The development of new diagnostic tools in food allergy

The diagnosis of food allergy is difficult since the specificity and positive
predictive value of routine tests (specific IgE in the blood, skin test) is
low. This results in many false-positive results. The gold standard, the
double-blind food challenge, is a time consuming and expensive diagnosis and
also a burden for the patient. Therefore, the Minister of Health was advised by
the Health Council in 2007 that research had to be conducted that can lead to
the development of better tests for the diagnosis of food allergy.
Until now, the diagnosis is made using extracts of whole food. At this moment,
many specific allergenic proteins are isolated and available for diagnosis. In
some recent studies on apple and hazelnut allergy, it was showed that the
severity of an allergic reaction can be better predicted when based on these
components than using current diagnostic techniques. With a new developed
allergen chip (ImmunoCAP ISAC) 103 allergenic components can be tested with a
small amount of serum from the patient. By using this allergen chip we are able
to determine for the major allergenic foods whether this new form of diagnosis
is an improvement compared to current diagnostic techniques. We will do this by
identifying the major allergen components in a retrospective study using a
patient population already well characterized. Then we will perform a
prospective study and analyse these data on allergen components combined with
anamnestic factors to develop a model to further optimize the diagnosis.
In recent research in collaboration with TNO Quality of Life we found
indications that it is possible by using metabolomics (the measurement of
metabolites) to find new biomarkers that can predict whether there is a food
allergy or not and its severity. Therefore we want to investigate whether we
can identify biomarkers and further improve the aforementioned model.

The study consists of three parts:
a) Determine which specific components of a food allergen are important for
(the severity of) the reaction.
b) Developing a model to predict the severity of a food allergy using specific
components (obtained from part a) combined with the other components (inhalant
and other food allergens) and data from patients' history.
c) Identifying new biomarkers to further improve the aforementioned model and
the use of experimental allergy tests.

Part a: case-control, retrospective. Due to the exploratory nature of this
section, we will Include as many patients as possible to determine which
allergenic components are important in predicting an allergy. We will include a
minimum of 30 patients per allergen (legumes, nuts, cow's milk, egg, shrimp,
fish and latex (because of the associated food alelrgy). Depending on whether
there is serum available from these patients from a previous study
investigating the diagnosis of food allergy or a clinic visit, there will be a
venepuncture to test the allergen components.
-Part b: cohort study ,prospectively. Patients that visit the outpatient clinic
of Dermatology / Allergology complete a standardized questionnaire and a
venepuncture will take place to test the allergenic components. A skin prick
test will be performed when it has not already been done at the outpatient
clinic. Also in this part, we want to include for each food as many patients as
possible to test as many combinations of components combined with anamnestic
factors as possible.
-Part c: cohort study. In patients that will undergo a food challenge, blood,
urine and saliva will be tested for the investigation of a new biomarker.

The burden for most patients will consist of an oupatient clinic visit of about
30 minutes were a venepuncture will be performed and a questionnaire will be
reviewed that has already routinely been completed by the patient. The risks of
the venepuncture are negligible. The skin prick test, a routine test that
usually has already been performed, causes itchy bumps that gradually disappear
after half an hour. There is a low risk of a mild or severe allergic reaction
(very rare).
Patients who undergo a food challenge will be two full, non-consecutive days at
the dermatology department in the UMCU. The food challenge is the best test to
determine a food allergy. With this test, which is performed according to
internationally established guidelines, increasing doses of food is
administered to the patient until it is clear whether there is an allergy and
to what extent. The challenge is stopped when a clear objective symptom will
take place or a severe, persistent subjective complaint that lasts for longer
than 45 minutes. We have extensive experience with this test and it is
routinely used in the diagnosis of food alelrgy. Our experience learns us that
the reactions that occur are usually mild, an anaphylactic reaction is rarely
observed. Before the start of the challenge, patients get an infusion needle
for quick medical action when needed to treat the allergic reaction. After the
food challenge, patients are observed for at least 2 hours.