scholarly journals Mechanisms of allergen-specific B cell tolerance in children with cow’s milk-oral immunotherapy and natural outgrowth of milk allergy

Author(s):  
Pattraporn Satitsuksanoa ◽  
Willem van de Veen ◽  
Ge Tan ◽  
Oliver Wirz ◽  
Kirstin Jansen ◽  
...  

Abstract Antigen-specific memory B cells play a key role in the induction of immune tolerance to food allergens and clinical healing. Here, we characterized the role of allergen-specific B cells in immune tolerance induced by oral allergen-specific immunotherapy (OIT) and natural tolerance that developed in children who spontaneously outgrew cow’s milk allergy. Increased frequency of circulating milk allergen αS1-casein -specific B cells was observed after OIT and natural tolerance (NT). Milk desensitized subjects showed partial acquisition of tolerance phenotypic features induced tolerance, suggesting that desensitization is an earlier stage of tolerance. Immunoregulatory genes such as IL10RA and IGHG4 are significantly upregulated after OIT (desensitized and tolerance) versus NT. Secreted proteins from allergen-specific B cells revealed higher amounts of regulatory cytokines, IL-10 and TGF-β after OIT and NT. Taken together, allergen-specific B cells are essential elements in regulating food allergen tolerance in both OIT-received and naturally-resolved individuals.

Author(s):  
Yaqiong Cui ◽  
Yang Yu ◽  
Shuxiang Lin ◽  
Li Xu ◽  
Liuxu Li ◽  
...  

<b><i>Background:</i></b> Cow’s milk allergy (CMA) is the most common IgE-mediated food allergy and Bos d 5 is the major allergen in cow’s milk proteins. More than 60% of the patients with CMA are sensitized to this protein. <b><i>Methods and Results:</i></b> A recombinant protein, encoded by a synthetic gene and consisting of reassembled Bos d 5 fragments, was expressed in <i>E. coli</i> strain BL21 (DE3) cells and purified to homogeneity. The B5M lacked relevant IgE-reactivity and allergenic activity compared with Bos d 5 in dot-blot and basophil activation assays. T-cell proliferation experiments demonstrated that B5M preserved the main T cell epitopes of Bos d 5. Immunization of rabbits with B5M induced protective IgG antibodies that blocked the binding of patients’ IgE antibodies to the wild-type allergen and inhibited the degranulation of basophils induced by Bos d 5. <b><i>Conclusion:</i></b> Thus, we developed a new strategy, which was based on rational molecular reassembly for allergen-specific immunotherapy (AIT) of CMA and food allergy.


Author(s):  
Lujing Tang ◽  
Yu Yu ◽  
Xiangyuan Pu ◽  
Jie Chen

Background: Cow’s milk allergy(CMA) is the most common allergy in infants that decreases the quality of life of patients and their families. Standard treatment for CMA is the strict avoidance of milk, new treatment strategies such as oral immunotherapy (OIT) have been sought for patients with CMA . We aimed to assess the clinical efficacy and safety of OIT in the treatment of children with IgE-mediated cow’s milk allergy (IMCMA). Methods: We searched all randomized controlled trials (RCTs) in which OIT is used to treat children with IMCMA from 5 international electronic databases. We estimated a pooled relative ratio (RR) for each outcome using a Mantel-Haenzel fixed-effect model if statistical heterogeneity was low. Results: Eleven studies were chosen for meta-analysis, including a total of 469 children (242 OIT, 227 control). 176 patients (72.7%) in the OIT were desensitized compared to 49 patients in the control group (RR 7.35, 95%CI 2.82-19.13, p<0.0001). The desensitization effect of OIT was particularly significant in children over 3 years old (RR 18.05, 95%CI 6.48-50.26, p<0.00001). Although adverse effects were common, they usually involved mild reactions, but epinephrine use was more common in the OIT group (RR 7.69, 95%CI 2.16-27.33, p<0.002). Conclusion: OIT can lead to desensitization in the majority of individuals with IMCMA, especially in patients over 3-years old. A major problem of OIT is the frequency of adverse events, although most are mild. OIT may be an alternative treatment in the future.


2020 ◽  
Author(s):  
Yoko Miura ◽  
Ken‐ichi Nagakura ◽  
Makoto Nishino ◽  
Mari Takei ◽  
Kyohei Takahashi ◽  
...  

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