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Mast cells, mediators, and symptomatic activation

<abstract> <p>Mast cells (MC) are central effectors of allergic disease and distinct subsets with varying amounts of tryptase, chymase, and carboxypeptidase A3, and cathepsin G is distributed throughout the body. Their involvement in a diverse range of non-allergic illnesses mediated by a complex range of preformed and newly synthesized mediators is now increasingly recognized. The latter especially include conditions under the umbrella term of mast cell activation syndrome. In allergic disease, much has been written about the mechanisms by which the early and rapidly acting mediators produce both localized and systemic allergic symptoms. The role of chymase is presently underappreciated but there is increased awareness that MCs contain significant amounts of preformed TNF alpha and synthesize and releases a wide range of inflammatory cytokines such as interleukins (IL) 1β, IL6, IL31, and IL33. These can aggravate itching and perpetuate inflammation and likely contribute to the late constitutional symptoms seen in allergic reactions. Importantly, their involvement helps to clarify the role of MCs in stress and non-parasitic infections. Presently, unexplained is the increasing incidence of significant acute allergic reactions within a relatively short time frame. In this context, there is increasing interest in the environmental, menstrual, endocrine, circadian, and psychological factors that influence MC activation as well as the endocrine pathways involving the renin angiotensin system that oppose hypotension. In non-allergic diseases with normal numbers of MCs, reduced thresholds for activation may be produced by various combinations of life and dietary factors. Diagnosing these conditions is difficult but may be helped by urinary analysis of prostaglandin metabolites. The investigation and management of mastocytosis with and without mutations of c-kit is also relevant to allergic disease and the new medications used may also be helpful in idiopathic anaphylaxis. This knowledge may open a new chapter in human diseases and mast cell regulation.</p> </abstract>

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Exploring immune response and lab markers across COVID-19 severity levels

<p>This retrospective cohort study investigated antigen-specific antibody responses to SARS-CoV-2 and laboratory markers in coronavirus disease 2019 (COVID-19) patients of varying severities. Serum or plasma samples collected early in the pandemic were analyzed for the presence of IgG antibodies and IgG subclasses which target the recombinant spike (S) and nucleocapsid (N) proteins of SARS-CoV-2. Correlation analyses were conducted to assess the possible relationship between the IgG subclasses to SARS-CoV-2 proteins, inflammatory markers, and the severity of the disease. It was shown that the severity of the disease positively correlated with the C-reactive protein (CRP), but most of all with the neutrophil/lymphocyte ratio (NLR) levels. IgG titers against the S- and N-proteins decreased in the most severe COVID-19 cases, which potentially attributed to a delayed IgG formation compared to milder infections. The presence of anti-spike IgG displayed a medium negative correlation trend (not statistically significant, which might be due to the small sample size in our study) with laboratory markers (such as CRP, Fibrinogen, Degree) which are suggestive of infection severity. anti-S IgG correlated positively but weakly with the serum histamine levels. The presence of anti-N IgG at the time of hospitalization correlated with the subsequent outcome. At the same time, anti-N IgG1 correlated with the detection of the viral RNA in the blood. Thus, seroconversion may occur later in patients with a more severe pneumonia. The summary data suggests correlations between the expression of inflammatory markers and the antibody responses, which can also serve as early clinical markers.</p>

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<abstract> <p>Exposure to laboratory animal allergens has been a significant cause of IgE-mediated allergic symptoms and occupational asthma (OA). Mice are the predominant species used in medical and scientific facilities. We have previously published a review of our air monitoring data of mouse and rat major allergens (mus m 1 and rat n 1) expressible in ng·m<sup>−3</sup> from 2005–2016. We have now reassessed all this largely United Kingdom (UK) air monitoring data from 2005–2022, which include 77% and 47% additional mouse and rat results, respectively. Where possible, we have categorized the results to specific tasks and areas to identify those associated with higher exposures and explored temporal trends in exposure together with an estimation of the annual incidence of OA in 2005 and 2018. A downward shift in mouse results for personal samples was apparent from 2014, with evidence of a decrease in the 90<sup>th</sup> percentile, but both personal and static rat samples confoundingly showed an apparent increase from 2017. Activities of “cage changing”, “cage cleaning”, and “cage washing, dirty side” suggested substantial personal exposures in some facilities, while “bedding dumping” and “cage scraping” suggested generally high exposures, albeit modified by any respiratory protective equipment worn. Individually ventilated cages reduce exposure, but filter changing/cleaning can still lead to high exposures. Exposure from experimental and husbandry duties were generally lower, but in some facilities activities where animals are handled outside of cages can cause significant exposures. The reduction in personal exposure to the predominant species is consistent with an estimated 55% decrease in the UK annual incidence rate of OA in 2018 from 2005. The data may help facilities to improve exposure control by identifying higher risk activities, benchmarking their own monitoring data and help further reduce the risk of sensitization and subsequent allergic respiratory ill-health.</p> </abstract>

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Inhalation allergen sensitization patterns in children with allergic rhinitis and asthma

<sec><title>Objective</title><p>To investigate the differences in sensitization status and patterns of inhaled allergens in children with allergic rhinitis, cough allergic asthma, and bronchial asthma, to avoid allergens, and to explore the relationship between the sensitization status and patterns of inhaled allergens in allergic rhinitis and asthma.</p></sec><sec><title>Method</title><p>A retrospective evaluation was conducted on 1028 children with allergic rhinitis and asthma who underwent allergen specific IgE antibody testing at Xiamen University Affiliated Women's and Children's Hospital from 2022 to 2024. Based on basic medical information and clinical results, they were divided into allergic rhinitis group, cough allergic asthma group, and bronchial asthma group.</p></sec><sec><title>Results</title><p>The most common inhaled allergen detected in this study was house dust mite, followed by house dust and mold. The positive frequency of most inhaled allergens in the bronchial asthma group was much higher than that in the cough allergic asthma group. The allergic rhinitis group had a higher frequency of sensitization to a single inhaled allergen, while the bronchial asthma group had a higher frequency of sensitization to quadruple sensitization. For single inhaled allergens, the bronchial asthma group had a higher frequency of strong positive sensitization. Patients with allergic rhinitis who were sensitive to house dust had a 2.763-fold increased risk of developing bronchial asthma. Patients with cough allergic asthma who were sensitive to house dust mites, cat hair, or house dust had a 3-fold increased risk of developing bronchial asthma. Multiple sensitization increases the likelihood of cough allergic asthma transforming into bronchial asthma.</p></sec><sec><title>Conclusion</title><p>The most common allergens detected in this study were house dust mites, house dust, and mold. Children with bronchial asthma were associated with sensitization to most inhaled allergens, especially strong positive sensitization and multiple sensitization.</p></sec>

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MicroRNA-155 is a critical regulator of regulatory T cells in OM-85 Broncho-Vaxom treated experimental models of allergic rhinitis

<abstract><sec> <title>Background</title> <p>Bacterial lysates could alleviate the clinical symptoms of allergic rhinitis (AR) and decrease the recurrent rate of AR through regulation of regulatory T cell (Treg) cells. However, the molecular regulatory mechanisms of bacterial lysates to Treg are still unclear.</p> </sec><sec> <title>Objective</title> <p>We aimed to investigate the importance of microRNA-155 (miR-155) to Treg cells function in OM-85 Broncho-Vaxom (OM-85 BV) treated experimental mouse models of AR.</p> </sec><sec> <title>Methods</title> <p>AR mouse models were established and treated by intranasal administration of OM-85 BV to investigate the role of bacteria lysate for Treg cell function. The proliferation of Treg cells in peripheral blood was examined. The mRNA levels of IL-10, transforming growth factor-β (TGF-β) were examined by real-time PCR. miR-155 mimics and inhibitor were used to verify the role of miR-155 for Treg cells function.</p> </sec><sec> <title>Results</title> <p>OM-85 BV, miR-155 mimics or their combination reduced total cells, lymphocytes, neutrophils and eosinophils in nasal lavage fluid of AR mouse models and improved allergic symptoms. OM-85 BV promoted the proliferation of Treg and the expression of Foxp3, IL-10 and TGF-β both <italic>in vivo</italic> and <italic>in vitro</italic>. The miR-155 enhanced the proliferation and function of Treg.</p> </sec><sec> <title>Conclusions</title> <p>MiR-155 promotes Treg cells function in OM-85 BV bacteria lysate treated experimental models of AR and alleviate the upper airway allergic inflammation in AR mice.</p> </sec></abstract>

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Aeroallergen sensitization patterns in children with allergic rhinitis from Guangzhou and Liuzhou in southern China

<sec><title>Background</title><p>The sensitization patterns of allergic rhinitis (AR) to allergens exhibit global variations, influenced by diverse geographical, climatic, cultural, and genetic determinants. We aimed to contrast the allergen profiles among children belonging to distinct ethnic groups residing in two disparate provinces of China, with the objective of elucidating the impact of environmental and genetic factors on the types of allergens.</p></sec><sec><title>Methods</title><p>A comparative analysis was conducted on allergen sensitizations among children with allergic rhinitis (AR) in Guangzhou and Liuzhou from 2019 to 2023. The specific IgE response to a range of inhalant allergens was evaluated utilizing the ImmunoCAP 100 system. Statistical analysis was conducted using the SPSS 20 software package. For comparisons, the Chi-square test or Fisher's exact test was employed, depending on the nature of the data and the assumptions of each test.</p></sec><sec><title>Results</title><p>A total of 9684 AR children from Guangzhou and 1679 from Liuzhou were enrolled in the study. Notably, the sensitization rates toward D. <italic>farinae</italic>, <italic>D. pteronyssinus</italic>, cat dander, dog dander, common ragweed, and mugwort were significantly elevated in Guangzhou compared to Liuzhou. However, the sensitization rates to cockroaches exhibited no notable disparities between the two cities.</p></sec><sec><title>Conclusions</title><p>The allergen composition in AR children is similar between Guangzhou and Liuzhou, with <italic>D. farina</italic> and <italic>D. pteronyssinus</italic> as the main allergens. However, the sensitization rates of all allergens except for cockroaches in Guangzhou are higher than those in Liuzhou. Our results suggest that the causes of allergen sensitization are complex, and genetic and environmental factors cannot be ignored.</p></sec>

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