Allergy, Asthma & Immunology Research最新文献

Lipids are important skin components that provide, together with proteins, barrier function of the skin. Keratinocyte terminal differentiation launches unique metabolic changes to lipid metabolism that result in the predominance of ceramides within lipids of the stratum corneum (SC)-the very top portion of the skin. Differentiating keratinocytes form unique ceramides that can be found only in the skin, and generate specialized extracellular structures known as lamellae. Lamellae establish tight hydrophobic layers between dying keratinocytes to protect the body from water loss and also from penetration of allergens and bacteria. Genetic and immunological factors may lead to the failure of keratinocyte terminal differentiation and significantly alter the proportion between SC components. The consequence of such changes is loss or deterioration of skin barrier function that can lead to pathological changes in the skin. This review summarizes our current understanding of the role of lipids in skin barrier function. It also draws attention to the utility of testing SC for lipid and protein biomarkers to predict future onset of allergic skin diseases.

Purpose: Chronic rhinosinusitis (CRS) is classified into type 2 (T2) and non-T2 inflammation. T2 CRS presents as a severe form, CRS with nasal polyps (CRSwNP), which often occurs with asthma as a comorbidity worldwide. Some cases of non-T2 CRS show nasal polyposis and refractoriness, mainly in Asian countries. However, its mechanism remains elusive. To investigate a biomarker for the refractoriness of non-T2 CRSwNP via RNA sequencing.

Methods: RNA sequencing by using nasal polyps (NPs) and ethmoidal mucosa (EM) from CRS subjects and uncinate tissues from controls was performed, and differentially expressed genes (DEGs) were analyzed (cutoffs: expression change > 2-fold, P < 0.01). Immunofluorescence staining and enzyme-linked immunosorbent assay were performed.

Results: We identified DEGs among T2-NP, non-T2-NP, T2-EM, non-T2-EM, and controls (NP vs. controls: 1,877 genes, EM vs. controls: 1,124 genes, T2-NP vs. controls: 1,790 genes, non-T2-NP vs. controls: 2,012 genes, T2-EM vs. controls: 740 genes, non-T2-EM vs. controls: 1,553 genes). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that neutrophil extracellular trap (NET) formation, systemic lupus erythematosus, and the phagosome were enriched in non-T2-NP vs. controls and non-T2-EM vs. controls. Immunofluorescence staining confirmed that NETs were elevated in non-T2-NP. Cytokine analysis demonstrated that NETs were significantly related to the refractoriness in non-T2-NPs.

Conclusions: This study demonstrated DEGs between T2 and non-T2 inflammation. These results suggest that NETs may contribute to the refractoriness in non-T2-NPs and have a promise as a therapeutic strategy for patients with refractory non-T2-NP.

Purpose: The constitutive photomorphogenesis 9 signalosome (CSN) is a highly conserved protein complex comprised of eight subunits, each of which play crucial roles in diverse cellular processes, such as signal transduction, gene transcription, angiogenesis, and cell proliferation. In the context of asthma, a potential emerging target is the programmed death-ligand 1 (PD-L1)-mediated pathway, which serves as a significant immune checkpoint inhibitor in this condition. However, the precise involvement of CSN subunit 5 (CSN5) in bronchial asthma and the interplay between CSN5 and PD-L1 in asthma remain poorly understood.

Methods: The potential association between CSN5 and bronchial asthma was explored in a mouse model of ovalbumin (OVA)-induced asthma. Samples were obtained from human lung microvascular endothelial cell (HMVEC-L) treated with Dermatophagoides pteronyssinus (Der p 1) and CSN5 small interfering RNA. The expression of nuclear factor (NF)-κB, IκBα, inhibitor of κB kinase β (IKKβ), PD-L1, and CSN5 was assessed. Additionally, plasma CSN5 levels in asthma patients, both in stable and exacerbated states, were examined.

Results: Plasma levels of CSN5 were elevated in patients with exacerbated asthma (n = 19) compared to both healthy controls (n = 10) and patients with stable asthma (n = 19). The CSN5 level demonstrated a correlation with lung function in individuals with asthma. Silencing CSN5 in HMVEC-L led to a reduction in NF-κB protein levels at 4 hours and PD-L1 levels at 4, 8, and 24 hours after Der p 1 treatment. In OVA-sensitized/challenged mice, goblet cell hyperplasia, lung fibrosis, and the levels of CSN5, PD-L1, interleukin-13, interferon-γ, phospho (p)-NF-κB, p-IκBα, and p-IKKβ proteins increased at 33 and 80 days compared to control mice. However, these changes were mitigated by treatment with a PD-L1 inhibitor.

Conclusions: These findings suggest that CSN5, along with PD-L1, could serve as a promising target for the treatment of asthma.

Purpose: Allergen exposure is the most potent factor in allergen sensitization, which affects the exacerbation and severity of allergic diseases. Due to industrialization and climate change, the pattern of allergen sensitization has changed over time, and the incidence of allergic diseases has also increased. This study investigated the status of allergen sensitization in the Korean population and its effects on allergic diseases.

Methods: A total of 2,386 participants aged ≥ 10 years, who underwent 7 specific immunoglobulin E tests for aeroallergens (Dermatophagoides farinae [Der f], dog dander, cat epithelium, birch, oak, Japanese hop, and ragweed), were selected among the participants of the 2019 Korean National Health and Nutrition Examination Survey. We compared the demographic characteristics, combined allergic diseases, and sinusitis symptoms between the atopic and non-atopic groups.

Results: The prevalence of allergen sensitization in the general Korean population was 45%, and Der f was the most frequent cause of sensitization (39.9%). The prevalence of sensitization to indoor allergens was highest among teenagers and those belonging to the 20- to 29-year age group (P < 0.001). In contrast, there was a high prevalence of sensitization to outdoor allergens among individuals belonging to the age group of 60-69 years. The prevalence of atopic dermatitis (odds ratio [OR], 2.559; 95% confidence interval [CI], 1.689-3.878), allergic rhinitis (OR, 3.075; 95% CI, 2.426-3.897), and otitis media (OR, 1.481; 95% CI, 1.092-2.007) significantly increased by allergen sensitization. Patients with allergen sensitization were more likely to experience the symptoms of rhinitis and sinusitis.

Conclusions: The study findings confirmed that allergen sensitization occurs in approximately half of the general Korean population and affects the prevalence and symptoms of allergic diseases. This suggests that active allergy tests and diagnosis of allergic diseases are necessary in Koreans.

Asthma is a chronic heterogeneous disease characterized by various symptoms and persistent airway inflammation, resulting in progressive lung function decline. Classifying asthma phenotypes/endotypes is crucial because the underlying mechanisms and long-term outcomes vary from patient to patient. Recent trials have identified several biomarkers for classifying asthma phenotypes/endotypes, and current treatments have been developed on the basis of these biomarkers. Conventional biomarkers, including immunoglobulin E, blood/sputum eosinophil counts, airway obstruction or reversibility, and fractional exhaled nitric oxide, are widely used to diagnose asthma. However, these markers have some limitations, necessitating the discovery of additional biomarkers. Therefore, this review summarizes recently suggested biomarkers for representing type 2-high (eosinophilic) vs. type 2-low (neutrophilic) asthma, non-steroidal anti-inflammatory drug-exacerbated respiratory disease, and severe asthma. Additionally, we discuss the potential benefits of these biomarkers in classifying specific phenotypes/endotypes and managing asthmatic patients.

Purpose: Wheezing in early life is most frequently caused by viral lower respiratory tract illnesses, constituting a significant disease burden in children. This study aimed to investigate the association of wheezing in early life with autoimmune diseases throughout childhood.

Methods: A population-matched retrospective cohort study was conducted in Korea between 2002 and 2017. The cohort comprised 34,959 children admitted with viral wheezing before 2 years of age and an equal number of the matched unexposed children born in 2002 and 2003. Exposed infants were defined as those hospitalized for bronchiolitis or bronchial asthma before the age of 2. Unexposed controls were matched by sex and birth year at a 1:1 ratio, using incidence density sampling. A Cox proportional hazard model controlled for multiple risk factors was employed.

Results: The median age at hospitalization for wheeze was 9 months (interquartile range, 5-15 months), and 63% of the exposed infants were male. Over the mean 15-year follow-up period, the incidence rate of autoimmune diseases was 74.0 and 62.2 per 10,000 person-years in the exposed and matched unexposed cohorts, respectively. The adjusted hazard ratio for any autoimmune disease in the exposed cohort was 1.15 (95% confidence interval, 1.09-1.23) in comparison with the unexposed cohort. The exposed cohort revealed an augmented risk for specific autoimmune diseases, including juvenile idiopathic arthritis, Kawasaki disease, Henoch-Schönlein purpura, psoriasis, idiopathic thrombocytopenic purpura, and immunoglobulin A nephropathy. Risks were heightened for children with multiple wheezing episodes or a persistent wheezing episode after the age of 2 years.

Conclusions: This research identifies associations between early-life wheeze and the development of autoimmune diseases in childhood. Understanding these relationships can aid in recognizing the underlying pathophysiology of early-life wheeze and childhood autoimmune diseases, contributing to management strategies for these conditions.

The diagnostic decision point can help diagnose food allergies while reducing the need for oral food challenge (OFC) tests. We performed a multicenter survey of children aged 0-7 years from January 1, 2018 to March 31, 2022. A total of 231 children were recruited from 18 institutions. Wheat allergy (WA) or non-wheat allergy (NWA) was determined on the basis of OFC results and symptoms. There were no differences in age, sex, family history of allergy or allergic comorbidities between the WA and NWA groups. According to receiver operating characteristic analysis for wheat-specific immunoglobulin E (IgE), the optimal cutoff value, positive decision point, and negative decision point were 10.2, 33.5, and 0.41 kU/L, respectively. For the ω-5 gliadin-specific IgE, their values were 0.69, 3.88, and 0.01 kU/L, respectively. This new diagnostic decision point may be used to diagnose WA in Korean children.

Prurigo nodularis (PN) is a chronic neuroinflammatory dermatosis with severe pruritus that has limited efficacy in various conventional treatments. This study investigated the outcomes of upadacitinib treatment in patients with refractory PN. A prospective study was conducted to screen for potential chronic infections prior to treatment. Upadacitinib was administered at a daily dose of 15 mg for 24 weeks, and the treatment response was assessed using the itch Numeric Rating Scale (NRS), investigator's Global Assessment (IGA), and Dermatology Life Quality Index (DLQI). Adverse events were monitored at each visit. Ten patients, with an average age of 48.8 years, were included in the study. All participants were treated with systemic cyclosporine before receiving upadacitinib, which yielded limited responses. At baseline, the mean prurigo severity scores assessed using the IGA, DLQI, and itch NRS were 3.4, 17.8, and 8.1, respectively; after 24 weeks of treatment, these scores significantly reduced to 1.0, 0.6, and 0.8, respectively. No severe adverse effects were observed. In conclusion, upadacitinib could be considered an alternative therapeutic option with good tolerability for refractory PN.

Purpose: Atopic march is defined as the development of atopic dermatitis in early childhood. We recently developed an atopic march mouse model through skin sensitization with aeroallergens from house dust mites and cockroaches. Using this model, this study aimed to evaluate the oral immunotherapy efficacy of Lactococcus lactis harboring specific antigens on the progression of atopic march.

Methods: Dust mite major allergen Der p 2 and cockroach Per a 2-372 were expressed in L. lactis as a fusion recombinant clone (D2P2). L. lactis-D2P2 was administered intragastrically to Aeroallergen patch-sensitized mice once a day for a total of 35 times. The immunological variables in sera, scratching behavior, airway hyperresponsiveness (AHR), and pathology of lungs and skin were evaluated.

Results: Our data showed that L. lactis-D2P2 significantly lowered total immunoglobulin E levels, decreased scratch bouts, and relieved AHR compared with the control mice. Histological analysis of the skin and lung tissue demonstrated the therapeutic effects of L. lactis-D2P2 to modulate immune responses via decreased eosinophil infiltration and reduced expression of key cytokines, interleukin (IL)-31 and IL-13, respectively.

Conclusions: The results imply that mucosal allergen-specific immunotherapy of L. lactis-D2P2 is a more cost-effective alternative to conventional subcutaneous allergen-specific immunotherapy. This study provides a promising platform for the development of novel oral protein-based vaccines in the early prevention of allergies.

Airway remodeling is a key characteristic of allergic asthma. Epithelial-mesenchymal transition (EMT) induced by various factors, particularly transforming growth factor (TGF)-β1, orchestrates airway remodeling. Protein phosphatase 2A (PP2A), an important serine-threonine phosphatase, is involved in TGF-β1 production and EMT. Long noncoding RNAs (lncRNAs) have emerged as novel players in regulating EMT. Here, we aimed to explore the effects and mechanisms of action of lincR-PPP2R5C, a lncRNA that affects PP2A activity, on airway remodeling in a mouse model of chronic allergic asthma. LincR-PPP2R5C knockout (KO) alleviated inflammatory responses in house dust mite (HDM)-induced chronic allergic asthma. Moreover, airway remodeling and EMT were reduced in lung tissues of lincR-PPP2R5C KO mice. HDM extract induced EMT in airway epithelial cells, which was decreased following lincR-PPP2R5C KO. Mechanistically, lincR-PPP2R5C deficiency enhanced PP2A activity, which inhibited TGF-β1 production in epithelial cells. In conclusion, lincR-PPP2R5C deficiency prevented HDM-induced airway remodeling in mice by reversing EMT, which was mediated by the PP2A/TGF-β1 signaling pathway. Thus, lncRNAs, i.e., lincR-PPP2R5C, may be potential targets to prevent airway remodeling in allergic asthma.