Efficacy and safety of sublingual immunotherapy using house dust mite tablet for 1-4 years old children with perennial allergic rhinitis.

BACKGROUND: Sublingual immunotherapy (SLIT) for perennial allergic rhinitis (AR) has not been extensively studied in preschoolers. We investigated the efficacy and safety of house dust mite (HDM) SLIT-tablet for children aged 1-4 years. METHODS: Children aged 1-4 years with AR were divided into SLIT (n = 22) and control (n = 12) groups based on their guardians' preferences. The SLIT group received a daily dose of 10,000 JAU of HDM SLIT-tablet for 12 months, whereas the control group received symptomatic treatment only. RESULTS: The baseline median age was 41 and 34 months in the SLIT and control groups, respectively, and the median AR symptom score was 4 for both groups. Compared with baseline, the AR symptom score had decreased significantly in the SLIT group after 12 months (score: 3, p = .002), whereas it tended to increase in the control group (score: 6, p = .08). Adverse reactions to SLIT were mild and occurred in eight patients (36%). In the SLIT group, Dermatophagoides (D.) farinae-specific IgE (sIgE) levels increased during the first 6 months and decreased to baseline levels at 12 months. In the control group, D. farinae-sIgE levels had increased significantly at 12 months compared to baseline (p = .01). D. farinae-specific IgG4 and HDM IgE-blocking factor levels were significantly increased at 12 months compared to baseline in the SLIT group only (p < .001). A lower wheezing frequency was seen in the SLIT group (0.3%) compared to the control group (0.7%). CONCLUSION: This pilot study demonstrated the efficacy, safety, and immunomodulatory effects of HDM SLIT-tablet in preschoolers with AR.

Practical N-to-C peptide synthesis with minimal protecting groups.

Accessible drug modalities have continued to increase in number in recent years. Peptides play a central role as pharmaceuticals and biomaterials in these new drug modalities. Although traditional peptide synthesis using chain-elongation from C- to N-terminus is reliable, it produces large quantities of chemical waste derived from protecting groups and condensation reagents, which place a heavy burden on the environment. Here we report an alternative N-to-C elongation strategy utilizing catalytic peptide thioacid formation and oxidative peptide bond formation with main chain-unprotected amino acids under aerobic conditions. This method is applicable to both iterative peptide couplings and convergent fragment couplings without requiring elaborate condensation reagents and protecting group manipulations. A recyclable N-hydroxy pyridone additive effectively suppresses epimerization at the elongating chain. We demonstrate the practicality of this method by showcasing a straightforward synthesis of the nonapeptide DSIP. This method further opens the door to clean and atom-efficient peptide synthesis.

Long-term outcomes of oral immunotherapy for anaphylactic egg allergy in children.

Background: Studies of long-term oral immunotherapy (OIT) in children with anaphylactic egg allergy are limited. Objective: Our aim was to investigate the long-term outcomes of OIT for anaphylactic egg allergy. Methods: The participants included children (aged ≥ 5 years) with a history of anaphylaxis in response to eggs and objective reactions to oral food challenge (OFC) with 250 mg of egg protein. In the OIT group, the home starting dose of egg protein set during 5 days of hospitalization was ingested once daily and gradually increased to 1000 mg. Over the next year, participants temporarily discontinued OIT for 2 weeks and underwent OFC with 3100 mg of egg protein annually until they passed. The historical control group comprised patients who did not receive OIT and repeated OFCs annually. Results: In the OIT group (n = 20), the baseline median egg white- and ovomucoid-specific IgE levels were 45.5 and 38.5 kUA/L, respectively. The rate of passing OFC with 3100 mg of egg protein gradually increased in the OIT group, with rates of 20% at 1 year, 35% at 2 years, and 55% at 3 years, which were significantly higher than the rates in the historical control group at 3 years (5% [P < .001]). In the OIT group, 5 anaphylaxis events (0.04%) occurred at home, and 1 participant required intramuscular adrenaline. Furthermore, egg white- and ovomucoid-specific IgE levels decreased significantly after 3 years in both groups, whereas in the OIT group, these specific IgG and IgG4 levels increased significantly after a year. Conclusion: Long-term OIT accelerated immunologic changes and enabled ingestion of 3100 mg of egg protein in half of the participants with anaphylactic egg allergy.

A catalytic one-step synthesis of peptide thioacids: the synthesis of leuprorelin via iterative peptide-fragment coupling reactions.

A catalytic one-step synthesis of peptide thioacids was developed. The oxygen-sulfur atom exchange reaction converted the carboxy group at the C-terminus of the peptides into a thiocarboxy group with suppressed epimerization. This method was successfully applied to the synthesis of the peptide drug leuprorelin via an iterative fragment-coupling protocol.