Periodontitis and Inflammation

Assistance Publique - Hôpitaux de Paris219 enrolled

Overview

Today, to understand pathogenic mechanisms involved in periodontitis and peri-implantitis remains a challenge to identify biomarkers or therapeutic targets to improve prevention and screening, as well as the effectiveness of periodontitis and peri-implantitis treatments. The aim is to characterize, in vivo, specific molecular markers reflecting the activity of the pathology, which could lead to * improve the knowledge of the pathogenesis of periodontitis and peri-implantitis; * determine target molecules involved in tissue destruction; * determine molecular profiles of patients at local and systemic risk; * determine therapeutic targets For this purpose, biological samples will be collected (plaque, saliva, crevicular fluid) from patients with periodontitis or peri-implantitis stage 3 or 4 versus patients with a healthy periodontium. Biological samples will be collected before and all along the periodontal or peri-implantal treatment. Gingiva explants collection will be sampling within the surgical procedures (if they are needed). The primary objective is to investigate tissue and cellular expression of molecular markers associated with periodontal destruction during periodontitis or peri-implantitis in relation to periodontal infection and systemic changes in host response. A characterization of the cytokines in gingival fluid and unstimulated saliva (Luminex® technique) of patients with periodontitis or peri-implantitis versus without periodontitis or peri-implantitis will be done. The secondary objective is to study the influence of periodontitis on systemic pathologies via serum analysis of molecules and bacteria involved in periodontal destruction. Immunofluorescence evaluation of protein expression and distribution (inflammatory mediators, inflammatory pathway signaling proteins) in gingival explants, characterization of proteases (MMP) present in gingival fluid and unstimulated saliva (Luminex® technique) and microbiological analysis of the subgingival biofilm (by quantitative PCR).

Today, to understand pathogenic mechanisms involved in periodontitis and peri-implantitis remains a challenge to identify biomarkers or therapeutic targets to improve prevention and screening, as well as the effectiveness of periodontitis and peri-implantitis treatments. The aim is to characterize, in vivo, specific molecular markers reflecting the activity of the pathology, which could lead to * improve the knowledge of the pathogenesis of periodontitis and peri-implantitis; * determine target molecules involved in tissue destruction; * determine molecular profiles of patients at local and systemic risk; * determine therapeutic targets The research focuses on the characterization of the immuno-inflammatory response involved in periodontitis and peri-implantitis. A characterization of the mediators or cells involved will be performed from biological samples (gingival fluid, unstimulated saliva, gingival explants). The gingival fluid is composed of serum inflammatory exudate and inflammatory mediators produced locally in the periodontal pocket. Unstimulated saliva is a biological fluid composed in part of the gingival fluid that drains into it. It has the advantage of being easier to collect (larger quantity, collection by any health professional). This is a non-interventional, cross-sectional, multicenter, prospective, open-label, non-randomized study to collect tissue, crevicular, salivary, and serum samples as part of the patient's routine care in oral medicine departments to form a biological collection. The samples and the clinical data of the patients (excel file with anonymized data and locked by a password) will be transferred to UMR1333 for their analysis. Patients will be recruited in the oral medicine departments of AP-HP hospitals (Charles Foix (Ivry/seine) and Rothschild (Paris) by periodontists in three groups (cases = periodontitis or peri-implantitis and controls = healthy periodontium but patients requiring surgical care). The time-line of the research is consistent with the usual patient management in oral medicine departments. Inclusion period is 60 months. There is no specific follow-up due to the research. Gingival tissue sampling during surgery of patients will be performed after their inclusion.

Interventions

Periodontal or peri-implantitis treatmentPROCEDURE

For Cases : * Inclusion; Bacterial sampling, gingival fluid and unstimulated saliva collection; Teaching of oral hygiene techniques. * Non-surgical periodontal or peri-implantal treatment * At 3 months = periodontal or peri-implantal reevaluation; Bacterial sampling, gingival fluid and unstimulated saliva collection * If periodontal or peri-implantal pockets greater than 5mm and bleeding persist: surgery and gingival explant sampling * At 3 months post-surgery = periodontal or peri-implantal re-evaluation; Bacterial sampling, gingival fluid and unstimulated saliva collection * Maintenance

Control treatmentPROCEDURE

For Controls: * Inclusion; Bacterial sampling, gingival fluid and unstimulated saliva collection, teaching of oral hygiene techniques. * Plastic or pre-prosthetic surgery = gingival explant sampling * Healing control at 15 days

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: Common criteria for all patient groups * Patient \> 18 years old * Patient affiliated to a social security system, beneficiary or beneficiary of a right other than AME * Patient who speaks and understands French well enough to be able to read and understand the study information note. * Patient who does not object to his participation in the study Specific criteria: \- Case Periodontitis: Patient with localized or generalized periodontitis, stage 3 or 4. The diagnosis of periodontitis is based on the elements found during the interview and clinical examination \- Case peri-implantitis: Patients with at least 1 implant affected by peri-implantitis. Diagnosis is based on the findings of the interview, clinical examination and radiographic examination. Control group: Patient with gingival health on intact or reduced periodontium with no history of periodontitis or peri-implantitis and requiring surgical care such as dental avulsion and pre-prosthetic periodontal corrective/aesthetic surgeries (coronal elongation, neck alignment.) Exclusion Criteria: * Patients who have received antibiotic prophylaxis, antibiotic therapy, or anti-inflammatory treatment within 3 months prior to inclusion * Pregnant or breastfeeding women * Patient included in another interventional research protocol or in a period of exclusion. * Patients under guardianship, curatorship or legal protection. * Patient having expressed his opposition to participate in the research

Outcomes

Primary Outcomes

Characterization of a panel of cytokines in gingival fluid of patients with periodontitis versus without periodontitis

Analysis of gingival fluids and unstimulated saliva by the Luminex allows detection and quantification of 15 cytokines (IL- 1α, IL- 1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, IL-18, IFN γ, TNF) simultaneously

Time frame: 1 month once the collection is completed

Secondary Outcomes

Cytokines expression in periodontal cells

Analysis of cytokines, inflammation pathways and inflammation cells by histological analysis (immunofluorescence) of surgical specimens.

Time frame: 6 months once the collection is completed

Cytokines expression in periodontal cells

Immunofluorescence evaluation of protein distribution (inflammatory mediators, inflammatory pathway signaling proteins) in gingival explants (confocal microscopy analysis).

Time frame: 6 months once the collection is completed

Microbiological analysis of the subgingival biofilm determination of the percentage of periodontopathogens.

assessment through RT-PCR

Time frame: 3 months once the collection is completed

Characterization of proteases (MMP) present in gingival fluid and unstimulated saliva

assessment through Luminex®