## 5 Why Are Baked Proteins Different?
[70] challenged 100 cow's milk allergic children (average age 7.5 years, range 2.1-17.3 years) with cow's milk baked in waffles or muffins. Seventy-five percent of the cow's milk allergic children tolerated baked milk. Those who tolerated baked milk were asked to consume products containing baked milk at home for three months and, then, were re-evaluated. Immune response (serum-specific IgE and IgG4), growth and intestinal permeability were also monitored. After three months, children consuming baked milk products had significantly smaller SPT and higher casein--IgG4 compared with baseline. On repeat challenges with uncooked cow's milk, the group of children who tolerated heated cow's milk outgrew their milk allergy quicker than the group who did not tolerate heated cow's milk in their diet [7]. [PERSON] [7] reported the results of the long-term follow-up of the group initially described by [PERSON]. The initial baked milk challenge was tolerated by 65 of 88 children. Compared with the children strictly avoiding milk, baked milk-tolerant children were more likely to become tolerant to unheated milk than baked milk-reactive children (Odds Ratio 2.8 (95% Confidence Interval, 4.8-162.7); \(p<0.01\)). No difference was noted in the milk-specific IgE levels between groups; however, both the casein IgE and \(\beta\)-lactoglobulin IgE values in the baked milk tolerant group decreased significantly over time. There was a significant increase in the median casein IgG4 value, but not the \(\beta\)-lactoglobulin IgG4 level from base line to final visit in the baked milk tolerant group. Eosinophilic esophagitis, which has been identified as a potential complication of SOTI [51], was reported in the baked milk study, but not the baked egg study. Two subjects in the active group and five in the comparison group had eosinophil esophagitis, but this was not related to the intervention. The baked egg and milk studies by [PERSON], [PERSON] _et al_. and [PERSON] _et al_. [8,9,70] are promising, but need substantiation, as the studies were not randomized controlled trials, and the results may be due to comparisons of different phenotypes of milk or egg allergy, changes with time or other unidentified confounders. Neither of the studies tested tolerance to the raw protein after a period of avoidance of the baked products, so it is unknown whether the effect was permanent. There are several advantages of using baked products as a mode of inducing tolerance to egg or cow's milk protein. Once tolerance to a baked product is proven, the child is able to include it in their diet on a regular basis. Compared with traditional SOTI protocols, this means that there is less cost in terms of hospital admission times and inconvenience to the family, as there is no intense \"up dosing\" phase required. This approach is potentially safer compared with protocols, which rely on parents making up and administering the appropriate diluted dose of the allergen at home. The ability to consume baked products also moves the child towards a more normal, less restricted diet. At present, there are no tests that predict tolerance to baked egg or baked milk proteins. Foods containing baked egg are reported to elicit anaphylaxis in egg allergic individuals, and as such, individuals chosen for this therapy should be carefully screened [9]. Furthermore, to date, there are few studies reporting immune mechanisms after oral immunotherapy, and this is one area that requires further research to help guide development of immunotherapy protocols. There is one study by [PERSON] _et al_. that has shown a significantly higher percentage of proliferating casein-specific CD25/CD271 T-cells (regulatory T-cells involved in tolerance induction) from casein-induced peripheral blood mononuclear cell cultures taken from extensively heated milk-tolerant children compared with cells from extensively heated milk-reactive children. They showed no significant difference between the groups in the frequency of polyclonal T-cells or casein-specific effector T-cells.