Clinical Trials

Tolerance in Beekeepers

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	Yes
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06156046
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University Hospital Plymouth NHS Trust
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Bee Sting

Additional Details

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.

Arms & Interventions

Arms

: Group 1

Individuals naïve to beekeeping (<2 previous bee stings, non in the last 24 months). No history of anaphylaxis

: Group 2

Beekeepers with > approximately 10 stings/year who have been beekeeping for >3 years. No history of anaphylaxis.

: 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)

Interventions

Diagnostic Test: - skin prick test

Skin prick test for bee venom

Diagnostic Test: - Blood tests

IgE/G and T cell tolerance studies

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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