Allergology International最新文献

In 2004, we started the initial attempt to evaluate the efficacy of SLIT for Japanese cedar pollinosis (JCP) using Japanese cedar (JC) pollen extract solution through a multicenter, placebo-controlled, double-blind comparative study. Based on its success in demonstrating the substantial efficacy of SLIT, we next conducted a larger-scale study by administering JC pollen to all JCP patients recruited. It was because of aiming to ascertain the effectiveness and safety of SLIT and its underlying mechanisms by comparing high- and non-responder patients. Despite limitations posed by liquid medication, significant effectiveness and safety demonstrated by the 2-year treatment served as the foundation for launching the first SLIT medicine for JCP, in 2014. Furthermore, in addition to the clearer Th1/Th2-imbalanced property in the high-responders, the possible involvement of bitter taste receptors in CD4⁺ T cells, apoptosis pathways in CD4⁺ T cells and basophils, and inducing a mast cell degranulation inhibitory molecule in the effect of SLIT was demonstrated. To solve the limitations posed by liquid medication, clinical trials evaluating JC pollen sublingual tablets started in 2014. Due to the minimal side effects, ease of administration, and convenient storage, the sublingual tablet medicine was launched in 2018. Giving the ongoing rise in demand for SLIT and considering that more than 1% of JCP patients are currently undergoing SLIT, the practical use of this treatment for multiple allergens is becoming increasingly important.

Background: Allergic asthma is largely dominated by Th2 lymphocytes. Micropeptides in Th2 cells and asthma remain unmasked. Here, we aimed to demonstrate a micropeptide, T-cell regulatory micropeptide (TREMP), in Th2 cell differentiation in asthma.

Methods: TREMP translated from lincR-PPP2R5C was validated using Western blotting and mass spectrometry. TREMP knockout mice were generated using CRISPR/Cas9. Coimmunoprecipitation revealed that TREMP targeted pyrroline-5-carboxylate reductase 1 (PYCR1), which was further explored in vitro and in vivo. The levels of TREMP and PYCR1 in Th2 cells from clinical samples were determined by flow cytometry.

Results: TREMP, encoded by lincR-PPP2R5C, was in the mitochondrion. The lentivirus encoding TREMP promoted Th2 cell differentiation. In contrast, Th2 differentiation was suppressed in TREMP^-/- CD4⁺ T cells. In the HDM-induced model of allergic airway inflammation, TREMP was increased in pulmonary tissues. Allergic airway inflammation was relieved in TREMP^-/- mice treated with HDM. Mechanistically, TREMP interacted with PYCR1, which regulated Th2 differentiation via glycolysis. Glycolysis was decreased in Th2 cells from TREMP^-/- mice and PYCR1^-/- mice. Similar to TREMP^-/- mice, allergic airway inflammation was mitigated in HDM-challenged PYCR1^-/- mice. Moreover, we measured TREMP and PYCR1 in asthma patients. And we found that, compared with those in healthy controls, the levels of TREMP and PYCR1 in Th2 cells were significantly increased in asthmatic patients.

Conclusions: The micropeptide TREMP encoded by lincR-PPP2R5C promoted Th2 differentiation in allergic airway inflammation by interacting with PYCR1 and enhancing glycolysis. Our findings highlight the importance of neglected micropeptides from noncoding RNAs in allergic diseases.

Background: Despite clinical implications, the pathogenesis of mucus plugging in asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) remains unclear. We hypothesized that distinct airway microbiomes might affect mucus plugging differently among ACO, asthma, and COPD and among different extents of airway eosinophilic inflammation.

Methods: The sputum microbiome, sputum cell differential count, and mucus plug score on computed tomography were cross-sectionally evaluated in patients with chronic airflow limitation.

Results: Patients with ACO, asthma, or COPD were enrolled (n = 56, 10, and 25). Higher mucus plug scores were associated with a greater relative abundance of the phylum Proteobacteria (rho = 0.29) only in patients with ACO and a greater relative abundance of the phylum Actinobacteria (rho = 0.46) only in patients with COPD. In multivariable models including only patients with ACO, the presence of mucus plugs was associated with a greater relative abundance of the phylum Proteobacteria and the genus Haemophilus, independent of smoking status, airflow limitation, and emphysema severity. Moreover, the mucus score was associated with a greater relative abundance of the genus Streptococcus (rho = 0.46) in patients with a high sputum eosinophil count (n = 22) and with that of the genus Haemophilus (rho = 0.46) in those with a moderate sputum eosinophil count (n = 26).

Conclusions: The associations between mucus plugging and the microbiome in ACO differed from those in COPD and asthma. Greater relative abundances of the phylum Proteobacteria and genus Haemophilus may be involved in mucus plugging in patients with ACO and moderate airway eosinophilic inflammation.

Allergen immunotherapy (AIT), including SCIT and SLIT, is a treatment that involves the administration of allergens to which patients with allergic diseases have been sensitized. HDM-SCIT for asthma is indicated in cases of HDM-sensitized allergic asthma with normal lung function. HDM-SCIT improves asthma symptoms and AHR, and decreases the medication dose. Importantly, AIT can improve other allergic diseases complicated by asthma, such as allergic rhinitis, which can also contribute to the improvement of asthma symptoms. Several studies have suggested that HDM-SLIT also attenuates the risk of asthma exacerbations, and improves lung function in asthma cases with allergic rhinitis. Furthermore, AIT can modify the natural course of allergic diseases, including asthma. For example, the effects of AIT are maintained for at least several years after treatment discontinuation. AIT can prevent the onset of asthma when introduced in allergic rhinitis, and can also inhibit or reduce new allergen sensitizations. Recent data have suggested that AIT may suppress non-targeted allergen-induced immune responses in addition to targeted allergen-induced responses, and suppress infections of the lower respiratory tract by enhancing IFN responses.

Background: To avoid complete elimination of hen eggs (HE) from diet, we introduced a very-low-dose (VLD) oral food challenge (OFC) in patients with severe HE allergy in 2019. Herein, we investigated the efficacy of VLD HE OFC for achieving the full dose OFC.

Methods: Patients with an overt allergic reaction to LD (1/32 HE [≤100 mg]) or less, egg white (EW) protein within 6 months were included. In the VLD group, patients not achieving full-dose OFC (1/2 HE: 1600 mg EW protein) within 2 years were excluded. We retrospectively compared the rate of passing a full-dose OFC between patients who underwent a LD OFC before 2019 (LD group) and those who underwent a VLD OFC (1/100 HE: 32 mg EW protein) after 2019 (VLD group). The period for passing the full-dose OFC was evaluated using Kaplan-Meier survival analysis.

Results: We enrolled 411 and 111 patients in the LD and VLD groups, respectively. The median age at OFC initiation was 2.2 [1.5-3.6] and 2.1 [1.4-3.2] years in the LD and VLD groups, respectively. EW- and ovomucoid-specific IgE levels were 38.3 (12.5-72.9) and 21.0 (8.3-46.2) kU_A/L in the LD group and 49.8 [18.8-83.9] and 32.1 [15.6-67.8] kU_A/L in the VLD group, respectively. Over 4 years, the LD and VLD groups passed the full-dose OFC at rates of 70 and 95%, respectively, with significant differences (log-rank test, P < 0.001).

Conclusions: VLD HE OFC may contribute to passing a full-dose OFC in patients with severe HE allergies.

Background: Food protein-induced enterocolitis syndrome caused by solid foods (Solid-FPIES) is a non-immunoglobulin E-mediated allergic disease characterized by delayed gastrointestinal symptoms. An oral food challenge (OFC) test, although necessary, can be inconclusive in cases with mild symptoms. Moreover, limited diagnostic marker availability highlights the need for novel surrogate markers. We aimed to examine the efficacy of fecal hemoglobin (FHb), lactoferrin (FLf), and calprotectin (FCp) over time in evaluating gastrointestinal inflammation degree in Solid-FPIES.

Methods: This observational study included 40 patients and 42 episodes at Juntendo University Hospital and affiliated hospitals between October 2020 and March 2024 categorized into FPIES (12 patients with 11 egg yolk, 1 fish, and 1 soybean episodes), control (14 patients with 15 episodes), and remission (14 patients). Fecal tests were performed for 7 days following antigen exposure. The ratios of each value were divided by the baseline value and analyzed over time course.

Results: The FPIES group had significantly higher peak ratios of all fecal markers than the control group (p < 0.01). The median FHb, FLf, and FCp ratios were 3.25, 9.09, and 9.79 in the FPIES group and 1.08, 1.29, and 1.49 in the control group, respectively. In the remission group, several patients had fluctuating fecal markers despite negative OFC, and one patient was diagnosed with FPIES by OFC with increased load. Receiver operating characteristic curve analyses revealed high diagnostic performance for each fecal marker in FPIES.

Conclusions: Sequential fecal marker examination proved valuable in diagnosing Solid-FPIES and evaluating the degree of gastrointestinal inflammation.