Proteolysis of the peanut allergen Ara h 1 by an endogenous aspartic protease
The 7S and 11S globulins of peanuts are subjected to proteolysis two days after seed imbibition, with Ara h 1 and the arachin acidic chains being among the first storage proteins to be mobilized. Proteolytic activity was greatest at pH 2.6-3 and is inhibited by pepstatin A, characteristic of an aspartic protease. This activity persists in seedling cotyledons up to at least 8 days after imbibition. In vitro proteolysis of Ara h 1 at pH 2.6 by extracts of cotyledons from seedlings harvested 24 h after seed imbibition generates newly appearing bands on SDS-PAGE. Partial sequences of Ara h 1 that were obtained through LC-MS/MS analysis of in-gel trypsin digests of those bands, combined with information on fragment size, suggest that proteolysis begins in the region that links the two cupin domains to produce two 33/34 kD fragments, each one encompassing an intact cupin domain. The later appearance of two 18 and 10/11 kD fragments can be explained by proteolysis within an exposed site in the cupin domains of each of the 33/34 kD fragments. The same or similar proteolytic activity was observed in developing seeds, but Ara h 1 remains intact through seed maturation. This is partly explained by the observation that acidification of the protein storage vacuoles, demonstrated by vacuolar accumulation of acridine orange that was dissipated by a membrane-permeable base, occurs only after germination. These findings suggest a method for use of the seed aspartic protease in reducing peanut allergy due to Ara h 1.
Sensitisation to milk, egg and peanut from birth to 18 years: a longitudinal study of a cohort at risk of allergic disease
BACKGROUND: Longitudinal data on the natural history of food sensitisation beyond early childhood are scarce. We aimed to investigate the natural history of milk, egg and peanut sensitisation from infancy to18 years and assess whether early food sensitisation predicted adolescent food allergy. METHODS: Sensitisation to cow's milk, hen's egg and peanut was measured by skin prick testing at ages 6 months, 1, 2, 12 and 18 years in a high risk allergy birth cohort (n=620). Generalized additive models investigated interactions with sex, eczema and aeroallergen sensitisation in infancy. Logistic regression assessed the relationships between early food sensitisation and adolescent sensitisation and probable food allergy up to 18 years. RESULTS: The prevalence of egg and peanut sensitisation peaked at 12 months, while milk sensitisation peaked at both 1 and 12 years. Boys with early eczema had the highest prevalences of milk and egg sensitisation throughout follow-ups. However, neither sex nor eczema influenced the prevalence of peanut sensitisation over time. New onset food sensitisation beyond the age of 2 was observed in 7% of participants. Food sensitisation at 12 months was associated with increased risk of adolescent food sensitisation and adolescent probable food allergy, with sensitisation to more than one food allergen had the strongest predictor. CONCLUSIONS: Food sensitisation prevalence is highest in infancy and declines after 12 months of age. Boys with early life eczema have the highest prevalence of milk and egg sensitisation. Food sensitisation at 12 months can predict children at greater risk of adolescent sensitisation and probable food allergy at 12 and 18 years.
Recent advances in immunotherapy and vaccine development for peanut allergy
Peanut allergy is a common problem and can be the cause of severe, life-threatening allergic reactions. It rarely resolves, with the majority of patients carrying the disease onto adulthood. Peanut allergy poses a significant burden on the quality of life of sufferers and their families, which results mainly from the fear of accidental peanut ingestion, but is also due to dietary and social restrictions. Current standard management involves avoidance, patient education and provision of emergency medication, for use in allergic reactions, when they occur. Efforts have been made to develop a vaccine for peanut allergy. Recent developments have also highlighted the use of immunotherapy, which has shown promise as an active form of treatment and may present a disease-modifying therapy for peanut allergy. So far, results, especially from oral immunotherapy studies, have shown good efficacy in achieving desensitization to peanut with a good safety profile. However, the capacity to induce long-term tolerance has not been demonstrated conclusively yet and larger, phase III studies are required to further investigate safety and efficacy of this intervention. Peanut immunotherapy is not currently recommended for routine clinical use or outside specialist allergy units.