Identification of B Regulatory Cells by Flow Cytometry

December 4, 2025 updated by: Hull University Teaching Hospitals NHS Trust

Identification and Quantitation of Human B Regulatory Cells Via Flow Cytometry and Their Potential Role as a Treatment Efficacy Biomarker in Allergen-specific Immunotherapy

The goal of this laboratory and observational study is to develop a test to quantify B-regulatory cells in blood. This will be used to detect changes in B-regulatory cell populations in pollen and insect venom allergic patients who are receiving routine allergen immunotherapy treatment. The primary question this study aims to answer is;

1). Are changes in blood B-regulatory cells associated with successful allergen immunotherapy treatment, and therefore do these changes suggest patients have developed a suitable level of allergen tolerance and reduction in their allergic symptoms upon re-exposure to the causal allergen.

Patients will also be asked to complete quality of life questionnaire periodically throughout the study to determine if there are associations between variation in B-regulatory cell populations in blood and allergic symptoms experienced.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Allergen immunotherapy (AIT) is a disease-modifying treatment for allergic disease which promotes immune system tolerance, i.e. reduces clinical manifestations of allergy and is the only known effective treatment to prevent anaphylaxis in patients who have previously had serious reactions to insect venoms. AIT induces a variety of immune system changes to facilitate this process, one mechanism of which is the production of a population of white blood cells called B-regulatory cells (BREGs). These cells release a chemical called interleukin-10 (IL-10) which inhibits (controls) the allergic immune response. The success of AIT is difficult to establish/monitor during treatment. Often treatment success can only be established at the end of a long treatment period (typically 3 years) and currently clinicians rely on patient symptoms upon re-exposure to further allergen post-treatment. Therefore there is a requirement to identify a marker (biomarker) which can be tested for during treatment to help clinicians establish at an earlier time, if the AIT is showing success or if a change to treatment is required. This research will measure the BREG and IL-10 production in patients before and at multiple points during AIT, to establish if there is a relationship between the BREG/IL-10 concentration and the success or failure of AIT in controlling patient symptoms of allergy. The hope is that BREG measurement could be used in the future as a biomarker for AIT efficacy, and therefore provide evidence of AIT success sooner than current protocols, or establishing failure of AIT and therefore expediting a change in treatment. The latter will likely result in saving time in pursuing a treatment which is not working, but also for understanding when the treatment has already reached optimal effectiveness and can be stopped.

Overall Aim:

To develop a flow cytometry assay for the identification and quantitation of human B regulatory cells to allow evaluation of their potential role as a treatment efficacy biomarker in allergen-specific immunotherapy.

Primary Objectives:

  1. Identification of a biomarker that defines success of allergen immunotherapy
  2. Development of a novel flow cytometry assay to detect and quantify B-regulatory cells in whole blood/peripheral blood mononuclear cell (PBMC) isolate
  3. Determine the reference intervals for BREG cell quantitation in the test and control groups using conventional parametric or non-parametric measures, depending on the characteristics of the data obtained

Secondary Objectives:

  1. Evaluation of the performance of the flow cytometry methods as per usual laboratory protocol
  2. Comparison of BREG cell quantitation in the control group verses the test group, and the test group at baseline verses on AIT
  3. Comparison of BREG cell quantitation in patients receiving subcutaneous and sublingual AIT
  4. Comparison of allergen-specific blocking antibodies (allergen-specific IgG4) in the test group at baseline and in those on AIT
  5. Assess correlation of allergen-specific blocking antibody quantitation with changes in whole blood B regulatory cell concentrations

Study Type

Observational

Enrollment (Estimated)

80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
    • East Yorkshire
      • Hull, East Yorkshire, United Kingdom, HU3 2JZ
        • Hull Teaching Hospital NHS Trust
        • Contact:
        • Contact:
        • Principal Investigator:
          • Kristina Emsell-Needham, BSc, MSc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Participants routinely attending the Immunology and Allergy Clinical at Hull University Teaching Hospitals Test cohort patients - selected from patients who meet eligibility criteria of the study, and who are starting routine allergen immunotherapy as part of their routine care outside of the study Allergen immunotherapy candidates to receive venom (bee/wasp), house dust mite or pollen immunotherapy only to be included in the study

Description

Control cohort - Participants with:

  • No clinical and laboratory findings of IgE-mediated hypersensitivity (i.e. no clinical history of specific allergies to pollens, house dust mite or insect venoms
  • Negative serological testing for specific IgE to pollens, house dust mite and insect venoms
  • Patients aged 18 years or older

Test cohort:

  • Participants over the age of 18 years
  • Participants with physician-diagnosed IgE-mediated allergic disease to pollens, house dust mite or insect venoms

Exclusion Criteria:

  • Patients under the age of 18 years
  • Samples from patients with IgE-mediated allergic disease, treated or untreated, specific to allergens other than pollens, house dust mite and insect venom
  • Participants who are pregnant
  • Participants who cannot adequately understand verbal and / or written explanations given in English

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Control Cohort
  • Participants routinely attending the Immunology and Allergy Clinical at Hull University Teaching Hospitals
  • Participants over the age of 18 years
  • Participants with no clinical and laboratory findings of IgE-mediated hypersensitivity (i.e. no clinical history of specific allergies to pollens, house dust mite or insect venoms, negative serological testing for specific IgE to pollens, house dust mite and insect venoms)
Diagnostic test: Venepuncture
Whole blood flow cytometry analysis of T-/B-lymphocyte subsets, regulatory B cells and regulatory T cells. Serological detection (immunoassay) of allergen-specific IgE and IgG4
Test Cohort
  1. Participants routinely attending the Immunology and Allergy Clinical at Hull University Teaching Hospitals
  2. Participants over the age of 18 years
  3. Participants with physician-diagnosed IgE-mediated allergic disease to pollens, house dust mite or insect venoms

  4. Participants who are eligible to commence allergen immunotherapy (AIT). AIT will comprise;

    • Sublingual immunotherapy (SLIT) Grazax for grass pollen allergy or Acarizax for house dust mite allergy
    • Subcutaneous immunotherapy (SCIT) Venom immunotherapy involving subcutaneous injections against bee or wasp venoms (as per schedule following conventional or modified rush protocols)

AIT eligibility decided upon through combination of clinical assessment, multi-disciplinary team (MDT) meeting discussion and BSACI guidance.
Diagnostic test: Venepuncture
Whole blood flow cytometry analysis of T-/B-lymphocyte subsets, regulatory B cells and regulatory T cells. Serological detection (immunoassay) of allergen-specific IgE and IgG4
Drug: Allergen Specific Immunotherapy
Test group receiving venom allergen immunotherapy as part of standard and routine care pathway (treatment commencement NOT for study purposes, cohort selected of those who are routinely commencing treatment).
Drug: Allergen Specific Immunotherapy
Test group receiving pollen allergen immunotherapy as part of standard and routine care pathway (treatment commencement NOT for study purposes, cohort selected of those who are routinely commencing treatment).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Utility of B regulatory cells as a biomarker of AIT treatment sucess
Time Frame: From enrolment to 1 year post commencing allergen-specific immunotherapy treatment
To assess whether an increase in regulatory B cell concentration is a useful biomarker to indicate AIT treatment success and specific allergen de-sensitisation.
From enrolment to 1 year post commencing allergen-specific immunotherapy treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Develop a flow cytometry laboratory assay for the detection of B regulatory cells
Time Frame: From study commencement (planned May 2025) to end of study data collection (planned May 2027)
Development of a flow cytometry protocol that accurately detects and quantifies the regulatory B cell populations
From study commencement (planned May 2025) to end of study data collection (planned May 2027)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hull University Teaching Hospitals NHS Trust

Collaborators

University of Manchester
Health Education England, Wessex

Investigators

  • Principal Investigator: Kristina Emsell-Needham, BSc, MSc, Hull University Teaching Hospitals NHS Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 1, 2026

Primary Completion (Estimated)

April 28, 2027

Study Completion (Estimated)

July 31, 2027

Study Registration Dates

First Submitted

March 10, 2025

First Submitted That Met QC Criteria

March 13, 2025

First Posted (Actual)

March 14, 2025

Study Record Updates

Last Update Posted (Actual)

December 5, 2025

Last Update Submitted That Met QC Criteria

December 4, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRAS ID 345343

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No current plans to make IPD fully available to other researches at this time

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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