Immune mechanisms of food allergy and its prevention by early intervention

Abstract

The environmental factors driving the increase in food allergies are unclear and possibly involve dual exposure to allergens, microbiome-driven effects or other mechanisms. Until they can be better understood, early intervention aiming at establishing oral tolerance provides an effective way to decrease the window-of-risk when children may develop allergic sensitisation to foods due to the absence of a protective immune response. Thus, the recent LEAP (Learning Early About Peanut allergy) and LEAP-On studies achieved a high level of peanut allergy prevention by early introduction of peanuts in the infants diet and conveyed more information regarding the evolution of IgE and IgG4 antibody responses to food antigens over time.

Figure 1

Changes that occur with IgE, IgG and IgE:IgG4 ratios over time in children who consumed or avoided peanuts in the frame of the LEAP and LEAP-On studies [39]. The red lines outline the evolution of the levels of peanut-specific IgG4 and respectively the evolution of the ratio of peanut-specific IgG/IgE in children who were subsequently found to be peanut allergic at 72 months of age.

Figure 2

Depletion of IgG4 decreased the ability of plasma from peanut-sensitized but clinically tolerant patients to inhibit peanut-induced activation of mast cells. **p<0.01 [17] In these inhibition experiments, LAD2 mast cells were sensitized with plasma from a patient with peanut allergy, then were activated with peanut allergens in the presence of either IgG4-depleted or mock-depleted plasma from 12 peanut-sensitized but clinically tolerant individuals. The vertical axis shows the percentage of inhibition of mast cell activation achieved by adding the respective plasma samples.