Allergology International最新文献

Background: Hypersensitivity pneumonitis (HP) is a complex and heterogenous interstitial lung disease (ILD) that occurs in susceptible individuals due to certain inhaled antigens. Fibrotic-HP is a major underlying disease of progressive pulmonary fibrosis. Therefore, in addition to the radiological features of HP, quantitatively measuring fibrosis is important to evaluate disease severity and progression. The present study aimed to compare three-dimensional computed tomography (3D-CT)-derived lung volumes (LVs) of patients with HP and determine its association with mortality risk.

Methods: In this retrospective and multicenter cohort study, 126 patients diagnosed with HP (fibrotic, n = 72 and non-fibrotic, n = 54) with a confidence level higher than moderate were enrolled. Each lobe LV was measured using 3D-CT at the time of diagnosis and standardized using predicted forced vital capacity. The 3D-CT LV was compared with those of 42 controls and 140 patients with idiopathic pulmonary fibrosis (IPF).

Results: Compared to patients with fibrotic-HP, the standardized total LV was significantly higher in controls and patients with non-fibrotic-HP and was similar in patients with IPF. Longitudinal analyses demonstrated that approximately half of the patients with fibrotic-HP had an annual decrease in total LV. Decreased total and lower-lobe LVs were associated with shorter survival, and were independently associated with mortality together with ongoing exposure to inciting antigens. A composite model consisting of ongoing exposure to inciting antigens and total or lower-lobe LV successfully classified mortality risk into three groups.

Conclusions: Quantitatively measuring standardized LV can help determine disease severity, progression, and mortality risk in patients with fibrotic-HP.

Background: In many countries, neuro-muscular blocking agents (NMBAs) are the first cause of perioperative anaphylaxis. Epidemiological studies identified pholcodine, a quaternary ammonium-containing opiate as one of the sensitization sources. However, NMBA anaphylaxis exists in countries where pholcodine was unavailable, prompting the hypothesis of other sensitizing molecules, most likely quaternary ammonium compounds (QACs). Indeed, QACs are commonly used as disinfectants, antiseptics, preservatives, and detergents. Occupational exposure to QACs has been reported as a risk factor for NMBA anaphylaxis, but little is known about the sensitization mechanism and the capacity of these molecules to elicit an immune response. We aimed to establish the immunogenicity of QACs representative of the main existing chemical structures.

Methods: We measured the sensitization potential of seven QACs (two polyquaterniums, three alkyl-ammoniums and two aromatic ammoniums) by using two standard dendritic cells (DCs) models (THP-1 cell line and monocyte derived-dendritic cells). The allergenicity of the sensitizing compounds was further tested in heterologous and autologous T-cell-DC co-culture models.

Results: Amongst the seven molecules tested, four could modulate activation markers on DCs, and thus can be classified as chemical sensitizers (polyquaterniums-7 and -10, ethylhexadecyldimethylammonium and benzethonium). This activation was accompanied by the secretion of pro-inflammatory and maturation cytokines. Furthermore, activation by polyquaternium-7 could induce T-cell proliferation in heterologous and autologous coculture models, demonstrating that this molecule can induce a specific CD4⁺ T cell response.

Conclusions: We provide evidence at the cellular level that some QACs can elicit an immune response, which could be in line with the hypothesis of these molecules' role in NMBA sensitization.

Background: Skin reaction patterns vary across patients with cholinergic urticaria (CholU), but their definition, prevalence, and clinical significance remain ill characterized.

Methods: Patients with CholU underwent pulse-controlled ergometry provocation testing to analyze skin reaction patterns and their correlation with location, onset, severity, sweating behaviour, clinical features, disease control, and quality of life (QoL) impairment.

Results: Based on the size, color, spacing, and shape of wheals as well as their surrounding skin responses, we identified six distinct types of CholU skin reactions, which differed in prevalence, from 83% (Type I) to 11% (Type VI) of patients affected. Almost all patients (94%) had ≥1 type of skin reaction pattern. Sweating was reduced in the majority of CholU patients and most prominently reduced in patients with Type VI skin signs (very small, round, red, widely spaced wheals with surrounding anemic halo), which emerged exclusively on the extremities. Type V skin signs (large, irregular, anemic, widely spaced wheals with moderate size erythema) were associated with the most severe clinical presentation and poorest QoL.

Conclusions: Our analysis showed that most patients have more than one type of skin reaction patterns and that different skin signs are linked to distinct features. Future studies should determine any links between treatment response and types of skin signs in CholU.

Allergen-specific IgE is a major mediator of allergic responses and contributes greatly to allergic disease in the human population. Therapies that inhibit the production of IgE would be useful for lessening the burden of allergic disease. A great deal of research has focused on how IgE responses are regulated, and several factors that promote the production of allergic IgE have been characterized. T follicular helper (TFH) cells expressing IL-4 are required for the development of IgE expressing B cells in the germinal center (GC). Ig somatic hypermutation and B cell selection in the GC leads to the development of high affinity allergen-specific IgE that promotes anaphylaxis, a severe form of allergic response. T follicular regulatory (TFR) cells are also found in the GC response and act with TFH cells in the selection of high affinity IgE + B cells. This review examines the current literature on IgE responses and TFR cells. In mouse studies, TFR cells have a suppressive role on IgE responses in allergic airway disease, however TFR cells also play a helper role in the IgE response in food allergy. In human studies, TFR cells correlate with a decreased allergic response but evidence for a direct suppressive role of TFR cells on IgE in vivo is lacking. TFR cells may represent a new target for allergy therapies, but caution must be exercised to promote the suppressor activity of TFR cells and not the helper activity of TFR cells on IgE responses.

Food allergies are an increasing global problem and societal issue. In addition to the potential for severe allergic reactions from accidental ingestion, food allergies impose a significant burden on the quality of life, nutrition, cost of living, and social activities of both those afflicted and their caregivers. Strict avoidance of allergens and use of emergency medications to treat allergic reactions are the traditional management and treatment strategies; however, significant progress has been made in recent years toward better treatment of food allergies. Many clinical trials on food allergen immunotherapy (oral, epicutaneous, and sublingual) have revealed its efficacy in increasing reaction thresholds and desensitization. These positive results led to the first FDA approval of peanut oral immunotherapy (OIT). However, safer and more effective approaches are required, and adjunct treatments and allergen modifications are being considered. More than 100 facilities in Japan conduct OIT, and numerous studies on it have been reported. Unlike in Europe and the US, stepwise oral food challenges with dietary guidance are conducted separately from the OIT. This review describes the current perspectives on allergen immunotherapy for the treatment of food allergies, focusing on evidence from Japan.

Background: Epidemiological studies have identified associations between gastroesophageal reflux (GER) and cow's milk allergy (CMA) in infants. However, the role of GER in the development of CMA remains poorly understood. Our primary objectives were to develop a mouse model that suggests GER as a potential pathogenic mechanism for CMA and to elucidate the immunological mechanisms that connect lung innate immunity with CMA.

Methods: Mice were exposed to cow's milk (CM) treated with hydrochloric acid through repeated aspiration into their airways. Subsequently, they were challenged by intraperitoneal injection of CM extract. The immunological mechanisms were investigated using comprehensive single-cell RNA sequencing (scRNA-seq) analysis of the lungs, combined with the use of genetically modified mice.

Results: Mice exposed to CM mixed with hydrochloric acid via airway sensitization developed CMA, as evidenced by the production of antigen-specific IgE and IgG antibodies, and the induction of anaphylaxis upon systemic antigen administration. In contrast, aspiration of CM alone did not induce CMA. scRNA-seq analysis revealed potential roles of alveolar macrophages in response to hydrochloric acid. Mice lacking the TLR4 pathway were protected from developing CMA.

Conclusions: We have developed a novel mouse model for CMA that utilizes the natural antigen and follows the physiological airway sensitization pathway, thus potentially resembling clinical scenarios. This model, named the acidified milk aspiration-induced allergy model, has the potential to shed light on the role of early innate immunity by analyzing a more physiological model.

Human T follicular helper (Tfh) cells play a crucial role in orchestrating B cell differentiation, maturation, and immunoglobulin class switching. Recent studies have underscored the presence of Bcl-6 + Tfh cells not only in secondary lymphoid organs but also within tertiary lymphoid structures at inflammatory sites, emphasizing their pivotal role in disease pathogenesis. Furthermore, Tfh cells have been found to transit between lesion sites, lymph nodes, and peripheral blood, as revealed by T cell receptor repertoire analysis. Among Tfh subsets, Tfh2 cells have emerged as central orchestrators in driving the production of IgE and IgG4 from B cells. Their critical role in diseases such as allergy, malignancy, and IgG4-related disease highlights their profound impact on balancing inflammation and immune tolerance. Our current review provides the molecular characteristics of human Tfh cells, the differentiation pathways of Tfh subsets, mechanisms by which Tfh subsets induce IgE and IgG4 production, and their clinical implications in allergy, malignancy, and IgG4-related disease.

Background: Solubility is a common feature of allergens. However, the causative relationship between this protein-intrinsic feature and sensitization capacity of allergens is not fully understood. This study aimed to proof the concept of solubility as a protein intrinsic feature of allergens.

Methods: The soluble birch pollen allergen Bet v 1 was covalently coupled to 1 μm silica particles. IgE-binding and -cross-linking capacity was assessed by inhibition ELISA and mediator release assay, respectively. Alterations in adjuvanticity by particle-loading were investigated by activation of dendritic cells, mast cells and the Toll-like receptor 4 pathway as well as by Th2 polarization in an IL-4 reporter mouse model. In BALB/c mice, particle-loaded and soluble Bet v 1 were compared in a model of allergic sensitization. Antigen uptake and presentation was analysed by restimulating human Bet v 1-specific T cell lines.

Results: Covalent coupling of Bet v 1 to silica particles resulted in an insoluble antigen with retained IgE-binding and -cross-linking capacity and no increase in adjuvanticity. In vivo, particle-loaded Bet v 1 induced significantly lower Bet v 1-specific (s)IgE, whereas sIgG1 and sIgG2a levels remained unaffected. The ratio of Th2 to Th1 cells was significantly lower in mice sensitized with particle-loaded Bet v 1. Particle-loading of Bet v 1 resulted in a 24-fold higher T cell activation capacity in Bet v 1-specific T cell lines, indicating more efficient uptake and presentation than of soluble Bet v 1.

Conclusions: Our results show that solubility is a decisive factor contributing to the sensitization capacity of allergens. The reduction in sensitization capacity of insoluble, particle-loaded antigens results from enhanced antigen uptake and presentation compared to soluble allergens.

Background: Artificial intelligence (AI) is a promising new technology that has the potential of diagnosing allergic conjunctival diseases (ACDs). However, its development is slowed by the absence of a tailored image database and explainable AI models. Thus, the purpose of this study was to develop an explainable AI model that can not only diagnose ACDs but also present the basis for the diagnosis.

Methods: A dataset of 4942 slit-lamp images from 10 ophthalmological institutions across Japan were used as the image database. A sequential pipeline of segmentation AI was constructed to identify 12 clinical findings in 1038 images of seasonal and perennial allergic conjunctivitis (AC), atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC), giant papillary conjunctivitis (GPC), and normal subjects. The performance of the pipeline was evaluated by determining its ability to obtain explainable results through the extraction of the findings. Its diagnostic accuracy was determined for 4 severity-based diagnosis classification of AC, AKC/VKC, GPC, and normal.

Results: Segmentation AI pipeline efficiently extracted crucial ACD indicators including conjunctival hyperemia, giant papillae, and shield ulcer, and offered interpretable insights. The AI pipeline diagnosis had a high diagnostic accuracy of 86.2%, and that of the board-certified ophthalmologists was 60.0%. The pipeline had a high classification performance, and the area under the curve (AUC) was 0.959 for AC, 0.905 for normal subjects, 0.847 for GPC, 0.829 for VKC, and 0.790 for AKC.

Conclusions: An explainable AI model created by a comprehensive image database can be used for diagnosing ACDs with high degree of accuracy.