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| Name | Class |
|---|---|
| Copenhagen University Hospital, Denmark | OTHER |
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This study evaluates the interaction between host immune cells and bacteria associated with periodontitis. It comprises biological material from donors with and without periodontal disease. Specifically, we collect a spit and blood sample to conduct in vitro stimulations and measurements of selected parameters related to periodontitis to clarify obscure areas in the immunologic pathogenesis of this disease.
Periodontitis is a prevalent, multifactorial inflammatory disease characterized by the interaction between microorganisms organized in biofilms on tooth surfaces and host immune cells, leading to an inflammatory destruction of the tooth-supporting tissues and - if left untreated - eventually tooth loss. Periodontitis affects up to 50% of the population in the United States of America, and is classified in an aggressive and a chronic form depending on genetic factors, age of onset, speed and severity of attachment loss.
The onset of periodontitis is caused by an immunologic imbalance between host immune cells and residing microorganisms in subgingival pockets. The host immune cells are capable of enhancing both a protective and a destructive inflammatory response towards the microorganisms through the release of inflammatory mediators e.i. proinflammatory and antiinflammatory cytokines.
The role of antibodies in periodontitis is also unclear. Some studies show an excessive antibody level against bacteria associated with periodontitis e.g. Porphyromonas gingivalis (P.g.).
In general, this study contributes to a profound understanding of the host immune cells role in the onset and pathogenesis of periodontitis by comparing healthy versus diseased donors immunologic responses toward pathogene and apathogene microorganisms and their genetic background.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chronic periodontitis donors |
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| Aggressive periodontitis donors |
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| Control donors |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| In vitro stimulation of blood with periodontitis-associated- and control bacteria | Other | Peripheral mononuclear blood cells are stimulated with periodontitis-associated- and control bacteria to measure the amount of positive cytokine-producing cells. |
| Measure | Description | Time Frame |
|---|---|---|
| periodontitis-associated- and control bacterial stimulation of host immune cells. | Identification and determination of the amount of cytokine-producing immune cells when stimulated with bacteria associated with periodontitis including pro- and antiinflammatory cytokines. Genuses: Porphyromonas, Prevotella, Eikenella, Aggregatibacter, Actinomyces, Lactobacillus, Bifidobacterium, Rothia. | Aug. 2020 |
| Anti-cyclic citrullinated peptides (anti-CCP) antibodies titers. | Determination of the prevalence of anti-CCP-positive periodontitis patients through measure of anti-CCP antibody titers in serum samples and correlation with the level of antibodies to P. gingivalis, and to the abundancy of the bacterium in saliva. | Aug. 2020 |
| P. gingivalis presence and related antibodies. | Determination of P. gingivalis presence in saliva and serum samples through RT-qPCR and determination of the level of antibodies towards the bacterium using in-house Luminex-based technology. | Aug. 2020 |
| Single nucleotide polymorphism (SNP) analysis. | Investigation of the potential association between periodontitis and selected polymorphisms in the PADI genes using multiplex bead-based SNP assays with the Luminex technology. | Aug. 2020 |
| Measure | Description | Time Frame |
|---|---|---|
| Cytokine profile in saliva. | Determination of the cytokine profile in saliva samples from subject with periodontitis and healthy controls with Luminex based technology. | Aug. 2020 |
| Presence of other periodontal bacteria. |
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Inclusion criteria for chronic periodontitis donors:
Inclusion criteria for aggressive periodontitis donors:
Inclusion criteria for healthy donors: (age: 19-40 years; 50-60 years)
Exclusion criteria for all groups:
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This study includes 170 participants, which are legally competent e.i. above 18 years of age and general decision competent. The participants are divided into three groups: 1) Participants with chronic periodontitis (n=35), 2) participants with aggressive periodontitis (n=35) and 3) healthy participants without periodontal disease (n=100). The participants are recruited from the Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark and assigned to a group in accordance with the periodontal disease classification system in 1999 American Academy of Periodontology.
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| Name | Affiliation | Role |
|---|---|---|
| Palle Holmstrup, DDS, PhD, Dr Odont | University of Copenhagen | Study Director |
| Claus Henrik Nielsen, PhD, MSc, MD | Rigshospitalet, Denmark | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital. | Copenhagen | 2200 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23574467 | Background | Bartold PM, Van Dyke TE. Periodontitis: a host-mediated disruption of microbial homeostasis. Unlearning learned concepts. Periodontol 2000. 2013 Jun;62(1):203-17. doi: 10.1111/j.1600-0757.2012.00450.x. | |
| 11525431 | Background | Neely AL, Holford TR, Loe H, Anerud A, Boysen H. The natural history of periodontal disease in man. Risk factors for progression of attachment loss in individuals receiving no oral health care. J Periodontol. 2001 Aug;72(8):1006-15. doi: 10.1902/jop.2001.72.8.1006. |
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IPD will not be available to other researchers in accordance with our approved Human Subjects Protection application in Denmark.
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Saliva, whole blood, peripheral mononuclear blood cells, serum, plasma.
| Anti-CCP- and anti-P.g.-antibodies titers | Diagnostic Test | Anitbody titers will be measured in saliva and serum samples. |
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| Analysis of selected single nucleotide polymorphisms (SNPs) | Genetic | DNA obtained from saliva samples will be used to determine the genotype of the participants for selected SNPs. |
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| periodontitis-associated bacteria presence | Diagnostic Test | Determination of the presence of periodontitis-associated bacteria e.i. Porphyromonas gingivalis in saliva and blood samples. |
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Determination of the presence of other periodontal bacteria through RT-qPCR assays.
| Aug. 2020 |
| Section for Periodontology, Microbiology and Community Dentistry, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen | Copenhagen | 2200 | Denmark |
| 25688694 | Background | Eke PI, Dye BA, Wei L, Slade GD, Thornton-Evans GO, Borgnakke WS, Taylor GW, Page RC, Beck JD, Genco RJ. Update on Prevalence of Periodontitis in Adults in the United States: NHANES 2009 to 2012. J Periodontol. 2015 May;86(5):611-22. doi: 10.1902/jop.2015.140520. Epub 2015 Feb 17. |
| 11413609 | Background | Armitage GC. Development of a classification system for periodontal diseases and conditions. Northwest Dent. 2000 Nov-Dec;79(6):31-5. |
| 18402605 | Background | Haffajee AD, Socransky SS, Patel MR, Song X. Microbial complexes in supragingival plaque. Oral Microbiol Immunol. 2008 Jun;23(3):196-205. doi: 10.1111/j.1399-302X.2007.00411.x. |
| 25040158 | Background | Damgaard C, Holmstrup P, Van Dyke TE, Nielsen CH. The complement system and its role in the pathogenesis of periodontitis: current concepts. J Periodontal Res. 2015 Jun;50(3):283-93. doi: 10.1111/jre.12209. Epub 2014 Jul 5. |
| 20017801 | Background | Liu YC, Lerner UH, Teng YT. Cytokine responses against periodontal infection: protective and destructive roles. Periodontol 2000. 2010 Feb;52(1):163-206. doi: 10.1111/j.1600-0757.2009.00321.x. No abstract available. |
| 21323703 | Background | Kinane DF, Preshaw PM, Loos BG; Working Group 2 of Seventh European Workshop on Periodontology. Host-response: understanding the cellular and molecular mechanisms of host-microbial interactions--consensus of the Seventh European Workshop on Periodontology. J Clin Periodontol. 2011 Mar;38 Suppl 11:44-8. doi: 10.1111/j.1600-051X.2010.01682.x. |
| 12714435 | Background | Pussinen PJ, Jousilahti P, Alfthan G, Palosuo T, Asikainen S, Salomaa V. Antibodies to periodontal pathogens are associated with coronary heart disease. Arterioscler Thromb Vasc Biol. 2003 Jul 1;23(7):1250-4. doi: 10.1161/01.ATV.0000072969.71452.87. Epub 2003 Apr 24. |
| 15692101 | Background | Pussinen PJ, Nyyssonen K, Alfthan G, Salonen R, Laukkanen JA, Salonen JT. Serum antibody levels to Actinobacillus actinomycetemcomitans predict the risk for coronary heart disease. Arterioscler Thromb Vasc Biol. 2005 Apr;25(4):833-8. doi: 10.1161/01.ATV.0000157982.69663.59. Epub 2005 Feb 3. |
| 16128832 | Background | Berglundh T, Donati M. Aspects of adaptive host response in periodontitis. J Clin Periodontol. 2005;32 Suppl 6:87-107. doi: 10.1111/j.1600-051X.2005.00820.x. |
| 23253921 | Background | Fillatreau S. Cytokine-producing B cells as regulators of pathogenic and protective immune responses. Ann Rheum Dis. 2013 Apr;72 Suppl 2:ii80-4. doi: 10.1136/annrheumdis-2012-202253. Epub 2012 Dec 19. |
| 26782357 | Background | Belstrom D, Paster BJ, Fiehn NE, Bardow A, Holmstrup P. Salivary bacterial fingerprints of established oral disease revealed by the Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS) technique. J Oral Microbiol. 2016 Jan 14;8:30170. doi: 10.3402/jom.v8.30170. eCollection 2016. |
| 26987356 | Background | Belstrom D, Holmstrup P, Bardow A, Kokaras A, Fiehn NE, Paster BJ. Comparative analysis of bacterial profiles in unstimulated and stimulated saliva samples. J Oral Microbiol. 2016 Mar 16;8:30112. doi: 10.3402/jom.v8.30112. eCollection 2016. |
| 36715211 | Derived | Danielsen AK, Damgaard C, Massarenti L, Ostrup P, Riis Hansen P, Holmstrup P, Nielsen CH. B-cell cytokine responses to Porphyromonas gingivalis in patients with periodontitis and healthy controls. J Periodontol. 2023 Aug;94(8):997-1007. doi: 10.1002/JPER.22-0438. Epub 2023 Mar 5. |
| ID | Term |
|---|---|
| D010510 | Periodontal Diseases |
| D010518 | Periodontitis |
| D010520 | Aggressive Periodontitis |
| D007154 | Immune System Diseases |
| D010514 | Periodontal Pocket |
| D007249 | Inflammation |
| D005891 | Gingivitis |
| D064806 | Dysbiosis |
| D001172 | Arthritis, Rheumatoid |
| D055113 | Chronic Periodontitis |
| ID | Term |
|---|---|
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007239 | Infections |
| D005882 | Gingival Diseases |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
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