Study of the Effector Function of Regulatory T Cells and the Th2/Treg in Patients With Allergic Conjunctivitis With and Without Desensitization Treatment
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- To evaluate the effector function and the expression of TIGIT and PD-1 molecules on regulatory T cells, as well as the Th2/Treg, in patients with allergic conjunctivitis with and without allergen-specific immunotherapy, and in healthy control subjects.
研究概览
简要总结
This study aims to evaluate the effector function and expression of TIGIT and PD-1 on Tregs, as well as the Th2/Treg ratio, in patients with allergic conjunctivitis with and without desensitization therapy, compared to healthy controls.
Peripheral blood and tear samples will be collected once at enrollment. Treg and Th2 populations will be immunophenotyped, TIGIT and PD-1 expression assessed, and functional assays performed. Cytokine and antibody (IgE, IgG4) concentrations will be measured in serum and tears.
Results will be analyzed using descriptive statistics, Shapiro-Wilk test for distribution, t-tests or ANOVA for group comparisons, and correlation analyses for associations, with p<0.05 considered significant. This study seeks to identify immunological markers associated with disease severity and treatment response, potentially informing future therapeutic strategies.
详细描述
Allergic conjunctivitis is a prevalent ocular condition affecting approximately 10-20% of the global population, with 40-60% of allergic individuals exhibiting ocular symptoms. It is characterized by redness, itching, burning, and tearing, which result from excessive activation of immune response cells. Severe forms can significantly impact vision and quality of life, particularly in children, adolescents, and young adults. The disease is mediated by hypersensitivity reactions: Th2 lymphocytes release cytokines (IL-4, IL-5, IL-13) that stimulate IgE production by B lymphocytes. IgE binds to mast cells and induces the release of pro-inflammatory mediators upon allergen recognition. Regulatory T cells (Tregs) play a critical role in maintaining immune homeostasis by suppressing the activation and proliferation of effector T cell subsets, including Th1, Th2, Th9, and Th17, via cell-surface molecules such as TIGIT, LAP-TGF-β, and PD-1. Additionally, Tregs produce IL-10, which suppresses IgE production and induces IgG4 secretion by B cells. Allergen-specific immunotherapy (desensitization) has been employed to reduce symptoms and prevent recurrence in allergic diseases.
Rationale:
Allergic conjunctivitis is a public health concern that affects the quality of life of a substantial portion of the Mexican population. Immunological imbalances between effector T cells and Tregs have been reported. Understanding the balance of these subpopulations and the role of TIGIT and PD-1 molecules in Treg functional status is critical to elucidating disease mechanisms. Moreover, it is important to determine whether desensitization therapy induces changes in the Th2/Treg ratio and modulates TIGIT and PD-1 expression, which could serve as biomarkers of treatment response or therapeutic targets.
Hypothesis:
The effector function and expression of TIGIT and PD-1 on Tregs are decreased in patients with allergic conjunctivitis and are enhanced following desensitization therapy.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 5 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects aged between 5 and 30 years, of either sex.
- •Subjects with a confirmed diagnosis of allergic conjunctivitis.
- •Presence of active symptoms.
- •Positive skin tests.
- •Willingness to participate in the protocol by signing informed consent.
排除标准
- •Subjects who have had an infection within the two months prior to sample collection.
- •Patients with other active systemic allergic diseases (such as bronchial asthma, dermatitis, among others).
- •Subjects with chronic-degenerative or autoimmune diseases.
- •Subjects who have received topical immunosuppressive treatment in the last two months.
- •Subjects receiving systemic immunosuppressive therapy.
结局指标
主要结局
To evaluate the effector function and the expression of TIGIT and PD-1 molecules on regulatory T cells, as well as the Th2/Treg, in patients with allergic conjunctivitis with and without allergen-specific immunotherapy, and in healthy control subjects.
时间窗: At baseline (single assessment at enrollment in all study and control groups)
Patients with allergic conjunctivitis, both with and without desensitization treatment, as well as healthy subjects as a control group, will be included in the study. Peripheral blood and tear samples will be collected from all participants. Peripheral blood samples will be used for immunophenotyping of Treg and Th2 lymphocytes and for assessing the expression levels of the effector molecules TIGIT and PD-1.
Proportion of Treg and Th2 lymphocytes and Th2/Treg ratio in peripheral blood
时间窗: At baseline (single assessment at enrollment in all study and control groups)
Peripheral blood mononuclear cells will be immunophenotyped to quantify Treg and Th2 populations and calculate the Th2/Treg ratio.
Cytokine profile associated with Treg and Th2 lymphocytes in serum and tears
时间窗: At baseline (single assessment at enrollment in all study and control groups)
Concentrations of cytokines related to Treg (e.g., IL-10) and Th2 (e.g., IL-4, IL-5, IL-13) will be measured in serum and tear samples.
Effector function of Treg lymphocytes assessed by TIGIT and PD-1 expression and functional assays.
时间窗: At baseline (single assessment at enrollment in all study and control groups)
Treg cells will be analyzed for expression of effector molecules TIGIT and PD-1, and functional assays will be performed to assess suppressive capacity.
次要结局
- Concentration of IgE and IgG4 antibodies in serum and tears(At baseline (single assessment at enrollment in all study and control groups))
- Correlation of immunological parameters with ocular symptom severity and treatment response(At enrollment (clinical evaluation performed once in all study and control groups))
研究者
María C. Jiménez Martínez
Head of the Immunology Department, Research Unit
Instituto de Oftalmología Fundación Conde de Valenciana