Interaction Between Immune Cells and Bacteria Associated With Periodontitis

NCT03225950 | Completed

• 1 other identifier: H-16024734
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Periodontal Diseases; Periodontitis; Aggressive Periodontitis; Immunologic Disease; Microbial Disease; Periodontal Pocket; Inflammation; Inflammation Gum; Dysbiosis; Rheumatoid Arthritis; Generalized Aggressive Periodontitis; Generalized Chronic Periodontitis; Chronic Periodontitis

Keywords

Periodontal disease; Periodontitis; Aggressive periodontitis; Dysbiosis; Inflammation; Regulation; Cytokines; Bacteria; Porphyromonas gingivalis; Saliva; Anti-CCP; Peptidyl arginine deiminases; Single nucleotide polymorphisms

Outcome Measures

Primary Outcomes (4)

• 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

Secondary Outcomes (2)

• Cytokine profile in saliva.

  Aug. 2020

• Presence of other periodontal bacteria.

  Aug. 2020

Study Arms (3)

Chronic periodontitis donors

* Donors are medically healthy. * Slow to moderate attachment loss and bone destruction. * Good correlation between etiological factors and serverity of attachment loss.

Other: In vitro stimulation of blood with periodontitis-associated- and control bacteria; Diagnostic Test: Anti-CCP- and anti-P.g.-antibodies titers; Genetic: Analysis of selected single nucleotide polymorphisms (SNPs); Diagnostic Test: periodontitis-associated bacteria presence

Aggressive periodontitis donors

* Donors are medically healthy. * Rapid attachment loss and bone destruction. * Familial aggregation. * No correlation between etiological factors and serverity of attachment loss.

Other: In vitro stimulation of blood with periodontitis-associated- and control bacteria; Diagnostic Test: Anti-CCP- and anti-P.g.-antibodies titers; Genetic: Analysis of selected single nucleotide polymorphisms (SNPs); Diagnostic Test: periodontitis-associated bacteria presence

Control donors

* Donors are medically healthy. * No sign of inflammatory conditions.

Other: In vitro stimulation of blood with periodontitis-associated- and control bacteria; Diagnostic Test: Anti-CCP- and anti-P.g.-antibodies titers; Genetic: Analysis of selected single nucleotide polymorphisms (SNPs); Diagnostic Test: periodontitis-associated bacteria presence

Interventions

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.

Aggressive periodontitis donors; Chronic periodontitis donors; Control donors

Anti-CCP- and anti-P.g.-antibodies titers DIAGNOSTIC_TEST

Anitbody titers will be measured in saliva and serum samples.

Aggressive periodontitis donors; Chronic periodontitis donors; Control donors

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.

Aggressive periodontitis donors; Chronic periodontitis donors; Control donors

periodontitis-associated bacteria presence DIAGNOSTIC_TEST

Determination of the presence of periodontitis-associated bacteria e.i. Porphyromonas gingivalis in saliva and blood samples.

Aggressive periodontitis donors; Chronic periodontitis donors; Control donors

Eligibility Criteria

• Age: 19 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• years of age.
• Interproximal attachment loss at minimum 3 teeth besides molars and incisors.
• Clinical attachment loss at minimum 10 sites identified by bleeding and pus upon probing.
• Visible radiographic bone loss.
• Medically healthy donors.
• years of age.
• Interproximal attachment loss at minimum 3 teeth besides molars and incisors.
• Clinical attachment loss at minimum 10 sites identified by bleeding and pus upon probing.
• Visible radiographic bone loss.
• Medically healthy donors.
• No sign of inflammatory conditions or other general systemic diseases.
• Medically healthy donors.

You may not qualify if:

• Pregnant and breastfeeding.
• Antibiotic treatment within 6 months.
• Suffer from periodontal manifestations caused by systemic diseases e.i. genetic diseases, haematologic anomalies or syndromes.

Sponsors & Collaborators

• University of Copenhagen: lead
• Copenhagen University Hospital, Denmark: collaborator

Study Sites (2)

Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital.

Copenhagen, 2200, Denmark

Location

Section for Periodontology, Microbiology and Community Dentistry, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen

Copenhagen, 2200, Denmark

Location

Related Publications (15)

• 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.

  PMID: 23574467 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.

  PMID: 11525431 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.

  PMID: 25688694 BACKGROUND

• Armitage GC. Development of a classification system for periodontal diseases and conditions. Northwest Dent. 2000 Nov-Dec;79(6):31-5.

  PMID: 11413609 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.

  PMID: 18402605 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.

  PMID: 25040158 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.

  PMID: 20017801 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.

  PMID: 21323703 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.

  PMID: 12714435 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.

  PMID: 15692101 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.

  PMID: 16128832 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.

  PMID: 23253921 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.

  PMID: 26782357 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.

  PMID: 26987356 BACKGROUND

• 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.

  PMID: 36715211 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Saliva, whole blood, peripheral mononuclear blood cells, serum, plasma.

MeSH Terms

Conditions

Periodontal Diseases; Periodontitis; Aggressive Periodontitis; Immune System Diseases; Periodontal Pocket; Inflammation; Gingivitis; Dysbiosis; Arthritis, Rheumatoid; Chronic Periodontitis

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Gingival Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Chronic Disease; Disease Attributes

Study Officials

• Palle Holmstrup, DDS, PhD, Dr Odont

  University of Copenhagen

  STUDY DIRECTOR

• Claus Henrik Nielsen, PhD, MSc, MD

  Rigshospitalet, Denmark

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Assistant

Study Record Dates

• First Submitted: July 19, 2017
• First Posted: July 21, 2017
• Study Start: February 1, 2017
• Primary Completion: October 12, 2018
• Study Completion: March 23, 2020
• Last Updated: March 24, 2020

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)