- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06156046
Tolerance in Beekeepers
Elucidation of the Mechanism of Immune Tolerance in Beekeepers
Beekeepers experience multiple bee stings each year. Many of these beekeepers (25-60%) become sensitized to bee venom through the production of specific antibodies that target the bee venom. Although these antibodies are important in the triggering of an allergic reaction only a small number of sensitised beekeepers go on to have an allergic reaction with symptoms away from the site of the sting. These reactions can be severe and are known as anaphylactic reactions.
The study investigates why some beekeepers develop severe allergic symptoms after bee stings while others do not.
This study will explore factors in the blood that protect sensitised individuals from having anaphylactic reactions - meaning that despite being sensitised they are tolerant and do not react to subsequent stings.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Beekeepers experience multiple stings each year many of whom (25-60%) become sensitised to bee (apis mellifera) venom through the production of IgE antibodies (1,2). However only a small proportion of the sensitised group go on to have anaphylaxis to bee venom. This study will investigate differences in T cell tolerance to bee venom in 3 groups by exploring factors that "protect" sensitised individuals from having anaphylactic reactions - meaning that despite being sensitised they are tolerant and do not react to subsequent stings.
T regulatory cell (Tregs) play a critical role in promoting immune tolerance to allergens and Treg generation has been shown to occur in bee venom allergic individuals following venom desensitisation therapy (3.4). Observations in sensitised tolerant (non-allergic) beekeepers (TB) suggest that exposure to venom through bee stings results in a similar increase in the frequencies of induced Tregs (iTregs) (5). Helios negative induced Treg cells have also been suggested to contribute significantly to the establishment of immune tolerance in beekeepers. We will analyse the differences in Treg and Teffector (Teff) populations comparing sensitised beekeepers who are able to tolerate venom exposure (sensitised, tolerant beekeepers TB) with those beekeepers who do develop symptoms of systemic allergic reactions following bee sting (AB). A group of non-sensitised (NS) individuals will be recruited as a control population. We will perform RNA-seq to analyse the gene expression in Treg cells and Teff cells from all three groups. This will help to identify molecular targets that are involved in inducing the allergic reaction and also the genes that are involved in suppressing this reaction.
Considering the outcome of tolerance or anaphylaxis following bee stings, and the role of Treg and Teff cells in these processes, we will investigate the epigenetic regulations involved, which determine these cell's function. RNA-seq analysis will provide critical information about the genes involved in allergic reaction or in its suppression. DNA and histone modification analyses in the regulatory regions of these genes will help to better understand the underlying mechanism.
This project will investigate why some beekeepers who are sensitised to bee venom are able to tolerate bee stings, while in other sensitised individuals a bee sting can lead to life threatening anaphylaxis. This is not only of significance to beekeepers, but also has potential implications for the understanding of allergen tolerance in other allergic disease.
Study Type
Enrollment (Estimated)
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Group 1 inclusion criteria. Individuals naive to beekeeping (<2 previous bee stings, none in the last 24 months).
No history of anaphylaxis to bee stings.
Group 2 inclusion criteria. Beekeepers with > approximately 10 stings/year who have been beekeeping for >3 years.
No history of anaphylaxis to bee stings.
Group 3 inclusion criteria Beekeepers with diagnosis of anaphylaxis to bee venom in the last 12 months who are sensitised to bee venom (as evidenced by positive specific IgE and positive skin test to bee venom).
Description
Inclusion Criteria:
- Group 1 inclusion criteria.
- Individuals naive to beekeeping (<2 previous bee stings, none in the last 24 months)
- no history of anaphylaxis to stings. Group 2 inclusion criteria.
- Beekeepers with > approximately 10 stings/year who have been beekeeping for >3 years.
- No history of anaphylaxis to bee venom. Group 3 inclusion criteria
- Beekeepers with diagnosis of anaphylaxis to bee venom in the last 12 months who are sensitised to bee venom (as evidenced by positive specific IgE and positive skin test to bee venom)
Exclusion Criteria:
- Unable to understand protocol/consent.
- Unable to commit to follow up visits.
- Participants with a known history of mastocytosis or under investigation for suspected mastocytosis.
- Participants undergoing desensitisation treatment to bee venom before the first visit.
- Participants being treatment with immunosuppressive medications. being treatment with immunosuppressive medications.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Group 1
Individuals naïve to beekeeping (<2 previous bee stings, non in the last 24 months).
No history of anaphylaxis
|
Skin prick test for bee venom
IgE/G and T cell tolerance studies
|
Group 2
Beekeepers with > approximately 10 stings/year who have been beekeeping for >3 years.
No history of anaphylaxis.
|
Skin prick test for bee venom
IgE/G and T cell tolerance studies
|
Group 3
Beekeepers with diagnosis of anaphylaxis to bee venom in the last 12 months who are sensitised to bee venom ( as evidenced by positive IgE and positive skin test to bee venom)
|
Skin prick test for bee venom
IgE/G and T cell tolerance studies
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cell types
Time Frame: 3 years
|
Number and function of various cell types will be measured for each participant
|
3 years
|
Molecular and epigenetic profiles
Time Frame: 3 years
|
Molecular and epigenetic profiles will be measured in each participant
|
3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sensitisation data
Time Frame: 3 years
|
results of sensitisation data from the beginning and end of the beekeeping season will be compared
|
3 years
|
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- 330722
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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