Background During the first 5 years of life, atopic individuals may develop cutaneous or respiratory symptoms with foodborne or airborne allergens. The route and dose of exposure are associated with sensitization. However, limited studies compare food and airborne allergies in these children. Objective To characterize and compare the developmental patterns of symptoms, specific IgE (sIgE)/specific IgG4 (sIgG4), and B cell subsets in response to food or airborne allergens under 5 years old. Methods Children aged from birth to 5 years old with food allergy and/or respiratory allergy symptoms were recruited from Jan 2019 to Dec 2021. Clinical parameters were systematically documented, and the sIgE responses to 29 common allergens were quantified via ImmunoCAP. A subset of participants (n = 45, with 9 cases in each age group) underwent assessments of sIgE/sIgG4 to egg, milk, and house dust mite (HDM) components. Peripheral B cell subsets were phenotypically characterized using multiparametric flow cytometry (n = 20). Results As the children ages, positivity rate to inhalant allergens (D. farina and D. pteronyssinus) rapidly increased to 57.04% and 58.23% respectively, while positivity for food allergens of eggs and milk dropped to 27.44% and 32.7%. Notably, allergen component-specific IgG4 levels against egg and milk allergens were significantly higher compared to those against HDM. However, all sIgG4 exhibited mild (0.3 < ρ < 0.52) or no correlation (ρ < 0.3) with corresponding components sIgE. Although most B cell subsets had no significant difference between the food and HDM sensitization, the tSNE analysis identified that the frequency of C6 (CD19+CD38+ IgG4+IgE++) effector B cells significantly increased in the 4–5 year HDM group, while memory B cell-like cells (C11, CD19+CD27+CD38+IgG4+) highly expressed in food allergies. Conclusions Our study demonstrates the frequency, route, and dosage of exposure may contribute to distinct variations in the repertoire of allergen-specific IgE/IgG antibodies and B cell subsets, highlighting the importance of exposure modalities in shaping early immune responses.

Objective The clinical presentation of atopic dermatitis (AD) varies significantly by age and geographic region. This study aimed to characterize the clinical features and identify risk factors associated with disease severity among AD patients in Central China. Methods This multicenter cross‐sectional study enrolled adult and pediatric AD patients presenting for initial visits at 12 tertiary medical centers in Central China between January 2024 and December 2024. We collected data on demographics, AD duration, comorbidities, triggers, prior treatments, and patient‐reported outcomes, including the Dermatology Life Quality Index (DLQI), and Atopic Dermatitis Control Tool (ADCT) scores. Researchers assessed AD severity using the Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI), with moderate‐to‐severe disease defined as SCORAD ≥ 25. Results A total of 2124 patients were included (45.0% female; mean age 36.2 years; 29.2% aged < 18 years). Mean AD duration was 4.54 years. Overall, 84.3% had moderate‐to‐severe AD, with the highest proportion observed in elderly group (91.7%). Comorbid allergic conditions (allergic rhinitis, food allergy, etc.) were present in 65.2% of the patients, with a higher prevalence among children (72.5%). Median scores were 43.00 for SCORAD, 6.00 for EASI, 10.00 for ADCT, and 9.00 for DLQI. Treatment history showed that 99.8% had received prior therapy, primarily topical corticosteroids (53.3%), topical calcineurin inhibitors (8.9%), or systemic corticosteroids and/or immunosuppressants (6.97%). Only 28.0% demonstrated good disease control (ADCT < 7) at the initial visit. SCORAD scores correlated positively with EASI, ADCT, and DLQI scores ( r = 0.716, 0.501, and 0.501, respectively, all p < 0.001). Multivariable analysis identified age, family history of AD, suburban residence, sunlight exposure, sleep disturbances, and skin friction as independent factors influencing AD severity. Conclusion Our study demonstrates a high burden of moderate‐to‐severe AD across Central China, accompanied by severe quality‐of‐life impairment and inadequate disease control. Age, suburban residence, and sleep disturbances emerged as independent risk factors, and notable seasonal trends were observed. These findings support the implementation of region‐specific, environment‐adaptive strategies for AD prevention and treatment.

BACKGROUND:Allergen immunotherapy (AIT) is the only etiological treatment for allergic rhinitis (AR) patients, yet the impact of allergen sensitization patterns on AIT efficacy remains unclear. This study aimed to assess the effectiveness of subcutaneous immunotherapy (SCIT) using a native house dust mite (HDM) allergen extract in Chinese AR patients with diverse HDM sensitization patterns. METHODS:This prospective multicenter study across three allergy centers in China enrolled patients aged 5-65 diagnosed with HDM-induced AR. Serum-specific IgE testing for nine HDM components (Der p1, Der p2, Der p23, Der f1, Der f2, Der p5, Der p7, Der p10, Der p21) categorized patients into two groups: Group A with sensitization limited to major allergen components and Group B with sensitization to minor components with or without major components. Both groups underwent 1 year of HDM SCIT (Allergopharma, Germany), whose efficacy was assessed using the visual analogue scale (VAS) and combined symptom medication scores (CSMS). Serum IgE and IgG4 levels against the nine HDM components were measured pre- and post-treatment, and SCIT-related adverse reactions were recorded. RESULTS:The study enrolled 168 patients, with 75 in Group A and 93 in Group B. Group B patients had higher asthma prevalence and elevated baseline HDM sIgE and total IgE levels. After 1 year, Group B showed significantly greater CSMS reduction (67.70% vs. 59.09%, p = 0.03) and VAS improvement (66.67% vs. 50.00%, p = 0.01) compared to Group A. Group A had increased new sensitization risk to minor allergens (Der p5, Der p7, Der p21). No significant difference in SCIT efficacy was observed between patients with and without new sensitization. Both groups exhibited increased sIgG4 levels against all nine HDM allergens, with a more pronounced elevation of sIgG4 levels to Der p21 observed in Group B compared to Group A (p = 0.02). SCIT-related adverse reactions were comparable (p > 0.05). CONCLUSIONS:The native HDM allergen extract demonstrates efficacy in Chinese AR patients with varying sensitization patterns. It offers enhanced benefits for patients sensitized to minor allergens with or without major allergens of HDM, positioning it as the preferred option for individuals with AR. TRIAL REGISTRATION:Chinese Clinical Trial Registry identifier: ChiCTR2300078642.

Background:Atopic dermatitis (AD) is a chronic inflammatory skin disease often accompanied by comorbidities such as allergic rhinitis (AR) and asthma. Dupilumab, a monoclonal antibody targeting IL-4Rα, has demonstrated significant efficacy and safety in the treatment of AD. However, its effectiveness in patients with comorbidities remains underexplored. We aimed to evaluate the impact of Dupilumab on the severity of dermatitis, comorbidity control, medication safety, and treatment adherence in Chinese AD patients in real-world settings. Methods:This is a single-center retrospective-prospective real-world cohort study that included 376 patients with AD who received Dupilumab treatment from February 2021 to February 2024. Among them, 270 patients had AD, and 106 had AD with comorbidities, including 106 cases of AR and 20 cases of asthma. Baseline clinical data and laboratory parameters were collected. The severity of AD, quality of life, and comorbidity control were assessed at week 0, 4, 8, 12, and 16. Efficacy indicators and related predictive factors were evaluated, and drug continuation rates at week 52 were assessed. Results:After 16 weeks of Dupilumab treatment, the median improvement in EASI score was 95.3% (from 8.5 to 0.40), with an EASI75 response rate of 78.9%. AD efficacy-related scores and comorbidity-related scores showed significant improvement compared to baseline (all P<0.05). There was no statistical difference in efficacy between the AD group and AD with comorbidities group. Drug survival analysis showed similar drug continuation rates at 52 weeks for both groups (P>0.05). Adverse events were mainly eye-related events (8.51%, 32/376), followed by localized symptom worsening (2.13%), hair loss (1.60%), and facial erythema (1.33%). Patients with higher baseline EASI scores were more likely to achieve 90-100% improvement (P = 0.024). Conclusion:Dupilumab effectively improves AD symptoms and comorbidities, with consistent efficacy across comorbid status and good safety profile. Higher baseline disease severity associates with better treatment response.

Objective: Allergen immunotherapy (AIT) and dupilumab have been confirmed to improve symptoms of atopic dermatitis (AD); however, the precise immune mechanisms underlying their efficacy and whether they can elicit synergistic immune effects remain not fully elucidated. We aimed to investigate the clinical efficacy and immunological changes in AD patients undergoing AIT, dupilumab, and a combination of AIT and dupilumab treatment. Methods: Clinical data, serum samples, and peripheral blood mononuclear cells (PBMC) were collected from house dust mite (HDM)-sensitized AD patients receiving AIT and/or dupilumab at baseline and 6 months. Changes in clinical efficacy, HDM-specific IgE and IgG4, serum cytokines, and lymphocyte subgroups were compared among the treatment groups. Results: A total of 77 AD patients were included, with 39 in the AIT group, 19 in the dupilumab group, and 19 in the AIT combined dupilumab group. The SCORAD scores significantly improved in all groups after 6 months. Levels of HDM-specific IgE and total IgE remained stable in the AIT group but decreased in the dupilumab and combination groups. Levels of IgG4 against major mite components Der p1 and Der p23 increased in the AIT group and combined treatment group. Serum cytokine levels showed no significant changes, except for a decrease in CCL17 in the dupilumab group. Th1/Th2 and Th17/Th2 ratios increased after dupilumab treatment. There were notable differences in T cell subpopulations when PBMCs were stimulated with HDM extracts after 6-month treatment, tSNE analysis showed the proportion of IL-4+IL-13+CRTH2+T cells increased in the dupilumab group but had no changes in the AIT and combination group. Conclusions: AIT, dupilumab, and their combination improved clinical symptoms and quality of life in AD patients. AIT promoted allergen-specific IgG4 production, while dupilumab modulated T cell responses and reduced allergen-specific IgE synthesis. The combination of AIT and dupilumab exhibited the immunological parameter changes characteristic of both treatments but did not result in a significantly greater improvement in AD symptoms.

(1) Background: The prevalence of allergic rhinitis (AR) and asthma has increased rapidly in China. However, perceptions of respiratory allergies and barriers to their management have not attracted enough attention. (2) Objective: To investigate the prevalence of, parents’ perceptions of and their unmet needs for information concerning respiratory allergies in a 3- to 16-year-old children population. (3) Methods: A cross-sectional survey was conducted from June to July 2021 in three schools in Wuhan, China. A total of 1963 participants were recruited through cluster sampling for their parents to complete an online questionnaire regarding respiratory allergic symptoms. The diagnosis of respiratory allergies was based on self-reported symptoms and face-to-face physician evaluation. All the participants with respiratory allergies were asked to complete the Brief Illness Perception Questionnaire (B-IPQ), the Asthma Knowledge Questionnaire (AKQ) and a questionnaire regarding their unmet needs for disease management. (4) Results: The prevalence of respiratory allergies was 29.3% (576/1963) in the 3- to 16-year-old population, among whom AR accounted for 25.7%; asthma, 1.8% and AR-complicated asthma (AR&Asthma), 1.9%. The total B-IPQ score was 40.2 ± 10.9 in the participants with respiratory allergies, and there were no differences among the AR, asthma and AR&Asthma groups (all p > 0.05). The B-IPQ score correlated significantly with symptom onset time and a history of atopic dermatitis (p < 0.01). Nearly one fifth, 18.9%, of the participants with respiratory allergies never went to hospital for treatment, but those with higher B-IPQ scores were more likely to seek professional treatment (p < 0.001). The accuracy rates of AKQ were 72.5% in the participants with asthma and 76.7% in those without asthma (p = 0.147). Among the 576 participants with respiratory allergies, 568 (98.6%) had tried to obtain disease-management information from online platforms, and 55.5% (315/568) were dissatisfied with current platforms; the reasons included incomprehensive contents of illness (45.7%), lack of voice from leading experts (40.3%), too many advertisements (37.5%) and similar contents on different platforms (36.8%). (5) Conclusions: The prevalence of respiratory allergies is high in the 3- to 16-years old population in Wuhan, China. Yet the parents’ perceptions of respiratory allergies and knowledge of asthma are insufficient. It is crucial to increase parents’ awareness of the illness and facilitate their access to truly informative and professional platforms.

Nowadays, the management of food allergies has increasingly moved from conventional oral immunotherapy (OIT) to low-dose OIT or low-dose OIT utilizing hypoallergenic foods. This shift is largely because the latter appears to induce oral tolerance with fewer adverse effects than the former. However, the mechanisms underpinning such differences remain unclear. To better understand these mechanisms, we conducted a comparative study scrutinizing the mechanisms of OIT, especially those of low-dose desensitization. We also summarized articles on low-dose OIT and low-dose OIT using hypoallergenic foods. We examined the efficacy, safety, and immunological parameters of low-dose OIT and those of low-dose OIT with hypoallergenic foods with the aim of shedding some light on low-dose OIT and its therapeutic application in inducing oral tolerance for individuals with food allergies.

Anaphylaxis is a severe systemic hypersensitivity reaction with acute onset that can potentially be fatal. Currently, the worldwide incidence stands at approximately 46 cases per 100,000 people annually, with rates fluctuating between 0.49 and 328.7 per 100,000 person years1, with considerable variation across age groups and regions. Despite increasing global awareness, research into the prevalence of anaphylaxis within the Chinese population remains sparse. In this retrospective epidemiological study in Wuhan, China, we identified anaphylaxis cases among outpatients using the World Allergy Organization's (WAO) 2020 updated guidelines.2 Acute onset was defined within 6 h post-exposure.3 Potential cases were initially screened via relevant diagnoses (Appendix 1) from the Data Platform Application Portal (DPAP) of Tongji Hospital, Wuhan, China from January 1, 2019, to December 31, 2023. We transformed guidelines into practical descriptions for medical records (Appendix 2). Screening was performed using PyCharm, followed by manual review and data extraction from medical records (Figure 1). The study was approved by the Tongji Hospital IEC (NO. TJ-IRB202401061) with an informed consent waiver. We identified 1026 anaphylaxis patients from a cohort of 6,280,013 outpatients with a female predominance (54.8%) and a median age of 29 years. The crude annual incidence rate was 16.34 per 100,000, which increased to 154.72 after adjusting for age and gender. We observed an increasing trend in incidence over the study period, peaking among adolescents (Figure 1). Identifiable triggers were present in 74.9% (798/1066) of cases, with drugs leading at 40.7% (434/1066). Antibiotics and allergen extracts dominated, accounting for 40.6% (176/434) and 15.9% (69/434). Food followed, contributing to 27.0% (288/1066), showed age-specific features: dairy products were predominant in infants and toddlers (33.3%, 19/57), while seafoods were more common in other age groups (Table 1). Alarmingly, only 10.8% (115/1066) of patients received epinephrine, despite its critical role in anaphylaxis management, with a declining trend in its use over 5 years. Glucocorticoids, antihistamines, calcium gluconate, and bronchodilators were frequently administered. In addition, other medications such as acid-suppressing drugs, water-soluble vitamins, and glucose saline solutions were also widely used in the treatment of anaphylaxis. Notably, 84 patients (8.2%) experienced recurrent episodes, with no fatalities reported. The anaphylaxis incidence rate from our study exceeds some English-speaking regions.4 This may reflect the population and variations in anaphylaxis definitions and diagnostic methods. An annual increment in anaphylaxis incidence was noted, plateauing from 2020 to 2022, suggesting impacts from COVID-19 and resource limitations. Drugs and food were predominant triggers, with age-specific food allergen patterns observed. These data reflect regional, lifestyle, and genetic influences on allergen distribution.5 It is noteworthy that allergen extracts were the second highest drug-related trigger for anaphylaxis, with 55.1% (38/69) caused by crude allergen extracts (Appendix 3). This could be due to the fact that more than 3000 outpatients receive subcutaneous immunotherapy treatments at our center annually, and anaphylaxis induced by subcutaneous immunotherapy is not uncommon. Alarmingly, epinephrine use for anaphylaxis treatment has declined to a mere 10.8%, lower than other Chinese studies (14.2%–25%).6 This reflects a notable lack of awareness and understanding of anaphylaxis among our medical practitioners. In clinical settings, there is often hesitation to administer epinephrine promptly to patients experiencing anaphylaxis without shock. This reluctance stems from concerns about potential adverse reactions, including the induction of malignant arrhythmias. As a result, the use of epinephrine is largely confined to critical scenarios. This study's limitations include potential recall bias and variability in medical record documentation. Besides, serum tryptase detection kits have not yet received marketing approval in China, which precludes the possibility of using serum tryptase to further verify the diagnosis of anaphylaxis in patients initially identified by our physicians. Also, unmeasured confounding factors cannot be eliminated, such as the population consists of patients seeking medical treatment. It is noteworthy that while the DPAP system is restricted to internal hospital use and is not transferable, the extensive data set of 75 million medical records from over 16 million patients mitigates some biases. RZ and PD conceived and designed the project. LL and HC set up the data screening procedure and generated the figures. LL, NH, WL, YY, and DM manually screened and collected the patients' information. LL wrote the first draft of the manuscript, RZ and PD revised the raw manuscript. All authors critically revised the manuscript and approved the submitted manuscript. We would like to thank the Tongji Hospital affiliated with Huazhong University of Science and Technology for providing the data platform used in this study. This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Thus, there are no funding information to report. There are no financial or other issues that might lead to conflict of interest. None, without accompanying symptoms, denying symptoms, not seen, not reported by the patient, not experienced by the patient, if present, if there is any, occasionally present, intermittent. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Background:The incidence of a disease can help health professionals to identify risk factors and health-care policymakers to develop corresponding policies. The realization of both purposes depends on comprehensive studies, especially studies done on a large scale. However, comprehensive studies on the incidence of anaphylaxis among inpatients in China are still notably scarce. Hence we aim to explore the incidence and clinical characteristics of anaphylaxis among inpatients over a span of 21 years in Wuhan, China. Methods:We retrieved data on anaphylaxis cases from the Data Platform Application Portal (DPAP) across 3 medical centers of Tongji Hospital, Wuhan, China from January 1, 2003, to December 31, 2023. Results:The data encompassed a total of 362 anaphylaxis patients from 2,139,272 inpatients. Among them 204 (56.4%) were male, and the median age was 45 years old. Over the past 2 decades, the incidence rate of anaphylaxis at Tongji Hospital was 16.92 per 100,000 individuals. After adjusting for gender and age, the annual standardized incidence rate was 234.53 per 100,000 individuals. The incidence rate of anaphylaxis among the inpatients revealed a relatively stable but slowly rising trend over the 21-year observation period. As for the triggers of anaphylaxis, drugs were responsible for 73.6% of triggers, with antibiotics representing the highest proportion of these cases (38.4%). Drug triggers also showed age-specific features: chemotherapy (17.9%) had the highest proportions among children aged 0-3 years; blood products were more prevalent in school-age children. 13.5% of the cases had an unknown cause. In anaphylaxis cases, despite that only 36.0% received epinephrine treatment, the application of epinephrine still showed an ascending trend. Moreover, the mortality rate for anaphylaxis was relatively low (1.6%), displaying a consistent downward trend. Conclusion:Our study provides insights into the incidence of anaphylaxis among inpatients in Wuhan over a 21-year period. Drugs are the most common triggers for anaphylaxis, and the use of epinephrine in anaphylaxis management is far from optimal.

Introduction: Airborne fungi induce allergic symptoms in 3–10% of the population worldwide. To better prevent and manage fungi-related allergic diseases, it is essential to identify the genus and the distribution profile of airborne fungi. Methods: With this purpose in mind, we carried out a 12-month volumetric sampling study to monitor the airborne fungi and retrospectively analyzed the sensitization profile of four dominant fungi (Cladosporium, Alternaria, Aspergillus, and Penicillium) among respiratory allergies during the same study period in Wuhan, China. Results: A total of 29 different fungal genuses were identified, and the peak fungal concentration period was found to be in September and October, followed by May and June. The most prevalent fungi in this area were Cladosporium (36.36%), Ustilago (20.12%), and Alternaria (13.87%). In addition, the skin prick test data from 1,365 respiratory allergies patients showed that 202 (14.80%) of them were sensitized to fungi. The sensitization rates to Cladosporium, Alternaria, Aspergillus, and Penicillium were 11.72%, 4.69%, 1.98%, and 4.76%, respectively. The seasonal fluctuation of Alternaria and Aspergillus correlated with their sensitization rates. Among the fungal sensitized patients, 76 (37.62%) were sensitized to two or more kinds of fungi. The serum-specific IgE tests suggested low to high correlations existed between these fungi; however, these correlations were not found between fungi and other allergens. Conclusion: Our study provides the distribution profile and reveals the clinical significance of the airborne fungi in Wuhan, which will facilitate the precise management of fungal allergy.

Previous studies suggest that allergic diseases may be a protective factor in SARS-CoV-2 infection. However, data regarding the impact of dupilumab, a widely used immunomodulatory medication, on COVID-19 in an allergic population are very limited. To investigate the incidence and severity of COVID-19 among moderate-to-severe atopic dermatitis (AD) patients treated with dupilumab, a retrospective cross-sectional survey was conducted among patients with moderate-to-severe AD who presented at the Department of Allergy of Tongji Hospital from 15 January 2023 to 31 January 2023. Healthy individuals matched for gender and age were also enrolled as a control. All subjects were asked about their demographic characteristics, past medical history, COVID-19 vaccination history, and medications, as well as the presence and duration of individual COVID-19-related symptoms. A total of 159 moderate-to-severe AD patients and 198 healthy individuals were enrolled in the study. Among the AD patients, 97 patients were treated with dupilumab, and 62 patients did not receive any biologicals or systemic treatments (topical treatment group). The proportions of people who were not infected with COVID in the dupilumab treatment group, topical treatment group and healthy control group were 10.31%, 9.68% and 19.19%, respectively (p = 0.057). There was no significant difference in COVID-19-related symptom scores among all groups (p = 0.059). The hospitalization rates were 3.58% in the topical treatment group and 1.25% in the healthy control group, and no patient was hospitalized in the dupilumab treatment group (p = 0.163). Compared with healthy control group and topical treatment group, the dupilumab treatment group had the shortest COVID-19-associated disease duration (dupilumab treatment group, 4.15 ± 2.85 d vs. topical treatment group, 5.43 ± 3.15 d vs. healthy control group, 6.09 ± 4.29 d; p = 0.001). Among the AD patients treated with dupilumab for different times, there was no appreciable difference (<0.5 year group, 5 ± 3.62 d vs. 0.5–1 year group, 4.84 ± 2.58 d vs. >1 year group, 2.8 ± 1.32 d; p = 0.183). Dupilumab treatment shortened the duration of COVID-19 in patients with moderate-to-severe AD. AD patients can continue their dupilumab treatment during the COVID-19 pandemic.

allergens might be co-sensitized to other prevalent allergens such as HDM, which restrained their contribution in increasing positive rate when we used the step-by-step conditional method to determine the minimal allergen pane. 5 are aware of the limitations of our study such as not including specific IgE tests and some clinically relevant allergens (e.g., Morus, Broussonetia).However, we still provide a comprehensive knowledge of prevalent aeroallergens that is required for the diagnosis of AR in China.Although the prevalent allergens were different in those centers, HDMs are still the major allergens in Chinese AR patients, and the sensitization rates to cat, dog and Humulus pollen showed increasing trends in the last decade. AUTH O R CO NTR I B UTI O N SZR and CH conceived and designed the project.WY, ZX, and DW acquired the data.WY and CH did the statistical analysis.

Bone marrow adipose tissue (MAT) has the potential to exert both local and systemic effects on metabolic homeostasis. As a first-line drug used to treat type 2 diabetes mellitus, metformin has conflicting effects on MAT and bone marrow mesenchymal stem cell (BM-MSC) differentiation. Through a series of experiments in vivo and in vitro, we found that except improving the glucose and lipid metabolism disorder in ob/ob mice, 200 mg/kg metformin increased MAT in mice tibia, and prompted osteogenic genes (RunX2, OPN, OCN) and lipogenic genes (Ppar-γ, Cebpα, Scd1) expression in mice bone marrow. However, metformin promoted osteogenesis and inhibited lipogenesis of MSC in vitro, which is inconsistent with the results in vivo. Given MAT being considered the "filler" of the space after the apoptosis of bone marrow stroma, the effect of metformin on MSC apoptosis was examined. We discovered that metformin induces MSC apoptosis in vivo and in vitro. Therefore, we speculated that the increased MAT in mice tibia may be attributed to the filling of adipose tissue after apoptosis of bone marrow stromal cells induced by metformin. The increased MAT may be involved in the regulation of metformin on glucose, lipid, and bone metabolism in diabetic mice, providing a new way to understand the metabolic regulation of metformin. While increased MAT-associated insulin resistance and metabolic disorders may account for the poorer clinical benefits in patients with intensive glucose control.

提到过敏,大家想到的大多是皮疹、瘙痒.确实,这是过敏最常见的表现,但过敏远不止这些不适.过敏反应还可累及到呼吸道、消化道等系统,有时还可能发生过敏性休克等严重致死性反应. 过敏反应也称为变态反应,是指机体在受到同一种过敏原再次刺激后所引起的以功能紊乱或组织细胞损伤为表现的病理性免疫反应.

目的 探讨胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)对屋尘螨(house dust mite,HDM)诱导小鼠过敏性气道炎症的作用,并探讨其作用机制.方法 将24只SPF级C57/BL6小鼠随机分为对照(Con)组、GLP-1组、屋尘螨(HDM)组、屋尘螨+GLP-1(HDM+GLP-1)组.用HDM建立小鼠过敏性哮喘模型,选用临床常用的GLP-1类似物利拉鲁肽干预小鼠.HDM组,给予鼻腔滴注HDM诱导小鼠气道过敏性炎症,并给予等体积生理盐水皮下注射;HDM+GLP-1组,给予HDM鼻腔滴注,同时给予利拉鲁肽皮下注射;GLP-1组,给予利拉鲁肽皮下注射,并给予等体积生理盐水鼻腔滴注;Con组给予等体积生理盐水鼻腔滴注及皮下注射.通过HE染色观察肺组织病理学变化,流式细胞仪检测支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中不同Th细胞的比例,ELISA检测IL-4、IL-5、IL-13炎性因子的浓度.结果 HDM组小鼠肺组织病理损伤明显,GLP-1抑制屋尘螨诱导的小鼠气道过敏性炎症,降低Th2细胞比例(Th2,CD4+IL-4+:HDM 20.2±2.06％vs.HDM+GLP-19.57±3.66％,P<0.05),促进Th1/Th2细胞平衡.结论 GLP-1负向调节Th2细胞形成,促进T细胞向Th 1细胞方向分化,从而抑制屋尘螨诱导的小鼠气道过敏性炎症.

Background Aspergillus fumigatus (A.f) is a common airborne allergen that contributes to allergic asthma. In some patients, A.f can colonize in the airway and lead to allergic bronchopulmonary aspergillosis (ABPA). However, our understanding of the pathogenesis of A.f-sensitized asthma and ABPA remains inadequate. Objective We aimed to investigate the clinical and immunological characteristics of A.f-sensitized asthma and ABPA. Methods A total of 64 ABPA and 57 A.f-sensitized asthma patients were enrolled in the study, and 33 non-A.f-sensitized asthma patients served as the control group. The clinical and immunological parameters included lung function, fractional exhaled nitric oxide (FeNO), induced sputum and blood cell analysis, specific IgE/IgG/IgA of A.f and its components, cytokines (IL-33, IL-25, and TSLP) and CD4+T cell subsets. Results The eosinophils in blood, induced sputum, and FeNO were significantly higher in ABPA patients compared to that in A.f-sensitized patients. The combination of FeNO and eosinophils (EO) parameters presented good diagnostic efficiency in differentiating A.f (+) asthma from ABPA, with a sensitivity of 80% and a specificity of 100%. Specific IgE, IgG, and IgA against A.f also increased in ABPA patients. However, serum IL-25, IL-33, and TSLP showed no significant differences between the two groups. Cell analysis showed an increase in IFN-γ+Th1 cells in the ABPA patients. FlowSOM analysis further confirmed that the frequency of CD3+CD4+PD-1+CD127+IFN-γ+T cells was higher in ABPA patients. Conclusion Our findings suggest the distinct humoral and cell immunological responses in A.f-sensitized asthma and ABPA patients. ABPA patients have more severe eosinophilic inflammation and enhanced Th1 responses compared with A.f-sensitized asthma patients.

OBJECTIVE:Hereditary angioedema (HAE) is a rare, life-threatening autosomal dominant disorder. We aimed to investigate the prevalence of HAE in a Chinese population with a decreased Complement 4 (C4) level.METHODS:All the patients present in Tongji Hospital with C4 below lower normal range were included from January 2019 to June 2020. The individual data were extracted from the database and categorized by diagnosis. Patients suspected of HAE were further evaluated by C1 inhibitor level and function test to confirm the HAE diagnosis.RESULTS:A total of 8226 patients were enrolled in our study, among whom 18 had symptoms similar to HAE and received C1 inhibitor level and function tests. Two (1 male and 1 female) of the 18 patients were identified as HAE patients. This means the prevalence of HAE was 2.43/10 000 among the C4-decreased population and 10.1/10 000 in the C4-decreased population with etiology undetermined. The 2 HAE patients had experienced skin and oropharynx edema attack and received tracheotomy. The female patient had a family history. Laboratory tests showed significant decrease of C4 and C1 inhibitor levels in the 2 patients, both of whom were diagnosed as type 1 HAE.CONCLUSION:The prevalence of HAE is low in C4-decreased patients. In a large cohort, C4 level can serve as a practical indicator to screen the HAE patients, but further testing of C1 inhibitor activity and levels is needed to confirm the diagnosis of HAE.

BackgroundAllergen immunotherapy (AIT) can induce immune tolerance to allergens by activating multiple mechanisms, including promoting IgG4 synthesis and blunting IgE production. However, the longitudinal data of sIgE and sIgG4 to allergen components during AIT are limited.ObjectiveWe sought to investigate the persistence and evolution of sIgE and sIgG4 against house dust mite (HDM) components during AIT and explore their correlation with clinical responses.MethodsSixty allergic rhinitis (AR) with/without asthma patients receiving AIT for HDM were enrolled in AIT group. Thirty AR patients without receiving AIT served as control group. Blood samples were collected for sIgE, sIgG4 to HDM components (Derp 1, Derf 1, Derp 2, Derf 2, Derp 7, Derp 10, Derp 21 and Derp 23) assay at baseline, Month 6 and Month 18 of AIT. Combined symptom and medication scores (CSMS) were obtained accordingly.ResultsIn the AIT group, sIgG4 to the HDM components of Derp 1, Derf 1, Derp 2 and Derf 2, Derp 21 significantly increased at Month 18 compared to the baseline (36.2 UA/mL vs 158.8 UA/mL, 46.4 UA/mL vs 94.6 UA/mL, 80.5 UA/mL vs 152.3 UA/mL, 78.3 UA/mL vs 205.1 UA/mL, 42.3 UA/mL vs 59.3 UA/mL, all p<0.05), sIgE to HDM components didn’t see differences at baseline and at Month 18 (all p>0.05).The numbers of positive HDM component sIgE and sIgG4 increased from 4.5 to 5 and 0 to 1.5 respectively (both p<0.05). However, the changes of sIgE, sIgG4, sIgE/sIgG4 ratio and the numbers of positive HDM components had no correlations with the improvement of CSMS after AIT (all ρ<0.3). For the control group, the sIgE and sIgG4 did not change significantly during the observational period (all p>0.05).ConclusionAIT can induce the production of sIgG4 to HDM components. However, the increased sIgG4 levels of HDM component do not correlate with the corresponding sIgE levels at baseline or with AIT response. sIgG4 to HDM components do not qualify as a biomarker to evaluate the efficacy of AIT.

Introduction: Asymptomatic sensitization is defined as the presence of positive skin prick test (SPT) and/or positive serum allergen-specific IgE in the absence of clinical allergic symptoms. Currently, there is no convincing explanation why some people with positive allergen tests do not show symptoms. We aimed to investigate the house dust mite (HDM)-specific IgE and IgG4 repertoire in asymptomatic HDM-sensitized subjects and HDM-induced allergic rhinitis (AR) patients. Methods: A total of 48 subjects sensitized to HDM were included in this study: 27 had AR with/without asthma (symptomatic group), and 21 had no allergic symptoms (asymptomatic group). Six healthy individuals served as control group. Peripheral blood samples were collected for serum IgE and IgG4 assay and basophil activation tests (BATs). IgE and IgG4 assay included antibodies to Dermatophagoides (Der) p1, 2, 7, 10, 21, 23, and Der f1, 2. Results: AR patients had a larger wheal diameter of SPT (7.0 vs. 3.0 mm, p < 0.0001) and a higher specific IgE to Der p (15.50 vs. 0.70 KU/L, p < 0.0001) than asymptomatic subjects. They also showed more frequent sensitization to Der p1 and Der p2 (both p < 0.05). However, the total IgE and specific IgG4 did not differ significantly between the 2 groups. The basophil activation response after being stimulated with HDM was observed to be higher in AR patients (all p < 0.05). Conclusions: There are differences in SPT, serum-specific IgE to Der p, component allergen Der p1 and Der p2 level and BAT between AR patients and asymptomatic subjects sensitized to HDM. IgG4 alone cannot differentiate asymptomatic individuals from AR patients.

目的:体外诱导扩增获取大量高纯度小鼠骨髓来源树突状细胞(dendritic cells,DC),并研究DC不同生长状态、不同培养时间的生物学特性差异.方法:重组小鼠粒细胞巨噬细胞集落刺激因子(recombinant-murine granulocyte-macrophage colony-stimulating factor,rmGM-CSF)体外诱导小鼠骨髓细胞分化为DC,在培养接种后0h及1 d、4 d、7 d、9 d、11 d用倒置光学显微镜动态观察DC的数量、存活率及形态学变化.分别收集9d不加入重组小鼠白细胞介素-4(recombinant mouse interleukin-4,rmIL-4)及加入rmIL-4刺激的悬浮细胞和贴壁细胞,流式细胞术(flow cytometry,FACS)检测悬浮细胞和贴壁细胞表面分子CD11c、CD80、CD86、MHC-Ⅱ的表达水平.收集培养9 d、11 d的DC,利用FACS分析BMDC细胞CD11c表达水平.采用SPSS 17.0软件进行统计学分析,两独立样本间的比较采用t.检验.结果:培养0h及1 d、4 d、7 d、9 d、11 d的BMDC成活率均为90％～95％.培养4 d,大量集落细胞团形成并逐渐增多.培养9 d,细胞明显变大,表面可见明显不规则树突或伪足.培养9 d,流式细胞术显示悬浮细胞表面标志CD11C+CD80+、CD11C+CD86、CD11C+MHC-Ⅱ的表达比例分别为(88.10±2.41)％、(84.60±3.26)％、(92.90±3.93)％,高于贴壁细胞的(79.17±2.32)％、(75.40±4.41)％、(82.77±4.80)％,差异有统计学意义(P＜0.05).加人rrnJL-4刺激与不加入rmIL-4 BMDC中CD11c+表达差异无统计学意义(P＞0.05).培养11 d,悬浮细胞及贴壁细胞的CD11c+表达明显高于培养9d的表达(P＜0.05).结论:体外简易诱导培养可以获得高纯度小鼠骨髓来源的各具特性DC;rmGM-CSF单独或者联合rmIL-4诱导刺激对DC特异表面标志物CD11c+无明显影响;悬浮细胞的成熟度高于贴壁细胞;延长培养时间可提高CD11c+DC的产量及纯度.