Enquiring About Tolerance (EAT) study: Feasibility of an early allergenic food introduction regimen.

BACKGROUND: The influence of early exposure to allergenic foods on the subsequent development of food allergy remains uncertain. OBJECTIVE: We sought to determine the feasibility of the early introduction of multiple allergenic foods to exclusively breast-fed infants from 3 months of age and the effect on breastfeeding performance. METHODS: We performed a randomized controlled trial. The early introduction group (EIG) continued breastfeeding with sequential introduction of 6 allergenic foods: cow's milk, peanut, hard-boiled hen's egg, sesame, whitefish (cod), and wheat; the standard introduction group followed the UK infant feeding recommendations of exclusive breastfeeding for around 6 months with no introduction of allergenic foods before 6 months of age. RESULTS: One thousand three hundred three infants were enrolled. By 5 months of age, the median frequency of consumption of all 6 foods was 2 to 3 times per week for every food in the EIG and no consumption for every food in the standard introduction group (P < .001 for every comparison). By 6 months of age, nonintroduction of the allergenic foods in the EIG was less than 5% for each of the 6 foods. Achievement of the stringent per-protocol consumption target for the EIG proved more difficult (42% of evaluable EIG participants). Breastfeeding rates in both groups significantly exceeded UK government data for equivalent mothers (P < .001 at 6 and at 9 months of age). CONCLUSION: Early introduction, before 6 months of age, of at least some amount of multiple allergenic foods appears achievable and did not affect breastfeeding. This has important implications for the evaluation of food allergy prevention strategies

Novel detection of in vivo HLA-B27 conformations correlates with ankylosing spondylitis association

Objective. The class I major histocompatibility complex (MHC) molecule HLA-B27 exhibits a strong association with the autoimmune inflammatory arthritis disorder ankylosing spondylitis (AS) and with other related spondylarthropathies. In the absence of both a defined autoimmune response and a target autoantigen(s), the propensity of HLA-B27 to misfold has been hypothesized to be a major parameter in disease pathogenesis. We undertook this study to test the hypothesis that HLA-B27 misfolding is due to exposure of cysteine residues within the heavy chain to the oxidizing environment of the endoplasmic reticulum. Methods. A rapid acidification and alkylation modification method was used to examine cysteine residue exposure and accessibility within AS-associated and non-AS-associated HLA-B27 subtypes. Results. This novel approach to probing in vivo class I MHC structure revealed that the HLA-B27 heavy chain adopts conformations not previously described. Furthermore, amino acid residues specific to subtypes HLA-B*2706, B*2709, and B*2704 can have an impact on these novel conformations and on cysteine residue exposure. Conclusion. HLA-B27 can adopt novel conformations, resulting in differential accessibility of cysteine residues, which can explain the propensity to misfold. Cysteine exposure in the HLA-B27 heavy chain is also affected by residues within the 114 and 116 regions, thereby providing a potential biochemical basis for the association of HLA-B27 subtypes with AS.</p