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- De Vries, C, et al.
(författare)
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ANTIBODIES TO PORPHYROMONAS GINGIVALIS ASSOCIATE WITH THE PRESENCE OF RHEUMATOID ARTHRITIS-RELATED AUTOANTIBODIES IN PATIENTS WITH PERIODONTITIS
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 996-996
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- 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
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- Gustafsson, Nils, et al.
(författare)
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Associations among Periodontitis, Calcified Carotid Artery Atheromas, and Risk of Myocardial Infarction
- 2020
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Ingår i: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 99:1, s. 60-68
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular disease is a common cause of morbidity and premature mortality. Cardiovascular disease can be prevented when risk factors are identified early. Calcified carotid artery atheromas (CCAAs), detected in panoramic radiographs, and periodontitis have both been associated with increased risk of cardiovascular disease. This case-control study aimed to 1) investigate associations between periodontitis and CCAA detected in panoramic radiographs and 2) determine the risk of future myocardial infarctions due to CCAA combined with periodontitis. We evaluated 1,482 participants (738 cases and 744 controls) with periodontitis and CCAAs recruited from the PAROKRANK study (Periodontitis and Its Relation to Coronary Artery Disease). Participants were examined with panoramic radiographs, including the carotid regions. Associations between myocardial infarction and periodontitis combined with CCAA were evaluated in 696 cases and 696 age-, sex-, and residential area-matched controls. Periodontitis was evaluated radiographically (as degree of bone loss) and with a clinical periodontal disease index score (from clinical and radiographic assessments). We found associations between CCAA and clinical periodontal disease index score among cases (odds ratio [OR], 1.51; 95% CI, 1.09 to 2.10; P = 0.02) and controls (OR, 1.70; 95% CI, 1.22 to 2.38; P < 0.01), although not between CCAA and the degree of bone loss. In a multivariable model, myocardial infarction was associated with CCAA combined with periodontitis, as assessed by degree of bone loss (OR, 1.75; 95% CI, 1.11 to 2.74; P = 0.01). When the cohort was stratified by sex, only men showed a significant association between myocardial infarction and CCAA combined with periodontitis. Participants with clinically diagnosed periodontitis exhibited CCAA in panoramic radiographs more often than those without periodontitis, irrespective of the presence of a recent myocardial infarction. Participants with combined periodontitis and CCAA had a higher risk of having had myocardial infarction as compared with participants with either condition alone. These findings implied that patients in dental care might benefit from dentists assessing panoramic radiographs for CCAA-particularly, patients with periodontitis who have not received any preventive measures for cardiovascular disease.
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- Nass, K., et al.
(författare)
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In cellulo crystallization of Trypanosoma brucei IMP dehydrogenase enables the identification of genuine co-factors
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Sleeping sickness is a fatal disease caused by the protozoan parasite Trypanosoma brucei (Tb). Inosine-5'-monophosphate dehydrogenase (IMPDH) has been proposed as a potential drug target, since it maintains the balance between guanylate deoxynucleotide and ribonucleotide levels that is pivotal for the parasite. Here we report the structure of TbIMPDH at room temperature utilizing free-electron laser radiation on crystals grown in living insect cells. The 2.80 angstrom resolution structure reveals the presence of ATP and GMP at the canonical sites of the Bateman domains, the latter in a so far unknown coordination mode. Consistent with previously reported IMPDH complexes harboring guanosine nucleotides at the second canonical site, TbIMPDH forms a compact oligomer structure, supporting a nucleotide-controlled conformational switch that allosterically modulates the catalytic activity. The oligomeric TbIMPDH structure we present here reveals the potential of in cellulo crystallization to identify genuine allosteric co-factors from a natural reservoir of specific compounds. Trypanosoma brucei inosine-5 '-monophosphate dehydrogenase (IMPDH) is an enzyme in the guanine nucleotide biosynthesis pathway and of interest as a drug target. Here the authors present the 2.8 angstrom room temperature structure of TbIMPDH determined by utilizing X-ray free-electron laser radiation and crystals that were grown in insect cells and find that ATP and GMP are bound at the canonical sites of the Bateman domains.
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- Sayols-Baixeras, Sergi, et al.
(författare)
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Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort
- 2023
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 148:6, s. 459-472
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates.Methods: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of stool, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.Results: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10-5). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.Conclusions: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
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- Sayols-Baixeras, Sergi, et al.
(författare)
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Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort
- 2023
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Ingår i: Circulation. - : American Heart Association. - 0009-7322 .- 1524-4539. ; 148:6, s. 459-472
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography–based measures of coronary atherosclerosis and to explore relevant clinical correlates.METHODS: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal samples, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.RESULTS: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10–5). Associations were largely similar across coronary computed tomography angiography–based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.CONCLUSIONS: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
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