Exploring the Immunological Basis in the Evolution of Tree Nut and Peanut Allergy During Treatment Care for Understanding Markers and Treatment Targets

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.