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research-project
Research project

IDEAL: Improvement of Diagnostic mEthods for ALlergy assessment.

Status: Start date:01-04-2012 End date: 01 04 2021

The hypothesis pertinent to this proposal is that an accurate history, IgE antibodies in the serum and positive SPT, and more advanced techniques might predict clinical allergy to cashew nuts.

What we do

About our project

This project
This project will present an unique opportunity to investigate the potential of less invasive allergy diagnostic tests, in particular cell-based assays, and validate these tests against the clinical background. A new approach of diagnosing food allergy is the use of component resolved diagnosis (CRD), which comprises the determination of IgE by ELISA that recognises isolated allergenic proteins, which are either produced by recombinant expression of allergen-encoding cDNAs or by purification from natural allergenic foods.


Optimization of the diagnosis of cashew nut allergy; development of new diagnostic tools
Improved Mediator Release Assays (MRAs) will be developed e.g. basophil activation test (BAT) and rat basophil leukaemia test (RBL). The researchers aim to optimize the diagnosis of nut allergy, by using the different components: 1) history, 2) conventional markers of sensitization, 3) MRA’s and 4) CRD i.e. IgE-levels of Ana o 1, Ana o 2 and Ana o 3, to finally predict the outcome of the DBPCFC. Measure the effect of improved diagnostic procedures on quality of life.

Develop a diagnostic model with new Mediator Release assays to predict the outcome of the DBPCFC
Predictive modelling and regression techniques will be used to accomplish and identify the optimal set of diagnostic procedures for the diagnosis of cashew nut allergy. In fact, these models might be useful for other nuts as well. In that way it will accomplish a breakthrough in the diagnosis of food allergy.

Cross reactivity between cashew nuts and other allergens
The question will be addressed as to whether cashew nut is the primary sensitizing agent in cashew nut allergy. For that purpose a profile of co-sensitizing allergens (e.g. peanut, other nuts, and mango) needs to be accomplished. Because most reported cashew allergies are severe, the mechanisms of cashew nut and cross reactivity will be studied in more detail.

Our research focus

MRA’s
Mediator Release Assays may circumvent, in particular in the setting of food allergies, the drawbacks of on the one hand IgE-based assays (‘overly’ simple leading to an unacceptably high level of erroneous outcomes), Skin Prick Test (SPT) (confounding cross-reactions, instability of allergens, thus erroneous outcomes) and on the other hand DBPCFC, which is expensive, burdensome, no resolution at level of allergenic protein, potentially not without risk. Therefore, MRA’s e.g. BAT and RBL might predict the Cashew allergy better that the conventional tests.

BAT
The basophil activation test (BAT) is performed with patient’s own IgE-loaded basophilic cells, which are subsequently exposed to functional, cross-linking-capable, allergen preparations.

RBL
The rat basophil leukemia test (RBL) makes use of a (rat-derived) cell line that expresses the human Fcε-receptor (FcεR). These cells can be ‘loaded’ with IgE from a patient’s serum, an operation that can be done in a stage at which a certain number of sera (that can stably be stored for long intervals) can be analysed simultaneously. RBL-cells can be used as a ‘vehicle’ to analyse any type of food allergy, provided suitable allergen preparations are available.

Prognostic model
The strategy aims to develop a diagnostic model that can provide accurate predictions for future patients rather than predictions that are correct for the patients of the development dataset. We hypothesize that MRAs are superior to other tests in predicting clinically important allergy to cashew nuts. Superiority will justify their use and may lead to displacement of other diagnostic procedures. To this purpose, predictive modelling and regression techniques will be used to accomplish and identify the optimal set of diagnostic procedures for the diagnosis of cashew nut allergy.

Funds & Grants

Technology Foundation STW (STW number 11868),
Food Allergy Foundation,
Siemens Healthcare Diagnostics,
HAL Allergy,
Intersnack the Netherlands B.V.,
ALK-Abello B. V.,
and the Netherlands Anaphylaxis Network funded this project

Collaborations

Internal collaboration:

Laboratory of Immunology
Paediatric allergology
Kinderhaven, Havenziekenhuis

 

External collaboration:

WUR, Food and Biobased Research; Wageningen
Reinier de Graaf Gasthuis, Delft
UMCG; Groningen

Publications

J.P.M. van der Valk, R. Gerth van Wijk, A.E.J. Dubois, H. de Groot, M. Reitsma, B. Vlieg-Boerstra, H.F.J. Savelkoul, H.J. Wichers, N.W. de Jong. Multicentre double-blind placebo-controlled food challenge study in children sensitized to cashew nut. PLoS One. 2016 Mar 11;11(3):e0151055.

J.P.M van der Valk, R. Gerth van Wijk, N.W. de Jong. Failure of introduction of cashew nut after a negative oral food challenge test in children. Pediatr Allergy Immunol. 2016 Sep;27(6):654-8.

P.M. van der Valk, R. Gerth van Wijk, BMJ Flokstra-de Blok, J.L. van der Velde, H. de Groot, H.J. Wichers, A.E.J. Dubois3, N.W. de Jong. No difference in health-related quality of life, after a food challenge with cashew nut in children participating in a clinical trial. Pediatr Allergy Immunol. 2016 Aug 6.

J.P.M. van der Valk, R. Gerth van Wijk, J. L. Baumert, J.A. Nordlee, B. Vlieg-Boerstra, H. de Groot, A.E.J. Dubois, N.W. de Jong. Threshold distribution and eliciting dose of cashew nut allergy. Ann Allergy Asthma Immunol. 2016 Oct 20.

J P.M. van der Valk, R Gerth van Wijk, Y Vergouwe, Ewout W. Steyerberg, M Reitsma, H J. Wichers, H F.J. Savelkoul, B Vlieg-Boerstra PhD RD5, H de Groot, A E.J. Dubois, N W. de Jon. IgE Ana o 1, 2 and 3 accurately distinguish tolerant from allergic children sensitized to cashew nuts. Clin Exp Allergy. 2017 (47);

J.P.M. van der Valk, R. el Bouche, R. Gerth van Wijk, H. de Groot, H.J. Wichers, A.E.J. Dubois, N.W. de Jong 1 "Low percentage of clinically relevant pistachio nut and mango co-sensitisation in cashew nut sensitised children" Clin Transl Allergy. 2017 Mar 20;7:8

Our team

Dr.N.W. de Jong n.w.dejong@erasmusmc.nl
Prof dr.R. Gerth van wijk r.gerthvanwijk@erasmusmc.nl
Dr.H.van der Valk h.kuipervandervalk@gmail.com
Dr. B.J. Vlieg-Boerstra b.j.vlieg-boerstra@amc.uva.nl
Prof dr. E.W. Steyerberg e.steyerberg@erasmusmc.nl
Dr. Y.Vergouwe y.vergouwe@erasmusmc.nl
L. Groenendijk lgroenendijk87@hotmail.com
Prof dr. H. Wichers harry.wichers@wur.nl
Dr. Marit Reitsma marit.reitsma@wur.nl
Drs.S.Bastiaan-Net shanna.bastiaan@wur.nl
Prof dr Huub Savelkoul huub.savelkoul@wur.nl
Prof dr A.E.J. Dubois a.e.j.dubois@bkk.umcg.nl
Dr.Dorien van Ginkel cd.vginkel@gmail.com
Dr. B.M.J. Flokstra- de Blok b.m.j.de.blok@med.umcg.nl