Development of improved peanut serum-based allergy diagnostics by preventing false-positive outcomes induced by specific IgE of sensitized but tolerant subjects. By means of our study results, improved allergens (i-allergens) for the diagnostic may…
ID
Source
Brief title
Condition
- Allergic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Since this is an explorative study, the primary outcome will be divided in a
discovery and a validation outcome.
1) Discovery outcomes
For characterization of obtained Ara h 2, 6 and 7 specific IgE-antibodies from
sensitized but tolerant and genuine allergic subjects, the epitope specificity
will be examined. These outcomes will be the basis to evaluate the recognition
of epitope combinations in Ara h 2, 6 and/or 7 sensitized subjects with allergy
or tolerance.
2) Validation outcomes
To confirm the discovery outcome, the functionality of the antibody
combinations (* epitope combinations) will be investigated by loading the as
relevant characterized antibody combinations on effector cells and stimulating
them with the allergen of interest. The property to induce an allergic reaction
will be measured by the release of mediators or the upregulation of surface
maker on the effector cells.
Secondary outcome
Since additional parameters might influence the induction of an allergic
reaction, the binding affinity of IgE antibodies and the epitope specificity of
antibodies with another isotype will be measured. Their acquirement to inhibit
an allergic reaction will be estimated by mediator release assay or up
regulation of surface maker.
Contiguous to the primary and secondary parameters, new linear and
conformational epitopes may be identified.
Additionally, symptoms during an allergic reaction differ between allergic
subjects and the potential antibody combinations can vary accordingly. Fewtrell
and Metzger, 1980, showed a greater histamine release after forming
cross-linked oligomers instead of dimers [16]. Possibly, we can find hints why
some subjects have stronger reactions than others.
Background summary
Food allergy is a medical problem affecting 2-3 % of the population with an
increasing tendency. To date, the gold standard in food allergy diagnostic is
the double blind, placebo controlled food challenge (DBPCFC) exhibiting major
drawbacks, such as the risk to develop a life-threatening allergic reaction,
high costs and time consumption. Diagnostics using specific IgE can overcome
these drawbacks, but can lead to false negative and false positive results. In
the diagnostics of anti-neutrophil cytoplasmic antibody (ANCA)-associated
vasculitis, improved diagnostics tools were developed by categorizing epitopes
in disease-related and natural ones. Thus, we hypothesize the existence of
allergy-related epitope combinations since an allergic reaction is induced by
cross-linking of at least two high affinity IgE-receptors (Fc*RI) on the
surface of mast cells, basophils and eosinophils.
Study objective
Development of improved peanut serum-based allergy diagnostics by preventing
false-positive outcomes induced by specific IgE of sensitized but tolerant
subjects. By means of our study results, improved allergens (i-allergens) for
the diagnostic may be developed.
Study design
It is an explorative study and the included subjects will come for one visit to
withdraw 100 ml blood. The blood is used to generate monoclonal antibodies
specific for the major peanut allergens Ara h 2, 6 or 7.
Study burden and risks
The most common side effect is a small discoloration or bruise remaining at the
site for several days. There may be mild temporary pain associated with the
insertion of the needle. In very rare cases, a local infection may occur at the
site of the venipuncture. The subject will be informed about possible slight
pain and discomfort with the blood withdrawal.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
- At least 18 years of age
- Detectable IgE-sensitization to at least one of the allergens Ara h 2, 6 and 7
- Positive performed peanut food challenge for allergic patients
- Negative performed peanut food challenge or convincing history for tolerant patients
Exclusion criteria
- Pregnancy
- Previously or current participation in an allergy immunotherapy trial
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL63917.041.17 |