Allergenicity assessment of novel foods - lessons from immune endotyping of food-allergic patients

Novel foods (NF), defined as foods not commonly consumed in Europe before May 1997, represent a growing area of interest in the pursuit of sustainable and nutritionally valuable diets. Before introduction to the market, however, their safety needs to be clearly demonstrated. Food allergy (FA) represents a significant public health burden and may also extend to NF. Regarding FA risk, the current guidelines for NF safety assessment address possible cross-reactivity with known allergens but offer little direction when allergenic potential is unknown. Conventional approaches such as specific IgE testing, often fail to predict clinically relevant immune responses in humans. In vitro platforms based on allergen-stimulated human immune cells allow advanced endotyping of FA patients through molecular and functional immune readouts. They might distinguish between FA, asymptomatic IgE sensitization and healthy states based on immune cell reactivity, via effector cells (e.g. CD63+ basophils), T cells (effector cells expressing high IL-5/IFN-γ ratios; CD154+CD69+ memory, CD137+CD154- regulatory, CD25+OX40+ activated CD4+ T cells) or complex signatures (e.g. Th2 cells, memory Treg cells, activated NK cells; homing marker expression including CCR4, CXCR3). We provide an overview of current immune cell-based stimulation assays allowing to differentiate and grade immune responses in samples from FA, sensitized and healthy individuals, on the basis of multi-omics approaches. Those may help identifying which immune markers are most relevant to measure in future cell line-based approaches, such as gut-on-a-chip assays, which represent an important strategy to assess safety of NF.