Background: The prevalence of peanut together with tree nut allergies have increase over
the years and accounts for most of the life-threatening reactions even to minute doses of
the allergen. Consequently, peanut and tree-nut allergies cause significant physical and
mental burden to patients and their caretakers due to anxiety and fear of anaphylaxis
from accidental exposures, stress from following a strict elimination diet, lack of
proactive management plan and due to the low probability of natural recovery of such
allergies. For decades, the management relied on a strict avoidance of the culprit foods.
Oral immune therapy (OIT) is a ground breaking alternative modality to strict avoidance
diets. OIT consist of gradual introduction of low doses of the implicated food allergen
with the aim to modulate the patient's immune response and help build immunological and
clinical tolerance. Though OIT has its strong advantages, the clinical outcome is
variable among the patients. Therefore, there is a clear need for reliable ex-vivo
biomarkers that are reflective of the clinical progression and therapy outcome that could
aid with a more accurate patient stratification for personalized treatment approaches in
the future.
Aims: This project aims at measuring immune targets, antibodies, immune cells and immune
mediators, in patients' blood during oral food challenges (OFCs) and during the course of
standard-of-care oral immunotherapy to identify new immune markers correlating to with
the clinical outcome of the treatment. The identification of immune modifications during
OIT will allow us to endotype patients and possibly aid in unraveling markers of food
challenges and therapy progression as well as OIT outcome.
Luxembourg partners: The Luxembourg Institute of Health (LIH), Department of Infection
and Immunity (DII; head Prof. M. Ollert) has the scientific project lead (Principal
Investigator Dr. A. Kuehn). Main clinical partners are Dr. F. Codreanu-Morel and Dr. V.
Petit-Cordebar from the National Unit of Immunology-Allergology, Centre Hospitalier
(CHL), Luxembourg. Medical Principal Investigator for healthy controls is Dr. Alessia
Pochesci, MD, Clinical and Epidemiological Investigation Center (CIEC), Luxembourg
Institute of Health (LIH), Luxembourg. The Integrated Biobank of Luxembourg (IBBL) will
prepare and store a subset of clinical samples until use. Other biological samples are
prepared and stored at DII, LIH. Clinical samples (blood, sera, plasma,stool) will be
analyzed at DII, LIH.
Project implementation: The clinicians at CHL will perform detailed clinical examinations
of participants including skin prick test (SPT), serological analysis for specific IgE
and food challenges to the implicated food allergen as per their routine clinical
practice at the National Unit of Immunology-Allergology (CHL). Based on the European
Academy of Allergy and Clinical Immunology (EAACI) guidelines and procedures established
at CHL, all peanut- and tree-nut-allergic participants eligible for the study will
undergo a baseline OFC. OFC is adapted from PRACTALL protocol and allergen doses are
adjusted according to the clinical reactivity of the patient.
For participants eligible for immunotherapy (N= 30 Peanut-OIT and N=30 Tree nut-OIT), the
OIT is based on the established protocol at the clinic and adapted from the current
literature. Briefly, participant ingest incremental doses of the allergen (peanut/tree
nut) at home until they reach a maintenance dose of 300 mg nut-protein in approximately
26 weeks (6 months). This initial phase of OIT is termed as the build-up phase. This is
then followed by continued daily intake of this maintenance dose. After a minimum of 12
months of the maintenance phase of OIT, participants undergo another final OFC at the
hospital to assess for desensitization to peanut or tree nut. Participants follow up at
the hospital every 6 months i.e at end of the build-up phase, after 6 months and after 12
months of daily intake of maintenance dose.
Participants who are not eligible for OIT (N=30 peanut and tree-nut allergic) and who are
on avoidance diet, are also followed up every 6 months for 18 months. However, final OFC
will not be done for these participants.
The data collection of the study participants is carried out by the medical lead.
In addition, healthy adults (N=20) tolerating any type of nut and without any known food
allergies will be recruited as controls. Dr. Alessia Pochesci, CIEC, LIH is responsible
for the data collection from these healthy participants.
Blood sample collection:
i) For OIT group:
During the baseline and final OFC , blood samples will be collected at the
beginning, during and at the end of the food challenge in three different vials.
During OIT follow-up, a one-time blood sample will be collected at the end of the
build-up phase and after 6 months of maintenance phase in addition to the routine
blood collection during these follow-up visits.
ii) For avoidance group:
During the baseline OFC , blood samples will be collected at the beginning, during
and at the end of the food challenge.
During follow-up visits, one-time blood sampling will be taken six monthly i.e. at
6, 12 and 18 months after the baseline OFC.
iii) Healthy Adult participants: A one-time blood sampling will be done.
Stool sample collection:
Stool sample will be collected from nut-allergic participants at baseline and after the
completion of a minimum of 18 months of the study duration using commercial at-home stool
sampling kits. Participants receive a collection kit, containing special sampling tubes,
accessories and instructions.
Collected clinical samples will be pseudonymized at the clinical centers. A synonym list
containing the information on the identify of the participants recruited and their
corresponding pseudonym, will be available at the clinical center only (medical
investigators). Personal data is protected under the regulation (EU) 2016/679 of 27 April
2016 on the protection of individuals with regard to the processing of personal data
(GDPR) and the law of 1 August 2018 on the organization of the National Data Protection
Commission and the General Data Protection Act.