Diagnostic markers of clinical allergy versus sensitisation to peanut
Lead Research Organisation:
King's College London
Department Name: Asthma Allergy and Lung Biology
Abstract
Peanut allergy (PA) is particularly problematic since it is increasingly common in infants and
children, may be life-threatening, frequently persists through adulthood and has a significant impact
on children?s quality of life.
The diagnosis of PA is based on a combination of a history of allergic reaction(s) to peanut and
positive allergy tests. However, this is not reliable because many patients have positive allergy tests
and tolerate peanut whilst others have positive allergy tests and are peanut allergic. The only way to
clarify this is by giving the child peanuts in oral food challenges (OFC). However, OFC are expensive,
laborious and potentially dangerous, as they may induce allergic reactions.
Our proposed research project aims to provide fundamental insights into the mechanisms of
allergy and tolerance and also to distinguish between peanut allergic children and those who have
positive allergy tests but tolerate peanut without the need for OFC.
This project will improve allergy diagnosis, allowing for a more accurate distinction of allergic
children among children with positive allergy tests, not only to peanut but also to other allergens. By
understanding why some children with positive allergy tests react and others do not, we may
develop new definitive treatments for PA
children, may be life-threatening, frequently persists through adulthood and has a significant impact
on children?s quality of life.
The diagnosis of PA is based on a combination of a history of allergic reaction(s) to peanut and
positive allergy tests. However, this is not reliable because many patients have positive allergy tests
and tolerate peanut whilst others have positive allergy tests and are peanut allergic. The only way to
clarify this is by giving the child peanuts in oral food challenges (OFC). However, OFC are expensive,
laborious and potentially dangerous, as they may induce allergic reactions.
Our proposed research project aims to provide fundamental insights into the mechanisms of
allergy and tolerance and also to distinguish between peanut allergic children and those who have
positive allergy tests but tolerate peanut without the need for OFC.
This project will improve allergy diagnosis, allowing for a more accurate distinction of allergic
children among children with positive allergy tests, not only to peanut but also to other allergens. By
understanding why some children with positive allergy tests react and others do not, we may
develop new definitive treatments for PA
Technical Summary
Background: In the United Kingdom, 2% of primary school children will develop peanut allergy but
10% will develop serum specific IgE to peanut. This poses diagnostic difficulties and dangerous oral
food challenges(OFC) are required. Why is it that some patients have high serum specific IgE levels
to peanut and tolerate it and others have low specific IgE levels and react violently?
Hypotheses:
Two separate hypotheses will be addressed:
1. Peanut specific IgE is functionally different in allergic and tolerant children;
2. The functionality of peanut specific IgE is similar and sensitized but tolerant children have an
inhibitor that blocks IgE function.
Objectives:
1) To understand the immunological differences that underpin sensitization and allergy;
2) To improve the diagnosis of peanut allergy while reducing the need for OFC.
Study design:
Four groups of children will be compared:
- Peanut allergic(PA) ? peanut IgE positive and peanut allergic(n=25);
- Peanut sensitized(PS) ? peanut IgE positive, never reacted to peanut and eat peanut(n=25);
- Peanut allergy resolved(PR) ? peanut IgE positive and have outgrown peanut allergy(n=25);
- Non-allergic(NA) ? peanut IgE negative and eat peanut(n=25).
PA, PS and PR groups will be matched for serum peanut specific IgE levels.
Methodology:
To test the first hypothesis, we will:
- perform basophil mediator release assays(histamine, IL-4 and IL-13), following pre-incubation
with sera and subsequent stimulation with peanut extract;
- purify IgE from sensitised but tolerant children(PS and PR) and assess whether it induces
basophil histamine release;
- analyse peanut specific IgE for specificity and clonality(peanut peptide and epitope recognition
of IgE, using ImmunoCAPTM and microarray immunoassays) and for affinity and avidity(using
surface plasmon resonance).
To test the second hypothesis, we will:
- pool sera from sensitised but tolerant with sera from allergic children and assess whether
basophil mediator release is inhibited;
- purify antibody isotypes other than IgE(e.g IgG4) from sensitised but tolerant children and
assess whether basophil mediator release is inhibited;
- assess basophil intracellular signalling protein activities, excitatory(Syk and p38-MAPK) and
inhibitory(SHIP), on western blotting, in case an inhibition is observed.
Scientific and medical opportunities:
This study will extend our knowledge about the mechanisms that determine clinical reactivity to
peanut in sensitized patients and define superior diagnostic markers for peanut allergy. The results
may be extended to other food and respiratory allergens. By understanding why some IgE react and
other do not, we may target therapeutical strategies to induce tolerance and provide definitive
treatment for allergy.
10% will develop serum specific IgE to peanut. This poses diagnostic difficulties and dangerous oral
food challenges(OFC) are required. Why is it that some patients have high serum specific IgE levels
to peanut and tolerate it and others have low specific IgE levels and react violently?
Hypotheses:
Two separate hypotheses will be addressed:
1. Peanut specific IgE is functionally different in allergic and tolerant children;
2. The functionality of peanut specific IgE is similar and sensitized but tolerant children have an
inhibitor that blocks IgE function.
Objectives:
1) To understand the immunological differences that underpin sensitization and allergy;
2) To improve the diagnosis of peanut allergy while reducing the need for OFC.
Study design:
Four groups of children will be compared:
- Peanut allergic(PA) ? peanut IgE positive and peanut allergic(n=25);
- Peanut sensitized(PS) ? peanut IgE positive, never reacted to peanut and eat peanut(n=25);
- Peanut allergy resolved(PR) ? peanut IgE positive and have outgrown peanut allergy(n=25);
- Non-allergic(NA) ? peanut IgE negative and eat peanut(n=25).
PA, PS and PR groups will be matched for serum peanut specific IgE levels.
Methodology:
To test the first hypothesis, we will:
- perform basophil mediator release assays(histamine, IL-4 and IL-13), following pre-incubation
with sera and subsequent stimulation with peanut extract;
- purify IgE from sensitised but tolerant children(PS and PR) and assess whether it induces
basophil histamine release;
- analyse peanut specific IgE for specificity and clonality(peanut peptide and epitope recognition
of IgE, using ImmunoCAPTM and microarray immunoassays) and for affinity and avidity(using
surface plasmon resonance).
To test the second hypothesis, we will:
- pool sera from sensitised but tolerant with sera from allergic children and assess whether
basophil mediator release is inhibited;
- purify antibody isotypes other than IgE(e.g IgG4) from sensitised but tolerant children and
assess whether basophil mediator release is inhibited;
- assess basophil intracellular signalling protein activities, excitatory(Syk and p38-MAPK) and
inhibitory(SHIP), on western blotting, in case an inhibition is observed.
Scientific and medical opportunities:
This study will extend our knowledge about the mechanisms that determine clinical reactivity to
peanut in sensitized patients and define superior diagnostic markers for peanut allergy. The results
may be extended to other food and respiratory allergens. By understanding why some IgE react and
other do not, we may target therapeutical strategies to induce tolerance and provide definitive
treatment for allergy.
Organisations
- King's College London, United Kingdom (Collaboration, Fellow, Lead Research Organisation)
- Thermofisher - Uppsala (Collaboration)
- University of Edinburgh, United Kingdom (Collaboration)
- Antwerp University Hospital (Collaboration)
- Utrecht University (Collaboration)
- August Pi i Sunyer Biomedical Research Institute (Collaboration)
- University of Bonn, Germany (Collaboration)
- Royal Manchester Children's Hospital (Collaboration)
- Danaher Corporation (Collaboration)
- Queen Mary, University of London, United Kingdom (Collaboration)
- University Hospitals of Leicester NHS Trust, Leicester (Collaboration)
- King's College Hospital Charitable Trust, United Kingdom (Collaboration)
- University of Lisbon (Collaboration)
- University of Helsinki, Finland (Collaboration)
- Stanford University, United States (Collaboration)
- Valencia University, Spain (Collaboration)
- Benaroya Research Institute (Collaboration)
- Murdoch Children's Research Institute (Collaboration)
- Immune Tolerance Network (Collaboration)
- Southampton Hospital (Collaboration)
- Curie Institute Paris (Institut Curie) (Collaboration)
- Karolinska Institute, Sweden (Collaboration)
- Sandwell and West Birmingham Hospitals NHS Trust (Collaboration)
- University of Malaga (Collaboration)
- Imperial College London, United Kingdom (Collaboration)
- Viapath (Collaboration)
- Thermo Fisher Scientific (Collaboration)
- Federal University of São Paulo (Collaboration)
- Technical University of Munich (Collaboration)
- University of Geneva, Switzerland (Collaboration)
- National Institutes of Health, United States (Collaboration)
- University of Chicago, United States (Collaboration)
- Aarhus University, Denmark (Collaboration)
- Sheffield Children's Hospital (Collaboration)
- U.S. Department of Agriculture USDA (Collaboration)
- University College Hospital Ibadan (Collaboration)
- National Jewish Medical and Research Center, USA (Collaboration)
- Newcastle upon Tyne Hospitals NHS Foundation Trust (Collaboration)
- Charité - University of Medicine Berlin (Collaboration)
- Addenbrooke's Hospital (Collaboration)
Publications
Barber D
(2021)
Molecular allergology and its impact in specific allergy diagnosis and therapy.
in Allergy
Brough H
(2020)
Defining challenge-proven coexistent nut and sesame seed allergy: A prospective multicenter European study
in Journal of Allergy and Clinical Immunology
Brough H
(2021)
Early intervention and prevention of allergic diseases
in Allergy
Brough HA
(2020)
Reply.
in The Journal of allergy and clinical immunology
Brough HA
(2013)
Peanut protein in household dust is related to household peanut consumption and is biologically active.
in The Journal of allergy and clinical immunology
Buyuktiryaki B
(2020)
Food allergy severity predictions based on cellular in vitro tests.
in Expert review of molecular diagnostics
Caminati M
(2020)
The EAACI-AAAAI-WAO Junior Members' joint survey: A worldwide snapshot of Allergy and Clinical Immunology specialty.
in Allergy
Carboni E
(2020)
Les tests de provocation alimentaire dans 4 pays européens : France, Espagne, Italie et Royaume-Uni
in Revue Française d'Allergologie
Chan YC
(2014)
"Auto-anti-IgE": naturally occurring IgG anti-IgE antibodies may inhibit allergen-induced basophil activation.
in The Journal of allergy and clinical immunology
| Description | Chair of the Research and Outreach Committee Food Allergy Group of the European Academy of Allergy and Clinical Immunology |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a advisory committee |
| Description | EAACI Allergen-specific Immunotherapy Guidelines for Food Allergy |
| Geographic Reach | Europe |
| Policy Influence Type | Membership of a guideline committee |
| Description | EAACI Allergen-specific Immunotherapy Guidelines for Prevention of Allergic Disease |
| Geographic Reach | Europe |
| Policy Influence Type | Membership of a guideline committee |
| Description | EAACI Anaphylaxis Guidelines |
| Geographic Reach | Asia |
| Policy Influence Type | Membership of a guidance committee |
| Description | EAACI Food Allergy Guidelines |
| Geographic Reach | Asia |
| Policy Influence Type | Membership of a guidance committee |
| Description | EAACI Food Allergy Guidelines |
| Geographic Reach | Europe |
| Policy Influence Type | Membership of a guideline committee |
| Description | EAACI Position paper about clinical utility of the basophil activation test |
| Geographic Reach | Asia |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Description | EAACI Position paper establishing a new framework for the interpretation of IgE sensitisation tests |
| Geographic Reach | Asia |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Description | EAACI Task Force on Allergen Thresholds |
| Geographic Reach | Europe |
| Policy Influence Type | Membership of a guideline committee |
| Description | EAACI Taskforce on the external quality assurance of the basophil activation test |
| Geographic Reach | Europe |
| Policy Influence Type | Membership of a guideline committee |
| Description | Guidelines for food allergy and weaning |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
| Description | Mast Cell, Basophil & Eosinophil expert group of NIAID Asthma and Allergy Network Summit meeting |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Membership of a guideline committee |
| Description | WHO IUIS Allergen Nomenclature Committee Member |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Membership of a guideline committee |
| Description | ERA-HDHL Call for Joint Transnational Research Proposals: "Addressing adverse and beneficial effects of food ingredients and food processing on hypersensitivities to food" (FOOD_HYPERSENS) |
| Amount | £1,000,000 (GBP) |
| Funding ID | BB/X002519/1 |
| Organisation | King's College London |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 03/2022 |
| End | 03/2025 |
| Description | Food Allergy Research and Education |
| Amount | $500,000 (USD) |
| Organisation | Food Allergy Research and Education (FARE) |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 03/2021 |
| End | 04/2024 |
| Description | Immune Tolerance Network/NIAID |
| Amount | $320,420 (USD) |
| Organisation | National Institute of Allergy and Infectious Diseases (NIAID) |
| Sector | Public |
| Country | United States |
| Start | 11/2012 |
| End | 12/2014 |
| Description | King's College London Confidence in Concept 2018 |
| Amount | £1,000,000 (GBP) |
| Funding ID | MC_PC_18052 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2019 |
| End | 03/2021 |
| Description | MRC Centenary Early Career Award |
| Amount | £55,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2013 |
| End | 07/2013 |
| Description | MRC Transition Support CSF Alexandra Santos |
| Amount | £700,773 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2020 |
| End | 07/2022 |
| Description | NIAID - Immune Tolerance Network |
| Amount | £1,154,721 (GBP) |
| Organisation | National Institute of Allergy and Infectious Diseases (NIAID) |
| Sector | Public |
| Country | United States |
| Start | 02/2016 |
| End | 01/2019 |
| Description | National Institutes of Health (NIH) |
| Amount | £40,985 (GBP) |
| Organisation | National Institutes of Health (NIH) |
| Sector | Public |
| Country | United States |
| Start | 03/2021 |
| End | 12/2021 |
| Description | The Asthma UK Centre Allergy Mechanisms in Asthma |
| Amount | £953,495 (GBP) |
| Organisation | Asthma UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 07/2016 |
| End | 08/2021 |
| Description | Travel grant to attend the Annual Meeting of the British Society of Allergy and Clinical Immunology 2014 |
| Amount | £450 (GBP) |
| Organisation | British Society of Allergy and Clinical Immunology |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 05/2014 |
| End | 06/2014 |
| Title | Basophil activation test |
| Description | The whole blood basophil activation test is an in vitro assay where basophils in whole blood are stimulated with allergen and the expression of basophils' surface markers of activation are subsequently measured by flow cytometry. This assay was not previously performed in the host institution, was developed and optimised as part of the present research project and has proven to be very robust and to perform consistently. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2013 |
| Provided To Others? | Yes |
| Impact | The basophil activation test (BAT) will be assessed as a tool for the diagnosis of food allergy and will be used in mechanistic experiments. BAT will be clinically validated and may be applied in the diagnosis of food allergy in clinical practice, reducing the need for oral food challenges and inherent costs and risks. BAT will also be used to unravel immunologic mechanisms of allergy versus tolerance, allowing us to understand why some children with IgE to foods react clinically whilst other children with equivalent levels of IgE do not. |
| Title | Mast cell activation and inhibition assays |
| Description | The mast cell activation assay is a flow-cytomety based assay where mast cells from a cell line are sensitised with patients' plasma and stimulated with allergens or controls. It is an in vitro surrogate of provocation tests where patients are exposed to the allergens in vivo. The inhibition assay is similar, where the mast cells are in the presence of plasma samples that are tested for their ability to suppress mast cell activation. It can be used as a marker for clinical improvement of allergic disease. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | MAT can be used to diagnose food allergy and as a biomarker for clinical improvement in clinical trials testing preventive or therapeutic strategies for food allergy. |
| Title | LEAP Study Database |
| Description | The data collected as part of the LEAP Study has been made public as it is being published. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | Other researchers have been able to analyse the data themselves using Trialshare. |
| URL | https://www.itntrialshare.org/ |
| Title | Predicting Allergic Reactions During Oral Peanut Challenges |
| Description | his prediction tool calculates the reaction severity based on a published model developed from the LEAP, LEAP-On, and PAS studies. This tool uses the basophil activation test (BAT), skin prick test (SPT) size (mm), and the level of Ara h 2-specific IgE (kU/L) to predict reaction severity defined as no reaction, moderate reaction, or a severe reaction. The values of these biomarkers are combined to give the predicted probabilities of falling into each of the severity categories. This tool may be useful for clinicians when assessing the risk of conducting oral food challenges to diagnose peanut allergy. All study details and modeling are outlined in "Santos AF, et al., Biomarkers of severity and threshold of allergic reactions during oral peanut challenges. J Allergy Clin Immunol. 2020 Aug;146(2):344-355. PMID: 32311390." |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | This tool has been useful for clinical teams to determine the likelihood of patients to react during peanut challenges. |
| URL | https://benaroyaresearch.shinyapps.io/peanutallergytool/ |
| Description | Auto-anti-IgE project |
| Organisation | King's College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I contributed with intellectual input into the project regarding basophil experiments and also performed some experiments as part of this collaboration. |
| Collaborator Contribution | Professor Corrigan and his team recruited asthmatic and non-asthmatic subjects to the study and Professor Gould and her team performed experiments to detec the presence of anti-IgE and anti-FceRI and other auto antibodies in the serum of asthmatic and non-asthmatic subjects. |
| Impact | Publication PMID: 25112697 |
| Start Year | 2011 |
| Description | BAT to clinic |
| Organisation | Danaher Corporation |
| Department | Beckmann Coulter |
| Country | United States |
| Sector | Private |
| PI Contribution | We designed the study, the experiments, recruited the patients, generated and analysed the data and interpreted the results. We secured the fundings required to provide the necessary equipment and reagents for the project. |
| Collaborator Contribution | Viapath provided some time from their employees to support the project. Beckman Coulter provided the reagents for the trials runs before the start of the project. |
| Impact | Funding from the MRC Confidence in Concept Scheme through the KHP Challenge Fund. |
| Start Year | 2019 |
| Description | BAT to clinic |
| Organisation | Viapath |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | We designed the study, the experiments, recruited the patients, generated and analysed the data and interpreted the results. We secured the fundings required to provide the necessary equipment and reagents for the project. |
| Collaborator Contribution | Viapath provided some time from their employees to support the project. Beckman Coulter provided the reagents for the trials runs before the start of the project. |
| Impact | Funding from the MRC Confidence in Concept Scheme through the KHP Challenge Fund. |
| Start Year | 2019 |
| Description | Basophil activation test in the LEAP and LEAP-On studies |
| Organisation | National Institutes of Health (NIH) |
| Country | United States |
| Sector | Public |
| PI Contribution | Following successful development of basophil activation test to peanut, we have started to apply this technique to participants in the LEAP and LEAP-On studies. |
| Collaborator Contribution | The NIAID and the Immune Tolerance Network are funding and monitoring the LEAP and LEAP-On trials. |
| Impact | Publications are planned but for the time being we are still blinded for the |
| Start Year | 2011 |
| Description | Basophil activation test in the PRONUTS Study |
| Organisation | King's College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I have been performing the basophil activation test in participants in the Pronuts Study at the London site. |
| Collaborator Contribution | This is a multicentre study, including the 3 centres indicated above. All centres have been recruiting study participants. At KCL, I collaborate with Dr Helen Brough (PI) and Professor Gideon Lack (CI). |
| Impact | No outputs yet as the collaboration is ongoing and data will only be analysed at the end of the study. |
| Start Year | 2013 |
| Description | Basophil activation test in the PRONUTS Study |
| Organisation | University of Geneva |
| Country | Switzerland |
| Sector | Academic/University |
| PI Contribution | I have been performing the basophil activation test in participants in the Pronuts Study at the London site. |
| Collaborator Contribution | This is a multicentre study, including the 3 centres indicated above. All centres have been recruiting study participants. At KCL, I collaborate with Dr Helen Brough (PI) and Professor Gideon Lack (CI). |
| Impact | No outputs yet as the collaboration is ongoing and data will only be analysed at the end of the study. |
| Start Year | 2013 |
| Description | Basophil activation test in the PRONUTS Study |
| Organisation | University of Valencia |
| Country | Spain |
| Sector | Academic/University |
| PI Contribution | I have been performing the basophil activation test in participants in the Pronuts Study at the London site. |
| Collaborator Contribution | This is a multicentre study, including the 3 centres indicated above. All centres have been recruiting study participants. At KCL, I collaborate with Dr Helen Brough (PI) and Professor Gideon Lack (CI). |
| Impact | No outputs yet as the collaboration is ongoing and data will only be analysed at the end of the study. |
| Start Year | 2013 |
| Description | Basophil activation test in the TREAT study |
| Organisation | Murdoch Children's Research Institute |
| Country | Australia |
| Sector | Academic/University |
| PI Contribution | I have provided my expert advise and intellectual input in the design of experiments to assess basophil activation to tree nuts in children recruited into the Treeat Trial. |
| Collaborator Contribution | Treeat is an interventional randomised controlled study to find out if the introduction of multiple tree nuts in a hospital oral food challenge is better for prevention of tree nut allergy and is easier for families, than standard care. |
| Impact | None |
| Start Year | 2021 |
| Description | Basophil activation test to diagnose cow's milk allergy in Brazil |
| Organisation | Federal University of São Paulo |
| Country | Brazil |
| Sector | Academic/University |
| PI Contribution | I have provided expert advice on the study design and experimental set up of a study on the utility of the basophil activation test to diagnose cow's milk allergy in Sao Paulo. I have trained the PI of the study on the basophil activation test in my lab during a Sabbatical visit in 2020. |
| Collaborator Contribution | My collaborator is setting up and leading the study in Brazil. |
| Impact | Not yet. |
| Start Year | 2020 |
| Description | Epitope IgE and IgG4 testing |
| Organisation | Benaroya Research Institute |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | 1. We recruited patients who were being assessed for peanut allergy and designed the study in which we were assessing the hypothesis that differences in peanut epitope binding could explain differences in clinical reactivity (i.e. being allergic or not allergic) in children that had IgE to peanut. 2. We made contact with collaborators in New Orleans who tested IgE and IgG4 binding on a microarray containing peptides from all peanut allergens described to date. 3. We designed the analyses plan together with a computational biologist based in Oxford and Lisbon (now only in Lisbon) who performed the analyses of the microarray data. 4. We designed and performed functional assays to validate the findings using cellular tests in my laboratory. 5. We established a collaboration with Thermofisher to couple the peptides to a solid phase using ImmunoCAP technology, which enabled us to validate the microarray findings with quantitative method that could be come accessible to the clinical community. We tested all the samples in our laboratory using this technology. 6. ImmunoCAP and microarray data were analysed by statisticians at the BRI. |
| Collaborator Contribution | - Collaborators from Southern Regional Research Centre performed microarray experiments - Collaborators from University of Lisbon helped analysing the microarray data - Collaborators from Thermofisher scientific coupled the peptides to the solid phase using the peptides we provided and sent the material to our lab to use for testing. - Collaborators from Benaroya Research Institute analysed the ImmunoCAP data - Collaborators from Queen Mary University of London contributed in an advisory capacity |
| Impact | Abstract for meeting has been accepted as oral presentation to be presented at the annual congress of the European Academy of Allergy and Clinical Immunology. The manuscript is currently being reviewed by the editorial board of the Journal of Allergy and Clinical Immunology. |
| Start Year | 2011 |
| Description | Epitope IgE and IgG4 testing |
| Organisation | Queen Mary University of London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | 1. We recruited patients who were being assessed for peanut allergy and designed the study in which we were assessing the hypothesis that differences in peanut epitope binding could explain differences in clinical reactivity (i.e. being allergic or not allergic) in children that had IgE to peanut. 2. We made contact with collaborators in New Orleans who tested IgE and IgG4 binding on a microarray containing peptides from all peanut allergens described to date. 3. We designed the analyses plan together with a computational biologist based in Oxford and Lisbon (now only in Lisbon) who performed the analyses of the microarray data. 4. We designed and performed functional assays to validate the findings using cellular tests in my laboratory. 5. We established a collaboration with Thermofisher to couple the peptides to a solid phase using ImmunoCAP technology, which enabled us to validate the microarray findings with quantitative method that could be come accessible to the clinical community. We tested all the samples in our laboratory using this technology. 6. ImmunoCAP and microarray data were analysed by statisticians at the BRI. |
| Collaborator Contribution | - Collaborators from Southern Regional Research Centre performed microarray experiments - Collaborators from University of Lisbon helped analysing the microarray data - Collaborators from Thermofisher scientific coupled the peptides to the solid phase using the peptides we provided and sent the material to our lab to use for testing. - Collaborators from Benaroya Research Institute analysed the ImmunoCAP data - Collaborators from Queen Mary University of London contributed in an advisory capacity |
| Impact | Abstract for meeting has been accepted as oral presentation to be presented at the annual congress of the European Academy of Allergy and Clinical Immunology. The manuscript is currently being reviewed by the editorial board of the Journal of Allergy and Clinical Immunology. |
| Start Year | 2011 |
| Description | Epitope IgE and IgG4 testing |
| Organisation | Thermo Fisher Scientific |
| Country | United States |
| Sector | Private |
| PI Contribution | 1. We recruited patients who were being assessed for peanut allergy and designed the study in which we were assessing the hypothesis that differences in peanut epitope binding could explain differences in clinical reactivity (i.e. being allergic or not allergic) in children that had IgE to peanut. 2. We made contact with collaborators in New Orleans who tested IgE and IgG4 binding on a microarray containing peptides from all peanut allergens described to date. 3. We designed the analyses plan together with a computational biologist based in Oxford and Lisbon (now only in Lisbon) who performed the analyses of the microarray data. 4. We designed and performed functional assays to validate the findings using cellular tests in my laboratory. 5. We established a collaboration with Thermofisher to couple the peptides to a solid phase using ImmunoCAP technology, which enabled us to validate the microarray findings with quantitative method that could be come accessible to the clinical community. We tested all the samples in our laboratory using this technology. 6. ImmunoCAP and microarray data were analysed by statisticians at the BRI. |
| Collaborator Contribution | - Collaborators from Southern Regional Research Centre performed microarray experiments - Collaborators from University of Lisbon helped analysing the microarray data - Collaborators from Thermofisher scientific coupled the peptides to the solid phase using the peptides we provided and sent the material to our lab to use for testing. - Collaborators from Benaroya Research Institute analysed the ImmunoCAP data - Collaborators from Queen Mary University of London contributed in an advisory capacity |
| Impact | Abstract for meeting has been accepted as oral presentation to be presented at the annual congress of the European Academy of Allergy and Clinical Immunology. The manuscript is currently being reviewed by the editorial board of the Journal of Allergy and Clinical Immunology. |
| Start Year | 2011 |
| Description | Epitope IgE and IgG4 testing |
| Organisation | U.S. Department of Agriculture USDA |
| Department | Agricultural Research Service |
| Country | United States |
| Sector | Public |
| PI Contribution | 1. We recruited patients who were being assessed for peanut allergy and designed the study in which we were assessing the hypothesis that differences in peanut epitope binding could explain differences in clinical reactivity (i.e. being allergic or not allergic) in children that had IgE to peanut. 2. We made contact with collaborators in New Orleans who tested IgE and IgG4 binding on a microarray containing peptides from all peanut allergens described to date. 3. We designed the analyses plan together with a computational biologist based in Oxford and Lisbon (now only in Lisbon) who performed the analyses of the microarray data. 4. We designed and performed functional assays to validate the findings using cellular tests in my laboratory. 5. We established a collaboration with Thermofisher to couple the peptides to a solid phase using ImmunoCAP technology, which enabled us to validate the microarray findings with quantitative method that could be come accessible to the clinical community. We tested all the samples in our laboratory using this technology. 6. ImmunoCAP and microarray data were analysed by statisticians at the BRI. |
| Collaborator Contribution | - Collaborators from Southern Regional Research Centre performed microarray experiments - Collaborators from University of Lisbon helped analysing the microarray data - Collaborators from Thermofisher scientific coupled the peptides to the solid phase using the peptides we provided and sent the material to our lab to use for testing. - Collaborators from Benaroya Research Institute analysed the ImmunoCAP data - Collaborators from Queen Mary University of London contributed in an advisory capacity |
| Impact | Abstract for meeting has been accepted as oral presentation to be presented at the annual congress of the European Academy of Allergy and Clinical Immunology. The manuscript is currently being reviewed by the editorial board of the Journal of Allergy and Clinical Immunology. |
| Start Year | 2011 |
| Description | Epitope IgE and IgG4 testing |
| Organisation | University of Lisbon |
| Department | Institute for Molecular Medicine |
| Country | Portugal |
| Sector | Academic/University |
| PI Contribution | 1. We recruited patients who were being assessed for peanut allergy and designed the study in which we were assessing the hypothesis that differences in peanut epitope binding could explain differences in clinical reactivity (i.e. being allergic or not allergic) in children that had IgE to peanut. 2. We made contact with collaborators in New Orleans who tested IgE and IgG4 binding on a microarray containing peptides from all peanut allergens described to date. 3. We designed the analyses plan together with a computational biologist based in Oxford and Lisbon (now only in Lisbon) who performed the analyses of the microarray data. 4. We designed and performed functional assays to validate the findings using cellular tests in my laboratory. 5. We established a collaboration with Thermofisher to couple the peptides to a solid phase using ImmunoCAP technology, which enabled us to validate the microarray findings with quantitative method that could be come accessible to the clinical community. We tested all the samples in our laboratory using this technology. 6. ImmunoCAP and microarray data were analysed by statisticians at the BRI. |
| Collaborator Contribution | - Collaborators from Southern Regional Research Centre performed microarray experiments - Collaborators from University of Lisbon helped analysing the microarray data - Collaborators from Thermofisher scientific coupled the peptides to the solid phase using the peptides we provided and sent the material to our lab to use for testing. - Collaborators from Benaroya Research Institute analysed the ImmunoCAP data - Collaborators from Queen Mary University of London contributed in an advisory capacity |
| Impact | Abstract for meeting has been accepted as oral presentation to be presented at the annual congress of the European Academy of Allergy and Clinical Immunology. The manuscript is currently being reviewed by the editorial board of the Journal of Allergy and Clinical Immunology. |
| Start Year | 2011 |
| Description | Epitope IgE testing |
| Organisation | Thermo Fisher Scientific |
| Country | United States |
| Sector | Private |
| PI Contribution | We identified key epitope-containing peptides in peanut allergens and provided the peptides to our collaborator, who couple them to a solid phase using the ImmunoCAP technology to enable us to measure IgE and IgG4 to the peptides. With this, we validated our findings and found a clinical application given that these peptides had diagnostic value. |
| Collaborator Contribution | Our collaborator couple the peptides of interest to a solid phase using the ImmunoCAP technology. |
| Impact | Examples of outputs that resulted from this collaboration were posters and oral abstracts presented at internal and extrenal conferences and one peer-reviewed publication. More are in preparation. |
| Start Year | 2018 |
| Description | Epitope IgE testing |
| Organisation | Thermofisher - Uppsala |
| Country | Sweden |
| Sector | Private |
| PI Contribution | We identified key epitope-containing peptides in peanut allergens and provided the peptides to our collaborator, who couple them to a solid phase using the ImmunoCAP technology to enable us to measure IgE and IgG4 to the peptides. With this, we validated our findings and found a clinical application given that these peptides had diagnostic value. |
| Collaborator Contribution | Our collaborator couple the peptides of interest to a solid phase using the ImmunoCAP technology. |
| Impact | Examples of outputs that resulted from this collaboration were posters and oral abstracts presented at internal and extrenal conferences and one peer-reviewed publication. More are in preparation. |
| Start Year | 2018 |
| Description | Mast cell activation test as biomarker of resolution of food allergy |
| Organisation | King's College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | My lab has provided training of a PhD student on the mast cell activation and has provided the equipment and reagents to enable this test. |
| Collaborator Contribution | The EAT study team is providing plasma samples to be tested on the mast cell activation test. |
| Impact | No outputs yet. |
| Start Year | 2018 |
| Description | Modification of antibody function with early peanut consumption |
| Organisation | Immune Tolerance Network |
| Country | United States |
| Sector | Charity/Non Profit |
| PI Contribution | My research team will be testing samples of participants in the LEAP, LEAP-On and PAS studies on the mast cell activation test. |
| Collaborator Contribution | ITN will be sending plasma samples from participants in the LEAP, LEAP-On and PAS studies alongside with funding to support the experimental work. |
| Impact | No outputs yet. |
| Start Year | 2020 |
| Description | Natural history of food allergy in the EAT cohort |
| Organisation | King's College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I have provided my expertie in antibody responses and mast cell activation to allergens in food allergy and spontaneous resolution of food allergy. I have supervised a KCL Clinical PhD student doing experimental work testing samples from the EAT study over time. This is a study funded by the MRC and Action Medical Research. I have provided intellectual input, training of the PhD student and access to equipment and facilities. |
| Collaborator Contribution | The collaborators have provided clinical information about the study participants. |
| Impact | Foong RX, Santos AF*. Biomarkers of diagnosis and resolution of food allergy. Pediatr Allergy Immunol 2021; 32: 223-233. *Corresponding author |
| Start Year | 2019 |
| Description | Preventing peanut allergy through improved understanding of the transcutaneous sensitisation route, novel food processing and skin care adaptations (TRANS-FOODS) |
| Organisation | Charité - University of Medicine Berlin |
| Department | Paediatric Endocrinology Charité |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | As part of this consortium, I provide expertise on food allergy and risk factors for sensitisation and allergic reactions and also about peanut allergens, their allergenicity and effect of their modification. In my laboratory at King's College London, my team will test the samples of interstitial fluid retrieved from the skin of adults participating in the clinical study planned as part of WP4 to assess the ability of peanut proteins contained in the interstitial skin fluid to interact with immune cells. Specifically, I plan is to use these samples to stimulate basophils in whole blood collected from peanut allergic donors, alongside the relevant controls, and assess basophil activation by flow cytometry. The basophil activation assay to peanut is well established in my laboratory. I have previously shown that it has 97% accuracy with 98% sensitivity and 96% specificity to diagnose peanut allergy with basophil activation being detectable below 1ng/ml of peanut protein. The basophil activation test is therefore a very sensitive and specific method to detect the presence and the allergenicity of peanut proteins. The basophil activation test can be very informative to demonstrate retained allergenicity and immunogenicity of peanut proteins that have crossed the skin barrier in adults, with or without atopic eczema, who have applied different peanut-containing preparations on to the skin. The evidence that sensitisation to food allergens can occur through the skin and the demonstration of the mechanisms by which this happens can potentially identify ways to reduce allergen exposure and to prevent the development of peanut and other food allergies in infants and children and possibly later in the life course. |
| Collaborator Contribution | Background: Allergic diseases, including atopic dermatitis (AD) and food allergies (FA), affect over a quarter of all children across Europe. The immune responses to oral food allergens are well-established and controlled oral allergen exposure methods in early life have been developed that can prevent FA. However, it is not easy to comply with the repeated oral allergen exposure required to induce tolerance and additional approaches are therefore needed. There is mounting evidence that early life cutaneous exposure to foods causes sensitisation, especially in the presence of dry skin and AD. Despite this, very little is known about how the cutaneous sensitisation to FA occurs. Aims: This project aims to reduce the risk of peanut allergy development through the transcutaneous route by 1) understanding the mechanisms through which this occurs, and 2) designing and testing novel prevention approaches, such as modification in the peanut manufacturing processes and the adaptation of skin care practices. Workplan: These ambitious, but achievable aims are addressed in integrated workpackages, taken forward by leaders in their respective fields from the UK, Germany, and France: WP1 addresses the effects of food processing upon the solubility of peanut protein and its components in oil and how this relates to the cutaneous exposure to peanut protein. WP2 examines the effect of peanut protein skin contamination and skin appendage trapping. WP3 studies the immune system activation induced by massage and cutaneous peanut exposure. WP4 uses an intervention study approach with skin massage to study the immune responses to peanut allergen in those with a skin barrier defect. WP5 examines the cutaneous immune responses to peanut allergen in those suffering of peanut allergy, and, WP6 translates our findings through working with an industrial peanut processing partner, patients and consumers. Impact of expected results: We will work with the food industry, Allergy UK, the Natasha Allergy Research Foundation, as well as national and international food standards agencies to ensure stakeholder awareness and that the findings of our work are translated into improved public health measures. |
| Impact | Not yet |
| Start Year | 2021 |
| Description | Preventing peanut allergy through improved understanding of the transcutaneous sensitisation route, novel food processing and skin care adaptations (TRANS-FOODS) |
| Organisation | Curie Institute Paris (Institut Curie) |
| Department | BioPhenics Platform |
| Country | France |
| Sector | Public |
| PI Contribution | As part of this consortium, I provide expertise on food allergy and risk factors for sensitisation and allergic reactions and also about peanut allergens, their allergenicity and effect of their modification. In my laboratory at King's College London, my team will test the samples of interstitial fluid retrieved from the skin of adults participating in the clinical study planned as part of WP4 to assess the ability of peanut proteins contained in the interstitial skin fluid to interact with immune cells. Specifically, I plan is to use these samples to stimulate basophils in whole blood collected from peanut allergic donors, alongside the relevant controls, and assess basophil activation by flow cytometry. The basophil activation assay to peanut is well established in my laboratory. I have previously shown that it has 97% accuracy with 98% sensitivity and 96% specificity to diagnose peanut allergy with basophil activation being detectable below 1ng/ml of peanut protein. The basophil activation test is therefore a very sensitive and specific method to detect the presence and the allergenicity of peanut proteins. The basophil activation test can be very informative to demonstrate retained allergenicity and immunogenicity of peanut proteins that have crossed the skin barrier in adults, with or without atopic eczema, who have applied different peanut-containing preparations on to the skin. The evidence that sensitisation to food allergens can occur through the skin and the demonstration of the mechanisms by which this happens can potentially identify ways to reduce allergen exposure and to prevent the development of peanut and other food allergies in infants and children and possibly later in the life course. |
| Collaborator Contribution | Background: Allergic diseases, including atopic dermatitis (AD) and food allergies (FA), affect over a quarter of all children across Europe. The immune responses to oral food allergens are well-established and controlled oral allergen exposure methods in early life have been developed that can prevent FA. However, it is not easy to comply with the repeated oral allergen exposure required to induce tolerance and additional approaches are therefore needed. There is mounting evidence that early life cutaneous exposure to foods causes sensitisation, especially in the presence of dry skin and AD. Despite this, very little is known about how the cutaneous sensitisation to FA occurs. Aims: This project aims to reduce the risk of peanut allergy development through the transcutaneous route by 1) understanding the mechanisms through which this occurs, and 2) designing and testing novel prevention approaches, such as modification in the peanut manufacturing processes and the adaptation of skin care practices. Workplan: These ambitious, but achievable aims are addressed in integrated workpackages, taken forward by leaders in their respective fields from the UK, Germany, and France: WP1 addresses the effects of food processing upon the solubility of peanut protein and its components in oil and how this relates to the cutaneous exposure to peanut protein. WP2 examines the effect of peanut protein skin contamination and skin appendage trapping. WP3 studies the immune system activation induced by massage and cutaneous peanut exposure. WP4 uses an intervention study approach with skin massage to study the immune responses to peanut allergen in those with a skin barrier defect. WP5 examines the cutaneous immune responses to peanut allergen in those suffering of peanut allergy, and, WP6 translates our findings through working with an industrial peanut processing partner, patients and consumers. Impact of expected results: We will work with the food industry, Allergy UK, the Natasha Allergy Research Foundation, as well as national and international food standards agencies to ensure stakeholder awareness and that the findings of our work are translated into improved public health measures. |
| Impact | Not yet |
| Start Year | 2021 |
| Description | Preventing peanut allergy through improved understanding of the transcutaneous sensitisation route, novel food processing and skin care adaptations (TRANS-FOODS) |
| Organisation | King's College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | As part of this consortium, I provide expertise on food allergy and risk factors for sensitisation and allergic reactions and also about peanut allergens, their allergenicity and effect of their modification. In my laboratory at King's College London, my team will test the samples of interstitial fluid retrieved from the skin of adults participating in the clinical study planned as part of WP4 to assess the ability of peanut proteins contained in the interstitial skin fluid to interact with immune cells. Specifically, I plan is to use these samples to stimulate basophils in whole blood collected from peanut allergic donors, alongside the relevant controls, and assess basophil activation by flow cytometry. The basophil activation assay to peanut is well established in my laboratory. I have previously shown that it has 97% accuracy with 98% sensitivity and 96% specificity to diagnose peanut allergy with basophil activation being detectable below 1ng/ml of peanut protein. The basophil activation test is therefore a very sensitive and specific method to detect the presence and the allergenicity of peanut proteins. The basophil activation test can be very informative to demonstrate retained allergenicity and immunogenicity of peanut proteins that have crossed the skin barrier in adults, with or without atopic eczema, who have applied different peanut-containing preparations on to the skin. The evidence that sensitisation to food allergens can occur through the skin and the demonstration of the mechanisms by which this happens can potentially identify ways to reduce allergen exposure and to prevent the development of peanut and other food allergies in infants and children and possibly later in the life course. |
| Collaborator Contribution | Background: Allergic diseases, including atopic dermatitis (AD) and food allergies (FA), affect over a quarter of all children across Europe. The immune responses to oral food allergens are well-established and controlled oral allergen exposure methods in early life have been developed that can prevent FA. However, it is not easy to comply with the repeated oral allergen exposure required to induce tolerance and additional approaches are therefore needed. There is mounting evidence that early life cutaneous exposure to foods causes sensitisation, especially in the presence of dry skin and AD. Despite this, very little is known about how the cutaneous sensitisation to FA occurs. Aims: This project aims to reduce the risk of peanut allergy development through the transcutaneous route by 1) understanding the mechanisms through which this occurs, and 2) designing and testing novel prevention approaches, such as modification in the peanut manufacturing processes and the adaptation of skin care practices. Workplan: These ambitious, but achievable aims are addressed in integrated workpackages, taken forward by leaders in their respective fields from the UK, Germany, and France: WP1 addresses the effects of food processing upon the solubility of peanut protein and its components in oil and how this relates to the cutaneous exposure to peanut protein. WP2 examines the effect of peanut protein skin contamination and skin appendage trapping. WP3 studies the immune system activation induced by massage and cutaneous peanut exposure. WP4 uses an intervention study approach with skin massage to study the immune responses to peanut allergen in those with a skin barrier defect. WP5 examines the cutaneous immune responses to peanut allergen in those suffering of peanut allergy, and, WP6 translates our findings through working with an industrial peanut processing partner, patients and consumers. Impact of expected results: We will work with the food industry, Allergy UK, the Natasha Allergy Research Foundation, as well as national and international food standards agencies to ensure stakeholder awareness and that the findings of our work are translated into improved public health measures. |
| Impact | Not yet |
| Start Year | 2021 |
| Description | Preventing peanut allergy through improved understanding of the transcutaneous sensitisation route, novel food processing and skin care adaptations (TRANS-FOODS) |
| Organisation | University of Bonn |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | As part of this consortium, I provide expertise on food allergy and risk factors for sensitisation and allergic reactions and also about peanut allergens, their allergenicity and effect of their modification. In my laboratory at King's College London, my team will test the samples of interstitial fluid retrieved from the skin of adults participating in the clinical study planned as part of WP4 to assess the ability of peanut proteins contained in the interstitial skin fluid to interact with immune cells. Specifically, I plan is to use these samples to stimulate basophils in whole blood collected from peanut allergic donors, alongside the relevant controls, and assess basophil activation by flow cytometry. The basophil activation assay to peanut is well established in my laboratory. I have previously shown that it has 97% accuracy with 98% sensitivity and 96% specificity to diagnose peanut allergy with basophil activation being detectable below 1ng/ml of peanut protein. The basophil activation test is therefore a very sensitive and specific method to detect the presence and the allergenicity of peanut proteins. The basophil activation test can be very informative to demonstrate retained allergenicity and immunogenicity of peanut proteins that have crossed the skin barrier in adults, with or without atopic eczema, who have applied different peanut-containing preparations on to the skin. The evidence that sensitisation to food allergens can occur through the skin and the demonstration of the mechanisms by which this happens can potentially identify ways to reduce allergen exposure and to prevent the development of peanut and other food allergies in infants and children and possibly later in the life course. |
| Collaborator Contribution | Background: Allergic diseases, including atopic dermatitis (AD) and food allergies (FA), affect over a quarter of all children across Europe. The immune responses to oral food allergens are well-established and controlled oral allergen exposure methods in early life have been developed that can prevent FA. However, it is not easy to comply with the repeated oral allergen exposure required to induce tolerance and additional approaches are therefore needed. There is mounting evidence that early life cutaneous exposure to foods causes sensitisation, especially in the presence of dry skin and AD. Despite this, very little is known about how the cutaneous sensitisation to FA occurs. Aims: This project aims to reduce the risk of peanut allergy development through the transcutaneous route by 1) understanding the mechanisms through which this occurs, and 2) designing and testing novel prevention approaches, such as modification in the peanut manufacturing processes and the adaptation of skin care practices. Workplan: These ambitious, but achievable aims are addressed in integrated workpackages, taken forward by leaders in their respective fields from the UK, Germany, and France: WP1 addresses the effects of food processing upon the solubility of peanut protein and its components in oil and how this relates to the cutaneous exposure to peanut protein. WP2 examines the effect of peanut protein skin contamination and skin appendage trapping. WP3 studies the immune system activation induced by massage and cutaneous peanut exposure. WP4 uses an intervention study approach with skin massage to study the immune responses to peanut allergen in those with a skin barrier defect. WP5 examines the cutaneous immune responses to peanut allergen in those suffering of peanut allergy, and, WP6 translates our findings through working with an industrial peanut processing partner, patients and consumers. Impact of expected results: We will work with the food industry, Allergy UK, the Natasha Allergy Research Foundation, as well as national and international food standards agencies to ensure stakeholder awareness and that the findings of our work are translated into improved public health measures. |
| Impact | Not yet |
| Start Year | 2021 |
| Description | STOPPING ECZEMA AND ALLERGY (SEAL) STUDY: PREVENT THE ALLERGIC MARCH BY ENHANCING THE SKIN BARRIER |
| Organisation | Benaroya Research Institute |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | I have contributed to this collaboration with my expertise on basophil and mast cell responses to food allergens in high risk children and using in vitro assays. My team in my laboratory will be testing samples from children recruited into the Seal study on the mast cell activation test that I have established in my lab. |
| Collaborator Contribution | Stanford, Chicago, Denver and London will be the clinical sites recruiting patients for the Seal Study. Immune mechanistic work will also be undertaken at the sites, namely: skin barrier (Denver), microbiome (Chicago), T cells (Stanford) and mast cells (London). |
| Impact | Brough HA, Lanser BJ, Sindher SB, Teng JMC, Leung DYM, Venter C, Chan SM, Santos AF, Bahnson HT, Guttman-Yassky E, Gupta RS, Lack G, Ciaccio CE, Sampath V, Nadeau KC, Nagler CR. Early intervention and prevention of allergic diseases. Allergy 2021; doi: 10.1111/all.15006. |
| Start Year | 2020 |
| Description | STOPPING ECZEMA AND ALLERGY (SEAL) STUDY: PREVENT THE ALLERGIC MARCH BY ENHANCING THE SKIN BARRIER |
| Organisation | National Jewish Medical and Research Center, USA |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | I have contributed to this collaboration with my expertise on basophil and mast cell responses to food allergens in high risk children and using in vitro assays. My team in my laboratory will be testing samples from children recruited into the Seal study on the mast cell activation test that I have established in my lab. |
| Collaborator Contribution | Stanford, Chicago, Denver and London will be the clinical sites recruiting patients for the Seal Study. Immune mechanistic work will also be undertaken at the sites, namely: skin barrier (Denver), microbiome (Chicago), T cells (Stanford) and mast cells (London). |
| Impact | Brough HA, Lanser BJ, Sindher SB, Teng JMC, Leung DYM, Venter C, Chan SM, Santos AF, Bahnson HT, Guttman-Yassky E, Gupta RS, Lack G, Ciaccio CE, Sampath V, Nadeau KC, Nagler CR. Early intervention and prevention of allergic diseases. Allergy 2021; doi: 10.1111/all.15006. |
| Start Year | 2020 |
| Description | STOPPING ECZEMA AND ALLERGY (SEAL) STUDY: PREVENT THE ALLERGIC MARCH BY ENHANCING THE SKIN BARRIER |
| Organisation | Stanford University |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | I have contributed to this collaboration with my expertise on basophil and mast cell responses to food allergens in high risk children and using in vitro assays. My team in my laboratory will be testing samples from children recruited into the Seal study on the mast cell activation test that I have established in my lab. |
| Collaborator Contribution | Stanford, Chicago, Denver and London will be the clinical sites recruiting patients for the Seal Study. Immune mechanistic work will also be undertaken at the sites, namely: skin barrier (Denver), microbiome (Chicago), T cells (Stanford) and mast cells (London). |
| Impact | Brough HA, Lanser BJ, Sindher SB, Teng JMC, Leung DYM, Venter C, Chan SM, Santos AF, Bahnson HT, Guttman-Yassky E, Gupta RS, Lack G, Ciaccio CE, Sampath V, Nadeau KC, Nagler CR. Early intervention and prevention of allergic diseases. Allergy 2021; doi: 10.1111/all.15006. |
| Start Year | 2020 |
| Description | STOPPING ECZEMA AND ALLERGY (SEAL) STUDY: PREVENT THE ALLERGIC MARCH BY ENHANCING THE SKIN BARRIER |
| Organisation | University of Chicago |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | I have contributed to this collaboration with my expertise on basophil and mast cell responses to food allergens in high risk children and using in vitro assays. My team in my laboratory will be testing samples from children recruited into the Seal study on the mast cell activation test that I have established in my lab. |
| Collaborator Contribution | Stanford, Chicago, Denver and London will be the clinical sites recruiting patients for the Seal Study. Immune mechanistic work will also be undertaken at the sites, namely: skin barrier (Denver), microbiome (Chicago), T cells (Stanford) and mast cells (London). |
| Impact | Brough HA, Lanser BJ, Sindher SB, Teng JMC, Leung DYM, Venter C, Chan SM, Santos AF, Bahnson HT, Guttman-Yassky E, Gupta RS, Lack G, Ciaccio CE, Sampath V, Nadeau KC, Nagler CR. Early intervention and prevention of allergic diseases. Allergy 2021; doi: 10.1111/all.15006. |
| Start Year | 2020 |
| Description | Task-force for the external quality assurance of the basophil activation test |
| Organisation | Aarhus University |
| Country | Denmark |
| Sector | Academic/University |
| PI Contribution | I have planned the task force and contributed with ideas for the best way forward in the standardisation and quality assurance of the basophil activation test across different centres in Europe. Me and my team have also tested samples that were sent around the various laboratories and provided the results to the group. I have critically analysed the results and interpreted them as we are preparing the manuscript for submission. |
| Collaborator Contribution | The partners in this collaboration have provided data and input from their own centres. |
| Impact | We are now preparing a manuscript for publication and setting up a system with a central european laboratory for quality assurance of the BAT. |
| Start Year | 2017 |
| Description | Task-force for the external quality assurance of the basophil activation test |
| Organisation | Antwerp University Hospital |
| Country | Belgium |
| Sector | Hospitals |
| PI Contribution | I have planned the task force and contributed with ideas for the best way forward in the standardisation and quality assurance of the basophil activation test across different centres in Europe. Me and my team have also tested samples that were sent around the various laboratories and provided the results to the group. I have critically analysed the results and interpreted them as we are preparing the manuscript for submission. |
| Collaborator Contribution | The partners in this collaboration have provided data and input from their own centres. |
| Impact | We are now preparing a manuscript for publication and setting up a system with a central european laboratory for quality assurance of the BAT. |
| Start Year | 2017 |
| Description | Task-force for the external quality assurance of the basophil activation test |
| Organisation | August Pi i Sunyer Biomedical Research Institute |
| Department | Hospital Clinic of Barcelona |
| Country | Spain |
| Sector | Hospitals |
| PI Contribution | I have planned the task force and contributed with ideas for the best way forward in the standardisation and quality assurance of the basophil activation test across different centres in Europe. Me and my team have also tested samples that were sent around the various laboratories and provided the results to the group. I have critically analysed the results and interpreted them as we are preparing the manuscript for submission. |
| Collaborator Contribution | The partners in this collaboration have provided data and input from their own centres. |
| Impact | We are now preparing a manuscript for publication and setting up a system with a central european laboratory for quality assurance of the BAT. |
| Start Year | 2017 |
| Description | Task-force for the external quality assurance of the basophil activation test |
| Organisation | Imperial College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I have planned the task force and contributed with ideas for the best way forward in the standardisation and quality assurance of the basophil activation test across different centres in Europe. Me and my team have also tested samples that were sent around the various laboratories and provided the results to the group. I have critically analysed the results and interpreted them as we are preparing the manuscript for submission. |
| Collaborator Contribution | The partners in this collaboration have provided data and input from their own centres. |
| Impact | We are now preparing a manuscript for publication and setting up a system with a central european laboratory for quality assurance of the BAT. |
| Start Year | 2017 |
| Description | Task-force for the external quality assurance of the basophil activation test |
| Organisation | Karolinska Institute |
| Country | Sweden |
| Sector | Academic/University |
| PI Contribution | I have planned the task force and contributed with ideas for the best way forward in the standardisation and quality assurance of the basophil activation test across different centres in Europe. Me and my team have also tested samples that were sent around the various laboratories and provided the results to the group. I have critically analysed the results and interpreted them as we are preparing the manuscript for submission. |
| Collaborator Contribution | The partners in this collaboration have provided data and input from their own centres. |
| Impact | We are now preparing a manuscript for publication and setting up a system with a central european laboratory for quality assurance of the BAT. |
| Start Year | 2017 |
| Description | Task-force for the external quality assurance of the basophil activation test |
| Organisation | Technical University of Munich |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | I have planned the task force and contributed with ideas for the best way forward in the standardisation and quality assurance of the basophil activation test across different centres in Europe. Me and my team have also tested samples that were sent around the various laboratories and provided the results to the group. I have critically analysed the results and interpreted them as we are preparing the manuscript for submission. |
| Collaborator Contribution | The partners in this collaboration have provided data and input from their own centres. |
| Impact | We are now preparing a manuscript for publication and setting up a system with a central european laboratory for quality assurance of the BAT. |
| Start Year | 2017 |
| Description | Task-force for the external quality assurance of the basophil activation test |
| Organisation | University of Bonn |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | I have planned the task force and contributed with ideas for the best way forward in the standardisation and quality assurance of the basophil activation test across different centres in Europe. Me and my team have also tested samples that were sent around the various laboratories and provided the results to the group. I have critically analysed the results and interpreted them as we are preparing the manuscript for submission. |
| Collaborator Contribution | The partners in this collaboration have provided data and input from their own centres. |
| Impact | We are now preparing a manuscript for publication and setting up a system with a central european laboratory for quality assurance of the BAT. |
| Start Year | 2017 |
| Description | Task-force for the external quality assurance of the basophil activation test |
| Organisation | University of Helsinki |
| Country | Finland |
| Sector | Academic/University |
| PI Contribution | I have planned the task force and contributed with ideas for the best way forward in the standardisation and quality assurance of the basophil activation test across different centres in Europe. Me and my team have also tested samples that were sent around the various laboratories and provided the results to the group. I have critically analysed the results and interpreted them as we are preparing the manuscript for submission. |
| Collaborator Contribution | The partners in this collaboration have provided data and input from their own centres. |
| Impact | We are now preparing a manuscript for publication and setting up a system with a central european laboratory for quality assurance of the BAT. |
| Start Year | 2017 |
| Description | Task-force for the external quality assurance of the basophil activation test |
| Organisation | University of Malaga |
| Country | Spain |
| Sector | Academic/University |
| PI Contribution | I have planned the task force and contributed with ideas for the best way forward in the standardisation and quality assurance of the basophil activation test across different centres in Europe. Me and my team have also tested samples that were sent around the various laboratories and provided the results to the group. I have critically analysed the results and interpreted them as we are preparing the manuscript for submission. |
| Collaborator Contribution | The partners in this collaboration have provided data and input from their own centres. |
| Impact | We are now preparing a manuscript for publication and setting up a system with a central european laboratory for quality assurance of the BAT. |
| Start Year | 2017 |
| Description | Task-force for the external quality assurance of the basophil activation test |
| Organisation | Utrecht University |
| Country | Netherlands |
| Sector | Academic/University |
| PI Contribution | I have planned the task force and contributed with ideas for the best way forward in the standardisation and quality assurance of the basophil activation test across different centres in Europe. Me and my team have also tested samples that were sent around the various laboratories and provided the results to the group. I have critically analysed the results and interpreted them as we are preparing the manuscript for submission. |
| Collaborator Contribution | The partners in this collaboration have provided data and input from their own centres. |
| Impact | We are now preparing a manuscript for publication and setting up a system with a central european laboratory for quality assurance of the BAT. |
| Start Year | 2017 |
| Description | UK Multicentre biomarker-led randomised-controlled trial of the basophil and mast cell activation tests in food allergy |
| Organisation | Addenbrooke's Hospital |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | We have designed the study and will be distributing electronic clinical questionnaires as well as centralising the blood samples to perform the basophil and mast cell activation studies to the various allergens. |
| Collaborator Contribution | The various partners will be consenting participants and send their anonymised clinical information as well as blood samples to KCL. |
| Impact | No outputs yet. |
| Start Year | 2020 |
| Description | UK Multicentre biomarker-led randomised-controlled trial of the basophil and mast cell activation tests in food allergy |
| Organisation | King's College Hospital |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | We have designed the study and will be distributing electronic clinical questionnaires as well as centralising the blood samples to perform the basophil and mast cell activation studies to the various allergens. |
| Collaborator Contribution | The various partners will be consenting participants and send their anonymised clinical information as well as blood samples to KCL. |
| Impact | No outputs yet. |
| Start Year | 2020 |
| Description | UK Multicentre biomarker-led randomised-controlled trial of the basophil and mast cell activation tests in food allergy |
| Organisation | King's College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have designed the study and will be distributing electronic clinical questionnaires as well as centralising the blood samples to perform the basophil and mast cell activation studies to the various allergens. |
| Collaborator Contribution | The various partners will be consenting participants and send their anonymised clinical information as well as blood samples to KCL. |
| Impact | No outputs yet. |
| Start Year | 2020 |
| Description | UK Multicentre biomarker-led randomised-controlled trial of the basophil and mast cell activation tests in food allergy |
| Organisation | Newcastle upon Tyne Hospitals NHS Foundation Trust |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have designed the study and will be distributing electronic clinical questionnaires as well as centralising the blood samples to perform the basophil and mast cell activation studies to the various allergens. |
| Collaborator Contribution | The various partners will be consenting participants and send their anonymised clinical information as well as blood samples to KCL. |
| Impact | No outputs yet. |
| Start Year | 2020 |
| Description | UK Multicentre biomarker-led randomised-controlled trial of the basophil and mast cell activation tests in food allergy |
| Organisation | Royal Manchester Children's Hospital |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | We have designed the study and will be distributing electronic clinical questionnaires as well as centralising the blood samples to perform the basophil and mast cell activation studies to the various allergens. |
| Collaborator Contribution | The various partners will be consenting participants and send their anonymised clinical information as well as blood samples to KCL. |
| Impact | No outputs yet. |
| Start Year | 2020 |
| Description | UK Multicentre biomarker-led randomised-controlled trial of the basophil and mast cell activation tests in food allergy |
| Organisation | Sandwell and West Birmingham Hospitals NHS Trust |
| Department | Rheumatology Sandwell and West Birmingham |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | We have designed the study and will be distributing electronic clinical questionnaires as well as centralising the blood samples to perform the basophil and mast cell activation studies to the various allergens. |
| Collaborator Contribution | The various partners will be consenting participants and send their anonymised clinical information as well as blood samples to KCL. |
| Impact | No outputs yet. |
| Start Year | 2020 |
| Description | UK Multicentre biomarker-led randomised-controlled trial of the basophil and mast cell activation tests in food allergy |
| Organisation | Sheffield Children's Hospital |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | We have designed the study and will be distributing electronic clinical questionnaires as well as centralising the blood samples to perform the basophil and mast cell activation studies to the various allergens. |
| Collaborator Contribution | The various partners will be consenting participants and send their anonymised clinical information as well as blood samples to KCL. |
| Impact | No outputs yet. |
| Start Year | 2020 |
| Description | UK Multicentre biomarker-led randomised-controlled trial of the basophil and mast cell activation tests in food allergy |
| Organisation | Southampton Hospital |
| Country | United States |
| Sector | Hospitals |
| PI Contribution | We have designed the study and will be distributing electronic clinical questionnaires as well as centralising the blood samples to perform the basophil and mast cell activation studies to the various allergens. |
| Collaborator Contribution | The various partners will be consenting participants and send their anonymised clinical information as well as blood samples to KCL. |
| Impact | No outputs yet. |
| Start Year | 2020 |
| Description | UK Multicentre biomarker-led randomised-controlled trial of the basophil and mast cell activation tests in food allergy |
| Organisation | University College Hospital |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | We have designed the study and will be distributing electronic clinical questionnaires as well as centralising the blood samples to perform the basophil and mast cell activation studies to the various allergens. |
| Collaborator Contribution | The various partners will be consenting participants and send their anonymised clinical information as well as blood samples to KCL. |
| Impact | No outputs yet. |
| Start Year | 2020 |
| Description | UK Multicentre biomarker-led randomised-controlled trial of the basophil and mast cell activation tests in food allergy |
| Organisation | University Hospitals of Leicester NHS Trust |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have designed the study and will be distributing electronic clinical questionnaires as well as centralising the blood samples to perform the basophil and mast cell activation studies to the various allergens. |
| Collaborator Contribution | The various partners will be consenting participants and send their anonymised clinical information as well as blood samples to KCL. |
| Impact | No outputs yet. |
| Start Year | 2020 |
| Description | UK Multicentre biomarker-led randomised-controlled trial of the basophil and mast cell activation tests in food allergy |
| Organisation | University of Edinburgh |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have designed the study and will be distributing electronic clinical questionnaires as well as centralising the blood samples to perform the basophil and mast cell activation studies to the various allergens. |
| Collaborator Contribution | The various partners will be consenting participants and send their anonymised clinical information as well as blood samples to KCL. |
| Impact | No outputs yet. |
| Start Year | 2020 |
| Title | Basophil activation test to peanut |
| Description | The laboratory technique has been developed and validated for peanut allergy using samples from study ID 10020 in CRN Portfolio. Diagnostic performance and cut-off values have been determined and validated. It is currently being tested and validated to diagnose other food allergies, incluing milk, egg, sesame and cashew nut allergies. I would like to translate it to a clinical laboratory with the view of applying it to clinical practice. |
| Type | Diagnostic Tool - Non-Imaging |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2014 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| UKCRN/ISCTN Identifier | CRN Portfolio 10020 |
| Impact | This test will improve the accuracy of the diagnosis of peanut allergy and reduce the number of oral food challenges to peanut. |
| URL | https://clinicaltrials.gov/show/NCT03309488 |
| Description | Allergy UK Masterclass 2019 |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | The patient organisation and Charity Allergy UK organised a one-day event targeting health care professionals and patient groups. Experts in different aspects of allergic diseases shared their knowledge and expertise and answered questions. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Asthma UK Event |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Supporters |
| Results and Impact | 50 potential donors and members of the public attended this event, where PI and post-doctoral researchers presented about their research and showed them around the laboratories and research facilities. This event was very successful and significantly contributed for the funds needed for the renovation of the 5-year funding period of the centre. |
| Year(s) Of Engagement Activity | 2015 |
| Description | Asthma UK Fundraising Event |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | About 25 people who were either patients, relatives of patients or general public interested in asthma and allergy visited the department and the labs and had the opportunity to hear about recent research findings in asthma and allergy and had the opportunity to ask questions to the researchers and their teams. The event was organised by Asthma UK and raised interest and donations to this charity as a consequence. |
| Year(s) Of Engagement Activity | 2012,2016,2017,2018 |
| Description | Asthma UK event |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Type Of Presentation | Poster Presentation |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | About 100 people attended, including Asthma UK's new and existing major supporters, special events committee members and attendees, celebrity contacts and pharmaceutical company contacts. We showcased the work of the MRC & Asthma UK Centre for the Allergic Mechanisms of Asthma and the new Asthma UK Research strategy (incl. applied centre) and engaged the public, including people with asthma, with Asthma UK's research strategy. |
| Year(s) Of Engagement Activity | 2012 |
| Description | FARE Research Retreat for patients and public |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | • FARE Research Retreat for patients - lecture and Q&A about "Ex-vivo cellular activation assays in the diagnosis and monitoring of food allergy - online event, 21/09/2020 |
| Year(s) Of Engagement Activity | 2020 |
| Description | Global Atlas of Allergy |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | Yes |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I was an author of one of the chapters in this publication, which has been distributed to attendants of various scientific meetings organised by the European Academy of Allergy and Clinical Immunology. After this book was published I have been contacted by other researchers interested in my research field and I have been invited to expert panels regarding other initiatives of similar scope. |
| Year(s) Of Engagement Activity | 2014 |
| URL | http://www.eaaci.org/globalatlas/GlobalAtlasAllergy.pdf |
| Description | Interviewed for Allergic Living magazine |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | An interview for a magazine published for patients as the main target audience. The magazine is Canadian and has an international reach. It is published in print and also online, which allowed a wider reach, through not only the magazine's website but also social media. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.allergicliving.com/2019/01/16/new-food-allergy-tests-hold-hope-of-reliable-results/ |
| Description | Invited to an International Patient Group event |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | Invited to join expert panels in international days dedicated to food allergy organised by patient organisations and charities namely by the Food Allergy Research and Education (FARE) from the USA, to talk about the diagnostic tests that I have developed, namely BAT and MAT. |
| Year(s) Of Engagement Activity | 2018 |
| Description | MRC Asthma UK Centre Advisory Board Meeting |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | About 60 people attended the MRC & Asthma UK Centre Advisory Board Meeting where selected Principal Investigators, Post-doctoral researchers and PhD students presented their research to the Advisory Board members and the general audience. This was an opportunity to show case the research and collaborations within the Centre and beyond. |
| Year(s) Of Engagement Activity | 2014,2018 |
| Description | MRC Centenary Open Week Observation Point |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | Yes |
| Type Of Presentation | Workshop Facilitator |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | About 100 members of the public visited the stations we had with information about the research developed at the MRC & Asthma UK Centre in Allergic Mechanisms of Asthma. The members of the public were quite engaged with the activities we promoted on site, such as peak-flow measurements, models of molecules related to Allergy and a big inflatable lung with examples of diseases that can affect this organ. |
| Year(s) Of Engagement Activity | 2013 |
| Description | Talk for FARE and iFAAA |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | A group of experts, industry partners and patient organisation leads and individual patients got together in a one day event which consisted of presentations and Q&A sessions about food allergy and anaphylaxis. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Virtual Food Allergy Fund Summit 2020 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | Online Lecture "New approaches to the diagnosis of peanut allergy" at the Virtual Food Allergy Fund Summit 2020, 14th May 2020 |
| Year(s) Of Engagement Activity | 2020 |