Bee StingNCT06156046
Tolerance in Beekeepers
An observational study of Bee Sting, run by University Hospital Plymouth NHS Trust at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Bee Sting
- What is being tested?
- skin prick test and Blood tests
- How many people
- 120 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 22 Jan 2024to 1 Oct 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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).
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Derriford Hospital - University Hospitals Plymouth
Plymouth, Devon, PL65FP
Jane Evely, +44 01752 431816, j.evely@nhs.net
Claire Bethune
About this study
Official title: 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.
Read the 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. 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. 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). 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.
- Conditions
- Bee Sting
- Being tested
- skin prick test, Blood tests
- Keywords
- Immune tolerance, Anaphylaxis, Beekeepers
- Medical subject headings
- Anaphylaxis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
skin prick testDiagnostic test
Skin prick test for bee venom
Blood testsDiagnostic test
IgE/G and T cell tolerance studies
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Individuals naïve to beekeeping (<2 previous bee stings, non in the last 24 months). No history of anaphylaxis Receives: Diagnostic Test: skin prick test; Diagnostic Test: Blood tests | |
| Group 2 | Beekeepers with > approximately 10 stings/year who have been beekeeping for >3 years. No history of anaphylaxis. Receives: Diagnostic Test: skin prick test; Diagnostic Test: Blood tests | |
| 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) Receives: Diagnostic Test: skin prick test; Diagnostic Test: Blood tests |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cell comparison
(i) To compare the number of various cell (CD4+, CD8+ and Treg etc.) populations in the non-sensitised control population (NS), the sensitised but tolerant beekeepers (TB) and the allergic beekeeper (AB) population.
Measured: 3 years
Cellular function
(ii) To identify differences in cellular function in the non-sensitised control population (NS), the sensitised but tolerant beekeepers (TB) and the allergic beekeeper (AB) population.
Measured: 3 years
Molecular mechanism
(iii) To elucidate the molecular mechanism and the differences observed in (i) and (ii).
Measured: 3 years
Epi regulation
(iiii) To elucidate the epigenetic regulation underpinning and the differences observed in (i) and (ii)
Measured: 3 years
Secondary outcomes (2)
Sensitisation data- skin prick testing
To compare results of skin prick testing from the beginning and end of the beekeeping season.
Measured: 3 years
Sensitisation data - specific IgE's in blood
To compare results of specific IgE's in blood from the beginning and end of the beekeeping season.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2023
- Study start22 Jan 2024
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bee StingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Plymouth NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Plymouth
- Responsible party
- Sponsor
- Investigators
- Claire Bethune, Principal investigator, University Hospitals Plymouth
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06156046
- Sponsor's protocol ID
- 330722
- Status last verified
- Sep 2026
- First submitted
- 24 Nov 2023
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Elucidation of the Mechanism of Immune Tolerance in Beekeepers
- ClinicalTrials.gov ID
- NCT06156046
- Acronym / sponsor ID
- 330722
- Conditions
- Bee Sting
- Keywords
- Immune tolerance, Anaphylaxis, Beekeepers
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University Hospital Plymouth NHS TrustUniversity, hospital or other
- Collaborators
- University of Plymouth
- Study start
- 22 Jan 2024 (actual)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 Oct 2027 (estimated)
- First posted
- 5 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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. 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. 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). 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 design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | Diagnostic Test: skin prick test, Diagnostic Test: Blood testsIndividuals naïve to beekeeping (<2 previous bee stings, non in the last 24 months). No history of anaphylaxis |
| Group 2 | – | Diagnostic Test: skin prick test, Diagnostic Test: Blood testsBeekeepers with > approximately 10 stings/year who have been beekeeping for >3 years. No history of anaphylaxis. |
| Group 3 | – | Diagnostic Test: skin prick test, Diagnostic Test: Blood testsBeekeepers 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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).
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| skin prick testSkin prick test for bee venom | Diagnostic test | Group 1, Group 2, Group 3 |
| Blood testsIgE/G and T cell tolerance studies | Diagnostic test | Group 1, Group 2, Group 3 |
Primary outcome
Cell comparison
Time frame: 3 years
(i) To compare the number of various cell (CD4+, CD8+ and Treg etc.) populations in the non-sensitised control population (NS), the sensitised but tolerant beekeepers (TB) and the allergic beekeeper (AB) population.
Cellular function
Time frame: 3 years
(ii) To identify differences in cellular function in the non-sensitised control population (NS), the sensitised but tolerant beekeepers (TB) and the allergic beekeeper (AB) population.
Molecular mechanism
Time frame: 3 years
(iii) To elucidate the molecular mechanism and the differences observed in (i) and (ii).
Epi regulation
Time frame: 3 years
(iiii) To elucidate the epigenetic regulation underpinning and the differences observed in (i) and (ii)
2 secondary outcomes
Sensitisation data- skin prick testing
Time frame: 3 years
Sensitisation data - specific IgE's in blood
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2026.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Claire Bethune principal investigator
University Hospitals Plymouth
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Bee Sting, run by University Hospital Plymouth NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jane Evely (441752431816, j.evely@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cell comparison (time frame: 3 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2026.