Yasuko Hatano

Predictive value of IgE/IgG4 antibody ratio in children with egg allergy

BackgroundThe aim of this study was to investigate the role of specific IgG4 antibodies to hen’s egg white and determine their utility as a marker for the outcome of oral challenge test in children sensitized to hen’s eggMethodsThe hen’s egg oral food challenge test was performed in 105 sensitized children without atopic dermatitis, and the titers of egg white-specific immunoglobulin G4 (IgG4) and immunoglobulin E (IgE) antibodies were measured. To set the cut-off values of IgG4, IgE, and the IgE/IgG4 ratio for predicting positive results in oral challenges, receiver operating characteristic curves were plotted and the area under the curves (AUC) were calculated.ResultsSixty-four of 105 oral challenges with whole eggs were assessed as positive. The AUC for IgE, IgG4, and IgE/IgG4 for the prediction of positive results were 0.609, 0.724, and 0.847, respectively. Thus, the IgE/IgG4 ratio generated significantly higher specificity, sensitivity, positive predictive value (%), and negative predictive value (%) than the individual IgE and IgG4. The negative predictive value of the IgE/IgG4 ratio was 90% at a value of 1.ConclusionsWe have demonstrated that the egg white-specific serum IgE/IgG4 ratio is important for predicting reactivity to egg during food challenges.

Phagocytosis of heat-killed Staphylococcus aureus by eosinophils: comparison with neutrophils.

Eosinophils are characterized by several functional properties, such as chemotaxis, adhesion, superoxide anion production, and degranulation. In this article, we have studied the role of bacterial ingestion by eosinophils in comparison with that by neutrophils. Eosinophils and neutrophils were purified by using the Percoll gradient method followed by selection with CD16‐coated immunomagnetic beads and centrifugation through a Ficoll‐Hypaque gradient combined with dextran sedimentation, respectively. Both cells were preincubated with anti‐FcγRIIa mAb (CD32 mAb), anti‐FcγRIIIb mAb (CD16 mAb), anti‐CR3 (CD11b mAb), or anti‐CR1 (CD35 mAb) before being examined for phagocytosis of opsonized heat‐killed Staphylococcus aureus (S. aureus). Phagocytosis and production of hydrogen peroxide were simultaneously measured by flow cytometry using S. aureus labeled with propidium iodide and stained with 2′,7′‐dichlorofluorescein diacetate. Eosinophils showed significantly lower activity than neutrophils in both phagocytosis and hydrogen peroxide production. Phagocytosis by both cells was decreased by heat‐inactivated serum. Phagocytosis by neutrophils was significantly inhibited by CD16 mAb and CD32 mAb, whereas that by eosinophils was only inhibited by CD35 mAb. Whereas the mechanism of phagocytosis by neutrophils was mediated by CD16 and CD32, that of eosinophils was modulated by complement receptor 1 (CD35).

Key for Successful Home-Based Slow Oral Immunotherapy in Children with Egg Allergy: Age and Sensitivity

Background: Oral immunotherapy (OIT) has been recognized as a promising therapy for children with food allergy. However a part of applied patients was not able to increase doses of allergic food. Since a clear standard for the appropriate patient selection for OIT has not been established, we tried to determine the indication criteria for when and/or to whom OIT should be applied. Method: We retrospectively reviewed the medical records of 82 children treated by home-based slow OIT which shows the administration of baked eggs orally every 2-3 days at home for two months as maintenance dose after open food challenge and statistically analyzed their clinical courses to identify the prognostic factors associated with a successful result. We applied the variables such as age, sex, symptoms during OIT, initial dose when starting OIT, specific IgE level and dislike of eggs, to a multivariate stepwise logistic regression analysis. Results: A total of 40 (56%) children reached remission in the OIT trial for a median of 213 days without severer allergic reactions, the remaining 31 (44%) could not reach the remission stage. We found the clinical course of the patients to be significantly associated with age and the initial dose of OIT. The children under 4 years of age or who could ingest larger portions (more than 1g if under 4 years, and 6g if over 5 years) as an initial dose were found to be the best candidates for OIT. Conclusions: This study revealed that home-based slow OIT caused almost successful results without severe allergic results in the children with egg allergy, and especially when starting before 5 years of age it is remarkable even if their initial doses were limited. This is the first report to contribute to the establishment of the indication criteria for home-based OIT.

Immunotherapy for cow's milk allergy

ABSTRACT Oral immunotherapy (OIT) is used regularly for young children with cows milk (CM) allergy and has been shown to be effective in several studies. However, adverse events occur frequently during OIT. Furthermore, there are only 5 randomized controlled trial studies of CM-OIT and these are low-powered single center trials. Therefore, evidence levels are also low and sometimes frequent and severe allergic events occur during the OIT. Furthermore, there are no standardized protocols in pediatric allergy guidelines from several countries and studies with long-term follow-up observations and clinical tolerance defined as sustained unresponsiveness are rare. Additionally, clinical tolerance by OIT is generally not well defined and obscure. Thus, several problems remain to be resolved, however we hope OIT in combination with omalizumab and less allergenic heated CM products will resolve these problems in the future.

Oral immunotherapy combined with omalizumab for high–risk cow’s milk allergy: a randomized controlled trial

We evaluated the efficacy and safety of oral immunotherapy (OIT) combined with 24 weeks of omalizumab (OMB) at inducing desensitization in children with cow’s milk allergy (CM) compared with an untreated group. The present study was a prospective randomized controlled trial. Sixteen patients (age, 6–14 years) with high IgE levels to CM were enrolled in the present study. Patients were randomized 1:1 to receive OMB-OIT group or untreated group. The primary outcome was the induction of desensitization at 8 weeks after OMB was discontinued in OMB-OIT treated group and at 32 weeks after study entry. None of the 6 children in the untreated group developed desensitization to CM while all of the 10 children in the OIT-OMB treated group achieved desensitization (P < 0.001). A significantly decreased wheal diameter in response to a skin prick test using CM was found in the OMB-OIT treated group (P < 0.05). These data suggest that OIT combined with OMB using microwave heated CM may help to induce desensitization for children with high-risk CM allergy. This prospective randomized controlled trial was intended for 50 participants but was prematurely discontinued due to overwhelming superiority of OMB combined with microwave heated OIT over CM avoidance.

Author Correction: Oral immunotherapy combined with omalizumab for high–risk cow’s milk allergy: a randomized controlled trial

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Correction: Predictive value of IgE/IgG4 antibody ratio in children with egg allergy

Following the publication of our article (Allergy, Asthma & Clinical Immunology 2012, 8:9) two separate errors within the manuscript have come to our attention. These errors can both be found in the Results section.