Allergy最新文献

Allergic reactions to foods are primarily driven by allergen-binding immunoglobulin (Ig)E antibodies. IgE-expressing cells can be generated through direct switching from IgM to IgE or a sequential class switching pathway where activated B cells first switch to an intermediary isotype, most frequently IgG1, and then to IgE. It has been proposed that sequential class switch recombination is involved in augmenting the severity of allergic reactions, generating high affinity IgE, differentiation of IgE plasma cells, and in holding the memory of IgE responses. We directly tested these possibilities by comparing the allergic immunity of wild-type and IgG1-deficient (hMT) mice. We found that sequential switching through IgG1 was not required to maintain the binding capacity of IgE nor for its ability to promote degranulation and elicit anaphylaxis against bona fide food allergens. Furthermore, the absence of sequential switching modestly impacted IgE affinity and clinical reactivity against hapten antigens, suggesting that the nature of the antigen impacts the requirement for sequential switching. At a cellular level, the capacity to undergo sequential switching through IgG1 provided no competitive advantage for subsequent IgE expression among germinal center B cells or plasma cells. Furthermore, the recall of allergic immunity at memory timepoints was preserved in the absence of sequential switching through IgG1, a finding that corresponded with intact type 2 memory B cell polarization. Together, these data demonstrate that sequential switching through IgG1 is redundant in sensitization, anaphylaxis, and the persistence of allergy, ultimately revealing that IgE derived from any switching source should be targeted by novel therapeutics seeking to ameliorate allergic diseases.

Background: Intestinal barrier dysfunction may lead to a break in tolerance and development of food allergy (FA). There is contradictory evidence on whether intestinal permeability (IP) is altered in IgE-mediated FA. Thus, we sought to determine whether IP differed between children with eczema who did (FA group) or did not (atopic controls, ACs) develop FA and whether peanut sensitization, allergy, and early introduction impacted IP using serum biomarkers zonulin, soluble CD14, and Intestinal Fatty Acid Binding Protein among randomly selected participants enrolled in the Learning Early About Peanut allergy trial.

Methods: FA group was defined as having at least one FA at either baseline (4-11 months) or 60 months of age (V60). ACs had eczema at baseline and no FA at either visit. Serum IP markers (sIPMs) were measured by ELISA at baseline and V60, and their relationship with the clinical characteristics of participants was analyzed using parametric tests and linear regression models.

Results: We evaluated 237 FA subjects and 76 ACs. sIPM levels were similar in FA subjects and ACs at baseline and V60. Age when the child first developed any FA (< 1 year vs. > 1 year), eczema severity, peanut sensitization, peanut allergy, and early peanut introduction were not statistically significantly associated with sIPM levels. Total IgE and eosinophil levels, peanut-specific IgE, IgG4, and IgG4/IgE ratio were not correlated with sIPM levels.

Conclusions: No differences in sIPMs were detected to support altered IP in infants with FA compared to ACs or following early peanut introduction among peanut-sensitized children.