the vascular endothelial growth factor A (VEGFA) gene are associated with ischemic heart disease (IHD) and/or myocardial infarction (MI) in patients with rheumatoid arthritis (RA), and whether there is evidence of a gene-smoking interaction.Methods.PCR-RFLP assays were used to determine the genotypes of VEGFA single-nucleotide polymorphisms (SNP) including VEGFA–2578A/C (rs699947), −460C/T (rs833061), +405C/G (rs2010963), and +936C/T (rs3025039) in 418 subjects with RA. Smoking history was obtained on each patient, and IHD and MI status was recorded. Associations with IHD/MI were assessed using contingency tables and logistic regression analyses.Results.Strong linkage disequilibrium was detected among VEGFA–2578, −460, and +405. SNP located in the VEGFA promoter region (−2578, −460) were found to be associated with IHD and MI, whereas +405 and +936, in the 5′-untranslated region (UTR) and 3′-UTR, respectively, were not. Haplotype analysis suggested that the A/C/G haplotype was associated with increased risk of IHD (OR 2.37, 95% CI 1.22–4.62) and MI (OR 4.10, 95% CI 1.45–11.49). Smoking was also independently associated with IHD and MI, and evidence of interaction between smoking and the VEGFA promoter SNP was found. Multivariate analyses indicated that the strongest associations with IHD and MI were due to the combined effect of the VEGFA–2578 A allele and smoking (OR 3.52 and 7.11, respectively), independent of risk factors such as age, sex, diabetes, C-reactive protein, hypercholesterolemia, and hypertension.Conclusion.Interaction between smoking and polymorphism in the VEGFA gene is associated with IHD and MI in patients with RA.

scholarly journals The problem of accelerated atherosclerosis in systemic lupus erythematosus: Insights into a complex co-morbidity

2011 ◽  
Vol 106 (11) ◽  
pp. 849-857 ◽  
Author(s):  
Nekeithia Wade ◽  
Amy Major
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Disease ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Inflammatory Responses ◽  
Systemic Lupus ◽  
Accelerated Atherosclerosis ◽  
Increased Risk ◽  
Co Morbidity

SummaryRheumatic autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus (SLE), are associated with antibodies to “self” antigens. Persons with autoimmune diseases, most notably SLE, are at increased risk for developing accelerated cardiovascular disease. The link between immune and inflammatory responses in the pathogenesis of cardiovascular disease has been firmly established; yet, despite our increasing knowledge, accelerated atherosclerosis continues to be a significant co-morbidity and cause of mortality in SLE. Recent animal models have been generated in order to identify mechanism(s) behind SLE-accelerated atherosclerosis. In addition, clinical studies have been designed to examine potential treatments options. This review will highlight data from recent studies of immunity in SLE and atherosclerosis and discuss the potential implications of these investigations.

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