Clinical trial NCT06984237: Evaluation of Salivary and Serum Levels of TNF-α, IL-17A, and YKL-40 in Individuals With Psoriasis
Official title: Psoriasis and Periodontitis Are Chronic Inflammatory Diseases That May Share Common Immunopathogenic Pathways. TNF-α, IL-17A, and YKL-40 Are Inflammatory Biomarkers Associated With Both Conditions. This Study Aims to Evaluate the Levels of These Markers in Saliva and Serum of Individuals With Psoriasis, Considering Their Periodontal Status, to Investigate a Potential Link Between the Two Diseases
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Periodontitis
Psoriasis
Keywords: TNF-α
IL-17A
YKL-40
salivary
serum
Lead sponsor: Akdeniz University
Sponsor class: OTHER
First posted: 2025-05-22
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A total of 100 participants are included after providing informed consent and meeting inclusion criteria. Participants are divided into five equal groups (n=20 per group):

1. Systemically and periodontally healthy individuals (H),
2. Systemically healthy individuals with gingivitis (Control Gingivitis, CG),
3. Systemically healthy individuals with periodontitis (Control Periodontitis, CP),
4. Individuals with psoriasis and gingivitis (Psoriasis Gingivitis, PG), and
5. Individuals with psoriasis and periodontitis (Psoriasis Periodontitis, PP).

Periodontal diagnoses are made based on the 2017 classification system of the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP).

Brief summary: Background: Periodontitis is a chronic inflammatory disease triggered by microbial infections that lead to the destruction of tissues supporting the teeth. Psoriasis is a chronic skin condition characterized by excessive proliferation and abnormal differentiation of keratinocytes. Due to the presence of similar inflammatory mechanisms, an immunological relationship between psoriasis and periodontal disease has been hypothesized. To explore this relationship, the levels of TNF-α, IL-17A, and YKL-40 in saliva and serum will be examined in both systemically healthy individuals and individuals with psoriasis.

Methods: The study will include five distinct groups based on systemic and periodontal conditions:

1. systemically and periodontally healthy individuals (H),
2. systemically healthy individuals with gingivitis (Control Gingivitis, CG),
3. systemically healthy individuals with periodontitis (Control Periodontitis, CP),
4. individuals with psoriasis and gingivitis (Psoriasis Gingivitis, PG), and
5. individuals with psoriasis and periodontitis (Psoriasis Periodontitis, PP). Levels of TNF-α, IL-17A, and YKL-40 will be measured in both saliva and serum samples. Additionally, correlations among these cytokines and between cytokine levels and clinical periodontal parameters-including Plaque Index (PI), Bleeding on Probing (BOP), Probing Pocket Depth (PPD), and Clinical Attachment Level (CAL)-will be analyzed.

Conclusion: The study is expected to provide insight into the immunological link between psoriasis and periodontal disease by evaluating TNF-α, IL-17A, and YKL-40 levels at both local (saliva) and systemic (serum) levels.

Detailed description: Periodontitis is a chronic inflammatory disease affecting the supporting structures of the teeth, characterized by gingival inflammation, destruction of periodontal tissues, and alveolar bone loss. The disease primarily develops due to bacterial colonization at the tooth-gingival interface. Inflammatory mediators released in response to the interaction between a dysbiotic microbial biofilm and the host immune system play a critical role in tissue destruction and disease progression. Systemic conditions that affect the host immune system may exacerbate periodontal destruction in this multifactorial disease.

Psoriasis is a chronic inflammatory skin condition characterized by erythematous plaques or papules covered with silvery-white scales. The prevalence ranges between 1% and 3%, depending on the ethnic population, and it affects both genders equally. Although the exact etiopathogenesis of psoriasis remains unclear, several environmental and systemic factors-such as trauma, ultraviolet radiation, infections, medications, endocrine influences, psychological stress, alcohol consumption, and smoking-have been identified as potential triggers.

A possible association between psoriasis and periodontitis has been reported in multiple clinical studies and meta-analyses. Interleukin-17 (IL-17) is a pro-inflammatory cytokine that induces the expression of various inflammation-related mediators. It plays a central role in immune regulation and is implicated in inflammatory diseases, autoimmune disorders, and cancer. Elevated IL-17A levels have been detected in both psoriatic skin and serum samples of individuals with psoriasis when compared to healthy controls.

Tumor necrosis factor-alpha (TNF-α) is a polypeptide cytokine produced primarily by macrophages and monocytes. It functions as a multipotent regulator in immune responses by stimulating fibroblasts to release collagenase, increasing vascular permeability, promoting the release of other cytokines (such as IL-1α, IL-1β, IL-6, and IL-8), and enhancing the production of matrix metalloproteinases and adhesion molecules. TNF-α also synergizes with IL-1 to promote bone resorption. Elevated TNF-α levels in both serum and psoriatic lesions have been shown to decrease following effective treatment.

YKL-40 is a 40-kDa glycoprotein composed of tyrosine (Y), lysine (K), and leucine (L) at its N-terminal. It is secreted by neutrophils, macrophages, chondrocytes, synovial cells, osteoblasts, endothelial cells, and cancer cells. YKL-40 is associated with immune responses involving inflammation, tissue remodeling, and angiogenesis, and is considered an acute-phase protein.

A limited number of studies addressing the pathogenesis-related association between psoriasis and periodontal status have been identified in the literature, indicating a need for further investigation. To address this gap, a study is planned in which biomarkers associated with both periodontitis and psoriasis will be evaluated at both local and systemic levels.

The primary objective will be to comparatively assess TNF-α, IL-17A, and YKL-40 levels in saliva and serum samples of individuals with psoriasis, along with relevant clinical periodontal parameters.

Eligibility criteria: Inclusion Criteria

* Voluntary participation
* No use of antibiotics within the past 6 months
* No periodontal treatment within the past 6 months
* Absence of systemic diseases known to affect periodontal health (e.g., diabetes, cardiovascular diseases)
* No infectious diseases such as tuberculosis, hepatitis, or AIDS
* Age 18 years or older
* Not pregnant (for female participants)

Exclusion Criteria:

* Pregnancy or ongoing lactation
* History of gingival treatment within the past 6 months
* History of any disease involving the oral mucosa (e.g., lichen planus, pemphigus vulgaris, chronic ulcerative stomatitis)
* Current use of systemic corticosteroids, immunosuppressive agents, or biological drugs
* History of systemic inflammatory diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, irritable bowel syndrome, diabetes mellitus)
* Fewer than 20 natural teeth (excluding third molars)
* Current smokers
* Age younger than 18 or older than 65 years

Primary outcomes:
measure: TNF-α levels in saliva
timeFrame: at baseline (single visit)
measure: TNF-α levels in serum
timeFrame: at baseline (single visit)
measure: IL-17A levels in saliva
timeFrame: at baseline (single visit)
measure: IL-17A levels in serum
timeFrame: at baseline (single visit)
measure: YKL-40 levels in saliva
timeFrame: at baseline (single visit)
measure: YKL-40 levels in serum
timeFrame: at baseline (single visit)
Secondary outcomes:
measure: periodontal assesment
timeFrame: at baseline (single visit)
measure: Periodontal Assesment
timeFrame: Baseline (at single visit)
measure: Periodontal Assesment
timeFrame: Baseline (at single visit)
measure: Periodontal Assessment
timeFrame: Baseline (at single visit)
Other outcomes:
Locations:
city: Antalya
country: Turkey
facility: Akdeniz University, Fculty of Dentistry, Akdeniz University Hospital
Study officials:
affiliation: Akdeniz Universty, Faculty Of Dentistry, Department Of Periodontology
name: Hazal DURMUS, DDS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kong Y, Zhang S, Su X, Peng D, Su Y. Serum levels of YKL-40 are increased in patients with psoriasis: a meta-analysis. Postgrad Med. 2019 Aug;131(6):405-412. doi: 10.1080/00325481.2019.1643634. Epub 2019 Jul 22.
citation: Martinez-Garcia M, Hernandez-Lemus E. Periodontal Inflammation and Systemic Diseases: An Overview. Front Physiol. 2021 Oct 27;12:709438. doi: 10.3389/fphys.2021.709438. eCollection 2021.
citation: de Oliveira PS, Cardoso PR, Lima EV, Pereira MC, Duarte AL, Pitta Ida R, Rego MJ, Pitta MG. IL-17A, IL-22, IL-6, and IL-21 Serum Levels in Plaque-Type Psoriasis in Brazilian Patients. Mediators Inflamm. 2015;2015:819149. doi: 10.1155/2015/819149. Epub 2015 Aug 13.
citation: Jimenez C, Carvajal D, Hernandez M, Valenzuela F, Astorga J, Fernandez A. Levels of the interleukins 17A, 22, and 23 and the S100 protein family in the gingival crevicular fluid of psoriatic patients with or without periodontitis. An Bras Dermatol. 2021 Mar-Apr;96(2):163-170. doi: 10.1016/j.abd.2020.08.008. Epub 2021 Jan 25.
citation: Marruganti C, Gaeta C, Falciani C, Cinotti E, Rubegni P, Alovisi M, Scotti N, Baldi A, Bellan C, Defraia C, Fiorino F, Valensin S, Bellini E, De Rosa A, D'Aiuto F, Grandini S. Are periodontitis and psoriasis associated? A pre-clinical murine model. J Clin Periodontol. 2024 Aug;51(8):1044-1053. doi: 10.1111/jcpe.13996. Epub 2024 May 3.