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Periodontitis is a major public health problem because it is widespread in the adult population. It leads to the irreversible destruction of the anchoring tissues of the teeth, and represents a modifiable risk factor for systemic inflammatory pathologies. This chronic inflammatory disease, which is associated with oral dysbiosis involving Porphyromonas gingivalis, is triggered by a permissive immune response. It is preceded by a reversible clinical phase, during which there is no bone resorption process: gingivitis. The understanding of the key mechanisms involved in the evolution from gingivitis to periodontitis, which will allow to early identify patient at risk of periodontitis, remain unclear at this time.
Neutrophils are the main cells of inflammation present within the periodontal pockets. The excess of certain neutrophils or the alteration of their functions is associated with the triggering of periodontitis, whereas their activity, finely orchestrated, would be a key to periodontal homeostasis. It is likely that some periodontal bacteria, including P. gingivalis, but also products of matrix catabolism could deregulate the physiological functions of neutrophils towards pro-inflammatory and catabolic profiles. Moreover, to date, the differentiation and role of neutrophil subsets in periodontal homeostasis as well as in gingivitis and its evolution into periodontitis remain poorly studied.
The investigators hypothesize that various subsets of neutrophils may play different roles during the development of periodontitis (evolution of gingivitis to periodontitis).
The primary objective is to characterize neutrophil subtypes associated with periodontal destruction during periodontitis.
Secondary objectives are :
It's a cross-sectional, monocenter prospective, open-label, non randomized case control 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.
Patients will be recruited in the oral medicine departments of AP-HP Charles Foix hospital (Ivry/seine) by periodontists in three groups (Cases : Group 1 : Gingivitis, Group 2 : Periodontitis, and Controls = healthy periodontium. All patients will require surgical care).
The time-line of the research is consistent with the usual patient management in oral medicine departments. Inclusion period is 36 months. There is no specific follow-up due to the research. Gingival tissue sampling during surgery of patients will be performed after their inclusion.
Assessment Criteria :
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Periodontitis Cases | Patients with stage 3 or 4 periodontitis (Chicago 2017) ; BOP ≥ 10%, PD≥ 4mm Patients requiring surgical care such as dental avulsion or pre-prosthetic periodontal surgeries |
| |
| Gingivitis Cases | BOP ≥ 10%, PD≤ 3mm according to Chicago 2017 Patients requiring surgical care such as dental avulsion or pre-prosthetic periodontal surgeries |
| |
| Control | BOP < 10%, PD≤ 3mm Patients with gingival health on intact or reduced periodontium without a history of periodontitis and requiring surgical care such as dental avulsion or aesthetic surgeries |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Biological sampling in Periodontitis Case | Other | Periodontal bacteria, gingival fluid, unstimulated saliva and blood collection; J+7 : tooth extraction : gingival explant sampling J+15 : Healing control |
| Measure | Description | Time Frame |
|---|---|---|
| Description of neutrophil subtypes associated with periodontal destruction in periodontitis based on coexpression of markers of neutrophil function . | Distinction of neutrophil subtypes based on coexpression of markers of neutrophil function from a panel of 24 markers by imaging on tissue sections | 36 months |
| Measure | Description | Time Frame |
|---|---|---|
| Identify specific interactions of activated tissue neutrophils with the matrix microenvironment during periodontitis using Immunohistofluorescence identification of the expression of some matrix proteins. | Immunohistofluorescence identification (on tissue) of the expression of matrix proteins described as regulators of neutrophil function, and search for co-localization between said proteins/peptides and certain subtypes of neutrophils |
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Inclusion Criteria:
Common criteria for all patient groups
Specific Criteria :
Exclusion Criteria:
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This study concerns adult patients consulting the oral medicine department at Hôpital Charles Foix (AP-HP, Ivry sur Seine)
Cases :
The diagnosis of gingivitis or periodontitis is based on the elements noted during the clinical interview and examination, in accordance with the Chicago 2017 classification.
Control:
Patient with healthy gingiva on intact or reduced periodontium with no history of periodontitis, in accordance with the Chicago 2017 classification.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Marjolaine Gosset, PU-PH | Contact | 01 49 59 48 11 | marjolaine.gosset@u-paris.fr | |
| François Ferré, MCU-PH | Contact | 01 49 59 48 11 | françois.ferre@aphp.fr |
| Name | Affiliation | Role |
|---|---|---|
| Marjolaine Gosset, PU-PH | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Charles-Foix Hospital | Recruiting | Ivry-sur-Seine | 94200 | France |
Data are available upon reasonable request The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.
Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
Researchers who provide a methodologically sound proposal
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| ID | Term |
|---|---|
| D010518 | Periodontitis |
| D005891 | Gingivitis |
| ID | Term |
|---|---|
| D010510 | Periodontal Diseases |
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
| D007239 | Infections |
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gingival tissue and fluid, saliva and serum samples
| Biological sampling in Gingivitis Case | Other | Periodontal bacteria, gingival fluid, unstimulated saliva and blood collection; J+7 : tooth extraction or pre-prosthetic periodontal surgeries : gingival explant sampling J+15 : Healing control |
|
| Biological sampling in Control Case | Other | Periodontal bacteria, gingival fluid, unstimulated saliva and blood collection; J+7 : tooth extraction or pre-prosthetic periodontal surgeries : gingival explant sampling J+15 : Healing control |
|
| 36 months |
| Identify interactions of activated tissue or oral neutrophils with the oral microbiota using Immunohistofluorescence identification of key bacteria and investigation of co-localization between bacteria and certain subtypes of neutrophils | Immunohistofluorescence identification (on tissue) of key bacteria in oral dysbiosis during periodontitis and investigation of co-localization between bacteria and certain subtypes of neutrophils | 36 months |
| Describe oral (salivary) neutrophil subtypes during periodontal health, gingivitis and periodontitis based on coexpression of markers of neutrophil function. | Evaluation of neutrophil subtypes present in patient saliva and study of correlation with tissue neutrophils during periodontal health, gingivitis and periodontitis | 36 months |
| Evaluate the differenciation, particularly proosteoclastogenic, of oral neutrophils, in comparison with blood neutrophils, stimulated by infection using morphological criteria like the number of nuclei and cell size | osteoclast differentiation will be analyzed using morphological criteria, like the number of nuclei | 36 months |
| Evaluate the differenciation, particularly proosteoclastogenic, of oral neutrophils, in comparison with blood neutrophils, stimulated by infection using morphological criteria like the cell size | osteoclast differentiation will be analyzed using morphological criteria, like cell size | 36 months |
| Evaluate the activity, particularly proosteoclastogenic, of oral neutrophils, in comparison with blood neutrophils, stimulated by infection, using functional criteria such as resorption activity (size of lacunae formed by the cells on culture dishes) | Osteoclast activity will be assessed by functional criteria such as resorption activity (size of lacunae formed by the cells on specific culture dishes) | 36 months |
| Evaluate the activity, particularly proosteoclastogenic, of oral neutrophils, in comparison with blood neutrophils, stimulated by infection, using functional criteria such as expression of activity markers by Trap staining | Osteoclast activity will be assessed by functional criteria such as expression of activity markers (Trap staining) | 36 months |
| D005882 |
| Gingival Diseases |