WP 3.3 - Absorption of Tc99-labelled proteins from mouth and stomach in food allergic patients

Background:

The first local symptom of an allergic reaction in the vast majority of food allergic patients is oral itching (The Oral allergy syndrome, OAS). In some patients this reaction propagates further to a systemic reaction, whereas others only experience non-spreading local symptoms. Similarly, some sensitized bee and wasp allergic patients develop local reactions in the skin only, whereas others develop systemic anaphylaxis.

 

Hypothesis:

Confirming the initial findings by Prausnitz and Küstner in 1921, we have previously demonstrated that allergen absorption can occur via the oral mucosa resulting in measurable serum levels within 10 minutes. These kinetics, however, do not fully match those of anaphylactic shock, where death can occur within a few minutes after allergen intake.

 

The hypothesis in PART A is, that local mast cell populations are activated enabling mucosal uptake and that afferent nerves are concomitantly stimulated. This will be investigated in collaboration with two EU project by use of oral and gastric lavage with measurement of mediators such as histamine in the fluid. The hypothesis to be investigated in PART B is, that neurogenic factors as well as absorption factors are involved in the in the dissemination of the reaction. In this workpackage we shall focus on the true kinetics of uptake of allergens through the oral and intestinal mucosa and skin.

 

Methods:

We have recently developed a new and very sensitive technique based on isotope labeling (101In or 99Tc) of an innocent bystander (HSA or Transferrin), and this opens the possibility of safe and real time studies of absorption. The “innocent bystander protein”, albumin, will initially be used as marker for oral uptake of allergens by addition of labeled albumin to the challenge material. At a later stage, purified major allergen from peanut (Ara h2), produced in the framework of iFAAM will be used both for challenge and for labeling. Labeled gliadins will be assessed in patients with WDEAI (WP 2.2). Absorption of labeled wasp venom will be used for studies on cutaneous absorption.

Update 2016

Oral food challenges: is the interval between dose increments adequate? – Studies based on a human model of passive cutaneous anaphylaxis

Mose AP1,2, Mortz CG1,2, Eller E1,2 and Bindslev-Jensen C1,2

 

1) Odense Research Centre for Anaphylaxis (ORCA)

2) Department of Dermatology and Allergy Centre, Odense University Hospital, Denmark

 

 

Background: Titrated oral food challenges are the gold standard for diagnosing food allergy. Mounting evidence based on first-hand clinical experience and recent studies indicate that the internationally recommended, minimum time interval between dose steps is too short.

 

Objective: The purpose of this study was threefold: first, to determine if the level of s-IgE has an impact on the reaction time in the allergic response; second, to clarify if the quantity of the challenge dose affects the reaction time in the allergic response; third, to investigate the dose relationship between the size of IgE-mediated cutaneous reactions and the challenge dose.

 

Methods: We injected human donor sera containing contrasting levels of s-IgE to peanut intradermally into non-allergic individuals. Thereon, oral challenges with different doses of peanut were carried out in the recipients of the donor sera.

 

Results: The median reaction times for one of the donor sera (s-IgE to peanut 60.1 kIU/L) in a five-fold serial dilution ranged from 19 min (undiluted serum) to 53 min (dilution containing 1 % serum). The median reaction times for four donor sera with different s-IgE levels to peanut (7.5-93.1 kIU/L) varied between 16 min for the sera with highest level of IgE (range 11-48 min) to 34 min (range 23-56 min) for the sera with the lowest level. In the challenges with the different doses of peanut (1 g, 3 g, 10 g and 100 g), the median reaction times decreased (42 min, 36 min, 16 min and 9 min) with increasing doses; contrarily, the median wheal sizes increased (11 mm, 21 mm, 32 mm and 34 mm).

 

Conclusion: Higher levels of s-IgE and increasing challenge doses decrease the time to reaction and augment the response of IgE-mediated cutaneous reactions in our human model of passive cutaneous anaphylaxis.

 

 

 

 

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