Treg Effector Function and Th2/Treg Ratio in Allergic Conjunctivitis: Effect of Desensitization Therapy

NCT ID: NCT07171307

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2026-01-01
• Study Completion Date: 2026-09-30

Brief Summary

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.

Detailed Description

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.

Objectives:

The primary objective is to evaluate the effector function and expression of TIGIT and PD-1 on Tregs and the Th2/Treg ratio in patients with allergic conjunctivitis with and without desensitization therapy, compared to healthy controls. Secondary objectives include assessing correlations between immunological parameters and clinical severity of ocular symptoms and response to treatment.

Study Design and Methods:

This observational, cross-sectional, case-control study will include patients with allergic conjunctivitis, with or without desensitization therapy, and healthy control subjects. Peripheral blood and tear samples will be collected once at enrollment. Peripheral blood mononuclear cells will undergo immunophenotyping to quantify Treg and Th2 populations and assess TIGIT and PD-1 expression. Tregs will be isolated for functional assays. Cytokine concentrations associated with Th2 and Treg cells, as well as IgE and IgG4 levels, will be measured in serum and tears.

Statistical Analysis:

Descriptive statistics will summarize participant characteristics and study outcomes. The Shapiro-Wilk test will assess data distribution. Comparisons between two groups will use t-tests (parametric or non-parametric), and comparisons among more than two groups will use ANOVA (parametric or non-parametric). Correlation analyses will evaluate associations between immunological parameters and clinical outcomes. A p-value <0.05 will be considered statistically significant.

Conditions

Conjunctivitis, Allergic

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Conjunctivitis Allergic with allergen-specific immunotherapy (AIT)

The study subjects will be patients with a confirmed diagnosis of allergic conjunctivitis, active symptoms, and positive skin tests, who do not present any other type of systemic or local disease or inflammatory process and who are receiving allergen-specific immunotherapy (AIT).

No interventions assigned to this group

Conjunctivitis Allergic without allergen-specific immunotherapy (AIT)

The study subjects will be patients with a confirmed diagnosis of allergic conjunctivitis, active symptoms, and positive skin tests, who do not present any other type of systemic or local disease or inflammatory process, and who are not receiving immunotherapy treatment.

No interventions assigned to this group

Control group

The control subjects will be clinically healthy individuals, with a normal ocular surface and no evidence of active ocular disease or local or systemic inflammatory or infectious processes.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Instituto de Oftalmología Fundación Conde de Valenciana

OTHER

Sponsor Role: lead

Responsible Party

María C. Jiménez Martínez

Head of the Immunology Department, Research Unit

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Instituto de Oftalmología FAP Conde de Valenciana, IAP Sede Centro

Mexico City, Mexico City, Mexico

Countries

Mexico

Central Contacts

María del Carmén Jiménez Martínez

Role: CONTACT

mcjimenezm@institutodeoftalmologia.org

5554421700

References

Kucuksezer UC, Ozdemir C, Cevhertas L, Ogulur I, Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy and allergen tolerance. Allergol Int. 2020 Oct;69(4):549-560. doi: 10.1016/j.alit.2020.08.002. Epub 2020 Sep 6.

Reference Type: BACKGROUND

PMID: 32900655 (View on PubMed)

Calzada D, Baos S, Cremades-Jimeno L, Cardaba B. Immunological Mechanisms in Allergic Diseases and Allergen Tolerance: The Role of Treg Cells. J Immunol Res. 2018 Jun 14;2018:6012053. doi: 10.1155/2018/6012053. eCollection 2018.

Reference Type: BACKGROUND

PMID: 30013991 (View on PubMed)

Other Identifiers

CI-032-2024

Identifier Type: OTHER

Identifier Source: secondary_id

CB-031-2024

Identifier Type: OTHER

Identifier Source: secondary_id

CEI-2024/06/16

Identifier Type: -

Identifier Source: org_study_id