A retrospective study of SARS-CoV-2 antibodies in children with allergies.

BACKGROUND: The dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children are continually changing. We conducted a survey of pediatric allergy patients attending our department to determine the prevalence of antibodies against SARS-CoV-2 in children. METHODS: A retrospective study was performed among children aged <11 years, referred to a pediatric allergy department between February 2020 and January 2022 with a chief complaint of allergy. The data of children with blood examination findings were retrospectively studied. Qualitative testing for anti-SARS-CoV-2 IgG and IgM antibodies was performed using a SARS-CoV-2 rapid antibody test. Participants were retested 1 year later to evaluate changes in antibody levels. RESULTS: In total, 310 patients with a median age of 26 months (interquartile range: 11.6-58.4 months) and male/female ratio of 1.31 were included. A total of 32 patients tested positive for anti-SARS-CoV-2 IgG or IgM antibodies. No differences were observed in the severity of allergic disease. The prevalence of antibodies was higher among children enrolled in preschool or school (odds ratio: 13.19, 95% confidence interval; 2.30-249.7). A total of 66.7% of patients underwent follow-up testing. The antibody positivity rate increased between the first and second testing, but this was not related to the number of medical visits or the severity of allergic disease. CONCLUSION: Antibody prevalence in children was low but increased during the study period. The majority of children who tested positive for SARS-CoV-2 antibodies did not have a history of coronavirus disease 2019, suggesting that most infections were subclinical.

Evidence of off-label inhalation therapy on pediatric asthma practice in Japan.

BACKGROUND: In Japan, many asthma inhalers do not have formal approval for use in the pediatric population because of the lack of domestic data. In real-world settings, however, numerous off-label medications are prescribed. Currently, the nature of off-label prescriptions of asthma inhalers on pediatric patients in Japan remains unclear. METHODS: Using public open-source national medical claims data, we investigated the real-world descriptive epidemiology of off-label prescriptions for asthma inhalers for pediatric patients. We obtained the number of off-label prescriptions of formulations for patients aged 0-14 years from anonymously summarized prescription data for a 7-year period starting from April 2014. The actual prescription numbers and their chronology over time were then analyzed. RESULTS: In 2019, 143,439 asthma inhalers were used off label in children and adolescents. Overall, 96.1% were inhaled corticosteroids (ICSs) or long-acting beta stimulants (LABAs), and 3.9% were high-dose ICS. Of ICSs and LABAs, 18.8% were off-label prescriptions. The total number of off-label ICS/LABA prescriptions and their percentage relative to the overall formulations gradually decreased but a notable disparity was observed among inhaler types. CONCLUSIONS: There was a surprisingly large number of off-label prescriptions of asthma inhalers in the pediatric population in Japan. The proper use of ICSs/LABAs and expansion of insurance coverage should be advocated to reduce off-label use.

Pharmacologic inhibition of Notch signaling suppresses food antigen-induced mucosal mast cell hyperplasia.

BACKGROUND: Mucosal mast cells (MMCs) play a central role in the development of symptoms associated with IgE-mediated food allergy. Recently, Notch2-mediated signaling was shown to be involved in proper MMC distribution in the intestinal tract. OBJECTIVE: This study aimed to clarify the mechanism by which Notch signaling regulates MMC distribution in the intestinal mucosa. Furthermore, pharmacologic inhibition of Notch signaling was evaluated as a treatment for symptoms associated with experimental food allergy. METHODS: Bone marrow-derived mast cells generated from mice were cultured with Notch ligands, and then expression of genes associated with MMCs was measured in the cells. In addition, the effect of an inhibitor of Notch signaling on food antigen-induced allergic reactions was examined in a mouse model of food allergy. RESULTS: Notch signaling induced MMC differentiation through upregulation of expression of genes characteristic of MMCs in the presence of IL-3. Some lamina propria cells isolated from the mouse small intestine expressed Notch ligands and were able to upregulate MMC markers in bone marrow-derived mast cells through Notch signaling. In a mouse model of food allergy, administration of a Notch signaling inhibitor led to suppression of food antigen-induced hyperplasia of intestinal MMCs, resulting in alleviation of allergic diarrhea and systemic anaphylaxis. CONCLUSION: Notch signaling contributes to differentiation and accumulation of MMCs in the intestinal mucosa. Thus inhibition of Notch signaling alleviates symptoms associated with experimental food allergy. These results raise the possibility that Notch signaling in mast cells is a novel target for therapy in patients with food allergy.

Eosinophilic gastroenteritis in a patient with Bruton's tyrosine kinase deficiency.

Eosinophilic gastrointestinal diseases (EGID) are relatively rare diseases characterized by eosinophilic infiltration of the gastrointestinal tract resulting in various gastrointestinal symptoms. EGID are often caused by allergic reactions or systemic eosinophilic disorders, but their comorbidity with Bruton's tyrosine kinase (BTK) deficiency has not been previously documented. Here, we report a case of eosinophilic gastroenteritis (EG) in a patient with BTK deficiency. Despite adequate replacement immunoglobulin (Ig) therapy, trough serum IgG was not maintained. To identify the underlying cause of the low trough level and chronic diarrhea, the intestine was investigated on endoscopy. We also screened for the variable number of tandem repeat polymorphism in FCGRT. Genetic analysis could not explain the low trough IgG, but endoscopy indicated eosinophilic enterocolitis. EG may be an important differential diagnosis when primary immunodeficiency patients have chronic diarrhea or continued low serum IgG.

The Transcription Factor Ehf Is Involved in TGF-ß-Induced Suppression of FcεRI and c-Kit Expression and FcεRI-Mediated Activation in Mast Cells.

FcεRI, which is composed of α, ß, and γ subunits, plays an important role in IgE-mediated allergic responses. TGF-ß1 has been reported to suppress FcεRI and stem cell factor receptor c-Kit expression on mast cell surfaces and to suppress mast cell activation induced by cross-linking of FcεRI. However, the molecular mechanism by which these expressions and activation are suppressed by TGF-ß1 remains unclear. In this study, we found that the expression of Ets homologous factor (Ehf), a member of the Ets family transcriptional factors, is upregulated by TGF-ß/Smad signaling in mouse bone marrow-derived mast cells (BMMCs). Forced expression of Ehf in BMMCs repressed the transcription of genes encoding FcεRIα, FcεRIß, and c-Kit, resulting in a reduction in cell surface FcεRI and c-Kit expression. Additionally, forced expression of Ehf suppressed FcεRI-mediated degranulation and cytokine production. Ehf inhibited the promoter activity of genes encoding FcεRIα, FcεRIß, and c-Kit by binding to these gene promoters. Furthermore, the mRNA levels of Gata1, Gata2, and Stat5b were lower in BMMCs stably expressing Ehf compared with control cells. Because GATA-1 and GATA-2 are positive regulators of FcεRI and c-Kit expression, decreased expression of GATAs may be also involved in the reduction of FcεRI and c-Kit expression. Decreased expression of Stat5 may contribute to the suppression of cytokine production by BMMCs. In part, mast cell response to TGF-ß1 was mimicked by forced expression of Ehf, suggesting that TGF-ß1 suppresses FcεRI and c-Kit expression and suppresses FcεRI-mediated activation through upregulation of Ehf.