The Impact of Pollutants on Patients With Psoriasis or Atopic Dermatitis by Investigating the Activation of the Aromatic Hydrocarbon Receptor.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 64
- 主要终点
- Determination of CYP 1A1/1B1 in PBMCs
研究概览
简要总结
Introduction Pollution is a significant public health issue. Research has shown a positive correlation between air pollution and chronic inflammatory dermatoses, including psoriasis and eczema. The incidence of these diseases has been steadily increasing since the beginning of industrialization. The mechanism behind this association involves the activation of the aromatic hydrocarbon receptor (AhR). The aryl hydrocarbon receptor (AhR) plays a role in regulating the balance between T helper 17 (TH17) and regulatory T cells (TREG), as well as in generating oxidative stress and producing pro-inflammatory cytokines. Studies in cultured keratinocytes have shown that a non-competitive antagonist that modulates AhR activity can reduce cutaneous inflammatory processes induced by polycyclic aromatic hydrocarbons (PAHs).
Objectives:
It has been suggested that activation of the AhR by PAHs and dioxins may be related to the pathogenesis of atopic dermatitis and psoriasis. The main objective is to compare the levels of AhR pathway activation markers between cases and controls. Secondary objectives include correlating environmental exposure to AhR ligands with disease severity in patients. Finally, we will compare the expression of inflammatory and AhR activation markers in cultured peripheral blood mononuclear cells (PBMCs) after in vitro stimulation with benzo(a)pyrene.
Material and methods:
The study will measure exposure to pollutants by determining blood dioxins and urinary PAH metabolites. Pro-inflammatory cytokines IL1β, TNFα, IL23, IL17 and IFNγ and Malondialdehyde (MDA) serum concentrations will be measured by ELISA. The TREG and TH17 lymphocyte population ratio will be evaluated by flow cytometry on isolated PBMCs. Additionally, the level of expression of CYP 1A1 and 1B1, pollutant-metabolizing enzymes induced by AhR, will be assessed on isolated PBMCs. The expression levels of the AhR and NfkB active fractions will be determined by immunofluorescence. Subsequently, levels of AhR activation markers will be compared after stimulation of PBMCs with benzo(a)pyrene.
详细描述
I. Introduction Pollution is a significant component of the exposome, with established links to human health. In 2019, pollution was estimated to be responsible for 9 million premature deaths, making it the fourth leading risk factor for mortality worldwide. Over the last 20 years, pollution-related deaths have increased by 66%. This is due to industrialization, uncontrolled urbanization, population growth, burning fossil fuels, and a lack of restrictive policies in some regions.
The cutaneous layer is composed of a complex network of cells that form a mechanical and biological barrier essential for maintaining the body's integrity and homeostasis. Pollution can directly impair this function by crossing the barrier or entering the systemic circulation through inhalation or ingestion.
Atopic dermatitis (AD) and psoriasis are chronic inflammatory skin conditions with multifactorial origins, including genetic predisposition, immune dysregulation, and environmental factors. Epidemiological studies have shown a positive correlation between air pollution and the development of these diseases.
Given their high prevalence and the impact of symptoms on patients' quality of life, a better understanding of the exposome in these diseases represents a major challenge.
Experimental studies have demonstrated that the aromatic hydrocarbon receptor (AhR) pathway plays a significant role in the impact of pollutants on psoriasis and AD. AhR is a transcription factor involved in the response to environmental pollutants, which remains inactive in a cytoplasmic complex with chaperone proteins. Upon binding with its ligand, AhR translocates to the nucleus and dimerizes with its nuclear partner, Arnt. The activation of the complex leads to the expression of numerous genes that contain a consensus sequence known as the xenobiotic response element (XRE) in their promoters.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18 to
- •The study's participants possess the capacity to comprehend the research.
- •Patients have consulted or been hospitalized for dermatological reasons
- •Patients undergo biological monitoring as part of their routine care.
- •Having psoriasis or atopic dermatitis for more than 6 weeks (cases)
- •Subjects with a PASI severity score (psoriasis) greater than 5 and an EASI score (atopic dermatitis) greater than 12 at inclusion (cases)
排除标准
- •Active smoking or less than 3 months since quitting
- •Pregnancy
- •Biotherapy treatment in progress or in the 8 weeks prior to inclusion
- •Immunotherapy treatment in progress or in the 6 months prior to inclusion
- •Chemotherapy treatment in progress or in the 4 weeks prior to inclusion
- •Person in an emergency situation, adult subject to a legal protection measure (adult under guardianship, curatorship or safeguard of justice).
- •Non-affiliation with a social security scheme (beneficiary or dependent).
- •Subjects with a history of autoimmune diseases (controls)
结局指标
主要结局
Determination of CYP 1A1/1B1 in PBMCs
时间窗: Inclusion
The expression of CYP1A1 and CYP1B1 in PBMCs in ng/mL is used as primary endpoint;
次要结局
未报告次要终点