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)
- Benaroya Research Institute (Collaboration)
- Queen Mary, University of London, United Kingdom (Collaboration)
- National Institute of Allergy and Infectious Diseases (NIAID) (Collaboration)
- University of Lisbon (Collaboration)
- U.S. Department of Agriculture USDA (Collaboration)
- Thermo Fisher Scientific (Collaboration)
- University of Geneva, Switzerland (Collaboration)
- Valencia University, Spain (Collaboration)
Publications
Santos AF
(2015)
The need for patient-focused therapy for children and teenagers with allergic rhinitis: a case-based review of current European practice.
in Clinical and translational allergy
Dreborg S
(2013)
The history of pediatric allergy in Europe - from a working group to ESPACI and SP-EAACI.
in Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
Santos AF
(2016)
The expression of CD123 can decrease with basophil activation: implications for the gating strategy of the basophil activation test.
in Clinical and translational allergy
Panesar SS
(2013)
The epidemiology of anaphylaxis in Europe: a systematic review.
in Allergy
Hoffmann HJ
(2015)
The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease.
in Allergy
Skevaki CL
(2011)
The 10th anniversary of the Junior Members and Affiliates of the European Academy of Allergy and Clinical Immunology.
in Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
Santos AF
(2017)
Road map for the clinical application of the basophil activation test in food allergy.
in Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
Papadopoulos NG
(2012)
Research needs in allergy: an EAACI position paper, in collaboration with EFA.
in Clinical and translational allergy
Du Toit G
(2015)
Randomized trial of peanut consumption in infants at risk for peanut allergy.
in The New England journal of medicine
Hoffmann HJ
(2016)
Pros and Cons of Clinical Basophil Testing (BAT).
in Current allergy and asthma reports
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
Dhami S
(2014)
Management of anaphylaxis: a systematic review.
in Allergy
Santos AF
(2017)
Making the Most of In Vitro Tests to Diagnose Food Allergy.
in The journal of allergy and clinical immunology. In practice
Santos AF
(2015)
Is the use of epinephrine a good marker of severity of allergic reactions during oral food challenges?
in The journal of allergy and clinical immunology. In practice
Santos AF
(2016)
Is the Prevalence of Food Allergy Not on the Rise After All?
in The journal of allergy and clinical immunology. In practice
Jutel M
(2015)
International consensus on allergy immunotherapy.
in The Journal of allergy and clinical immunology
Turcanu V
(2017)
Immune mechanisms of food allergy and its prevention by early intervention.
in Current opinion in immunology
Santos AF
(2015)
IgG4 inhibits peanut-induced basophil and mast cell activation in peanut-tolerant children sensitized to peanut major allergens.
in The Journal of allergy and clinical immunology
Santos AF
(2012)
Food allergy and anaphylaxis in pediatrics: update 2010-2012.
in Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
Du Toit G
(2016)
Effect of Avoidance on Peanut Allergy after Early Peanut Consumption.
in The New England journal of medicine
Muraro A
(2014)
EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy.
in Allergy
Santos AF
(2015)
Distinct parameters of the basophil activation test reflect the severity and threshold of allergic reactions to peanut.
in The Journal of allergy and clinical immunology
Santos AF
(2013)
Commentary on 'glucocorticoids for the treatment of anaphylaxis'.
in Evidence-based child health : a Cochrane review journal
Santos AF
(2016)
Basophil activation test: food challenge in a test tube or specialist research tool?
in Clinical and translational allergy
Santos AF
(2014)
Basophil activation test discriminates between allergy and tolerance in peanut-sensitized children.
in The Journal of allergy and clinical immunology
Muraro A
(2014)
Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology.
in Allergy
Dhami S
(2016)
Allergen immunotherapy for the prevention of allergic disease: protocol for a systematic review.
in Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
Roberts G
(2016)
A new framework for the interpretation of IgE sensitization tests.
in Allergy
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 | 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 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 | 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 | MRC Centenary Early Career Award |
| Amount | £55,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2013 |
| End | 07/2013 |
| 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 | 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 | 06/2014 |
| 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/ |
| 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 | Basophil activation test in the LEAP and LEAP-On studies |
| Organisation | National Institute of Allergy and Infectious Diseases (NIAID) |
| 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 | 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 |
| 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 | 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 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 |