Purpose:There are limited studies on the intestinal microbiome in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA), and changes in the gut microbiome in WDEIA patients after wheat-free diet have not been studied. Methods:This is a cross-sectional analysis. Fecal samples and clinical data were collected from 26 non-wheat-free patients with WDEIA, 11 wheat-free patients with WDEIA, and 24 healthy controls (HCs). The gut microbiota was evaluated through metagenomic sequencing. Results:The sequencing revealed differences in the gut microbiome between patients with WDEIA on a non-wheat-free diet and HCs; more specifically, the non-wheat-free group exhibited a downregulation of two families (Rikenellaceae and Odoribacteraceae), three genera (Alistipes, Odoribacter, and Catenibacterium), and four species (Bacteroides_stercoris, Alistipes_putredinis, Bacteroides_intestinalis, and Bacteroides_cellulosilyticus). A wheat-free diet is associated with intestinal flora more similar to the structure of healthy individuals. The species Bacteroides_stercoris was negatively correlated with T-IgE, and the genus Catenibacterium was negatively correlated with T-IgE, as well as wheat, gluten, or gliadin-specific IgE. The genus Catenibacterium was positively correlated with the healthy control-enriched "Apoptosis (ko04210)" pathway and negatively correlated with the non-wheat-free WDEIA group-enriched "Thyroid hormone signaling pathway (ko04919)" pathway. Conclusion:Patients with WDEIA exhibit a specific gut microbiota signature and function, which demonstrated the potential association between the gut microbiome and WDEIA development. WDEIA patients on a wheat-free diet exhibit a gut microbiome composition more similar to healthy individuals.

Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment for allergic diseases, but current crude-extract-based approaches suffer from poor standardization and variable safety and efficacy. This study developed lipid nanoparticle (LNP)-encapsulated mRNA vaccines encoding Der p 1 and Der p 2, the major house dust mite (HDM) allergens, and evaluated them in a murine model of HDM-induced airway inflammation. LNP-mRNA vaccines triggered potent humoral immunity and exhibited good tolerability. Subcutaneous immunotherapy significantly reduced early allergic responses, airway hyperresponsiveness, eosinophil infiltration, and mucus hypersecretion. Compared with HDM extract, LNP-mRNA more effectively suppressed T helper cell 2 (Th2)-driven inflammation, decreased total and HDM-specific IgE, and induced allergen-specific blocking antibodies. Specifically, Der p 1/2-specific IgG1 and IgG2a titers increased by more than 10-fold, markedly inhibiting basophil activation. Mechanistically, LNP-mRNA enhanced regulatory T cell (Treg) and type 1 Treg (Tr1) populations, restored Th1/Th2 balance with an approximately 2-fold increase in Th1 cells, reduced innate lymphoid cell 2 (ILC2) frequencies, and promoted germinal center B and T follicular helper responses. Innate immune activation was also observed, with elevated dendritic cells type 1 (cDC1), dendritic cells type 2 (cDC2), and plasmacytoid dendritic cells (pDC) frequencies. These results demonstrate that HDM LNP-mRNA vaccines are safe, are immunologically potent, and represent a standardized next-generation approach for AIT.

BackgroundAsthma remains a global health burden, affecting over 300 million individuals worldwide, with its pathogenesis involving complex interactions between genetic predisposition and environmental allergens. Pollen is a well-established trigger of allergic asthma. However, the precise mechanisms underlying its allergenic activity remain incompletely understood. Recent advances have highlighted the emerging role of plant-derived extracellular vesicles in immune modulation. Notably, pollen-derived extracellular vesicles (PDEVs) have been identified as carriers of allergenic proteins. Therefore, this study investigates whether pollen contains extracellular vesicles(EVs) and whether these vesicles can induce allergic airway inflammation.MethodsWe isolated extracellular vesicles from Artemisia annua pollen using differential centrifugation and sucrose density gradient ultracentrifugation. The biological activity of PDEVs was evaluated in vitro using human airway epithelial cells (BEAS-2B) and in vivo using a murine asthma model.ResultsPDEVs are nanoscale lipid bilayer structures containing diverse allergenic proteins and exhibiting structural stability. PDEVs induced significantly stronger pro-inflammatory responses compared to pollen supernatant (Sup) in vitro. PDEVs enhanced inflammatory cytokine production IL-4, IL-5, IL-13, IL-33 expression, and promoted eosinophilic, neutrophilic infiltration in murine.ConclusionOur findings suggest extracellular vesicles present in pollen grains, which may represent a critical mechanism underlying pollen-induced airway inflammation. Targeting PDEVs may offer new therapeutic strategies for allergic airway diseases prevention and treatment.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the cellular images shown in Fig. 7A on p. 995 were strikingly similar to data in a paper that had previously been published in the journal Molecular Cancer that was written by different authors at different research institutes. Furthermore, an independent analysis of the data in this paper performed by the Editorial Office revealed that flow cytometric data in Fig. 2A, the cell migration and invasion assay data in Fig. 3A and D and the control western blot data in Fig. 5A were also strikingly similar to data that had either previously been published in articles written by different authors at different research institutes, or which were submitted for publication at around the same time. Given that the abovementioned data had already been published before the receipt of this paper at International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 42: 988‑997, 2018; DOI: 10.3892/ijmm.2018.3685].

Food-induced anaphylaxis (FIA) is a life-threatening allergic reaction, while wheat-dependent exercise-induced anaphylaxis (WDEIA) is triggered by wheat ingestion plus cofactors. To elucidate their differences, we profiled serum extracellular vesicle (EV) proteomes from 240 participants, including WDEIA, FIA, oral allergy syndrome (OAS), and healthy controls. All blood samples were obtained at least one month after the most recent acute allergic reaction, using TMT-based LC-MS/MS with ELISA validation. A total of 583 EV proteins were confidently identified, revealing distinct immune features. Compared with controls, EV-derived C1-inhibitor (C1-INH) significantly decreased in both WDEIA and FIA, showing diagnostic potential for systemic anaphylaxis. Seventy-six proteins differed between WDEIA and FIA, with reduced apolipoprotein E (APOE) in FIA and elevated eosinophil cationic protein (ECP) in WDEIA, both exhibiting good discriminatory power. These findings indicate that serum EV proteomics can reveal unique immune signatures and identify C1-INH, APOE, and ECP as potential biomarkers distinguishing food-related anaphylaxis subtypes.

Objective:Artemisia pollen is a major airborne allergen in northern China; however, the relative contributions of environmental pollen exposure and host susceptibility to allergic disease remain unclear in high-exposure regions. Methods:A population-based cross-sectional study was conducted in Yulin City, China, involving 12,345 participants recruited through multistage stratified cluster sampling. Serum Artemisia-specific IgE was measured in 3,130 participants. Disease status was classified into healthy, sensitized, allergic rhinitis, and acute asthma exacerbation groups. Regional pollen exposure was categorized into low, medium, and high levels based on monitoring data. Inverse probability weighting was applied to reduce selection bias. Multivariable logistic regression models were used to assess associations. Results:The IPW-adjusted prevalence of Artemisia sensitization, allergic rhinitis, and acute asthma exacerbations was 13.0%, 10.7%, and 1.9%, respectively. Regional pollen concentration was not significantly associated with sensitization or disease outcomes in adjusted models (all P > 0.05). In contrast, host-related factors, including family history of allergy and Artemisia-specific IgE levels, showed consistent associations across disease stages. Family history of allergy was strongly associated with sensitization (OR = 4.57, 95% CI: 3.01-6.95). Increasing Artemisia-specific IgE levels were associated with higher odds of progression from sensitization to clinical disease and from rhinitis to acute asthma exacerbation. Conclusion:In this high-exposure population, host susceptibility factors demonstrated stronger and more consistent statistical associations with Artemisia-related allergic disease than regional pollen concentration. These findings suggest that host heterogeneity may contribute importantly to disease variability in high-exposure environments; however, causal inference is limited by the cross-sectional design and exposure measurement constraints.

Allergic cross-reactivity among different fungal species appears to be widely existing. Fungus-related foods, such as edible mushrooms, mycoprotein, and fermented foods by fungi, can often induce to fungus food allergy syndrome (FFAS) by allergic cross-reactivity with airborne fungi. This article presents a case study of an individual with mold allergy who experienced anaphylaxis after consuming seafood mushrooms. This study indicated that Alt a 1 mediating cross-allergy between Alternaria alternata and Hypsizygus marmoreus, which has not been documented in the literature concerning the FFAS. Mushrooms tend to induce anaphylaxis in patients with mold-allergy and warrants clinicians' attention.

BackgroundPeach allergy is common food allergen. Allergen components-specific antibodies of different isotypes in peach-allergy patients are poorly studied. Factors other than Pru p 3-sIgE levels may be related to severe symptoms.ObjectiveTo evaluated peach component-specific-IgE, IgG1, and IgG4 characteristics in individuals with and without peach allergy, and Pru p 3-sIgE affinity in patients with different clinical symptoms.MethodsFifteen healthy controls and 32 peach-allergy patients were enrolled. sIgE, sIgG1, and sIgG4 to 5 Escherichia coli-expressed peach-allergen components were determined by enzyme-linked immunosorbent assays. Pru p 3-sIgE affinity was measured in Pru p 3-sIgE-positive patients, using immunoadsorbance.ResultsPatients were divided into oral allergy syndrome (OAS) and peach-induced anaphylaxis (PIA) groups. Serum Pru p 1-, Pru p 2-, Pru p 3-, Pru p 4-, and Pru p 7-sIgG1s were detected. Pru p 1- and Pru p 2-sIgG1 levels were higher in healthy controls, but Pru p 3-sIgG1 levels were significantly higher in peach-allergy patients. Pru p 1-, Pru p 3-, and Pru p 4-sIgG4-positivity was significantly greater among patients than among controls. Pru p 3 was the predominant allergen in peach-allergy patients. Allergen-sIgG1 and sIgG4 were similar between OAS and PIA patients. Pru p 3-sIgE levels were significantly higher in PIA patients, but Pru p 3-sIgE-positivity was similar in both groups. In Pru p 3-sIgE-positive patients, Pru p 3-sIgE affinity was significantly higher in PIA than OAS patients.ConclusionsAllergen-sIgG1 was associated with allergen exposure. Both Pru p 3-sIgE levels and affinity are key factors in severe peach-allergy patients.

Pollen-food allergy syndrome is an IgE-mediated allergic reaction arising from cross-reactive homologous allergens found in both food and pollen. Allergens, such as pathogenesis-related protein class 10 and profilin, usually trigger oropharyngeal itching and numbness in patients, whereas lipid transfer proteins tend to induce anaphylaxis. This article presents a case study of an individual with Artemisia pollen allergy who experienced anaphylaxis after consuming red fruit ginseng, a perennial herb belonging to the Campanulaceae family. This study revealed a novel allergen component mediating cross-allergy between Artemisia pollen and food, fructose-bisphosphate aldolase, which has not been documented in the literature concerning the pollen-food allergy syndrome. Fructose-bisphosphate aldolase tends to induce anaphylaxis in patients with Artemisia pollen-allergy and warrants clinicians' attention.

BackgroundAllergic airway disease (AAD) is a chronic disease characterized by airway inflammation, bronchoconstriction, and hyperresponsiveness. Although exogenous interleukin-10 (IL-10) alleviates allergic inflammation, it has a short half-life in vivo. Cell membrane-coated nanomaterials have been shown to protect therapeutic payloads and increase therapeutic efficacy. ObjectiveThis study was aimed at investigating the efficacy of a novel macrophage-based nanoparticle drug for the treatment of house dust mite (HDM)-induced allergic airway diseases. MethodsIL-10-poly (lactic-co-glycolic acid (PLGA) nanoparticles were encapsulated in alveolar macrophage cell membranes. An allergic airway disease mouse model was established by repeated inhalation of HDM extracts. The mice were treated with free IL-10, IL-10-PLGA nanoparticles (IL10-NP), or IL-10-alveolar macrophage cell membrane-coated nanoparticles (IL10-AMNP). The therapeutic effects were evaluated by measuring airway hyperresponsiveness, lung inflammation, cytokine levels, and regulatory T cells (Treg)- T-helper 17 (Th17) cell balance. ResultsCompared to free IL-10, IL10-AMNP significantly reduced airway hyperresponsiveness and T-helper 2 (Th2)/Th17 cytokines and inhibited neutrophilia and eosinophilia recruitment into the airways of HDM-induced mouse models. Additionally, the balance between Tregs and Th17 cells was significantly improved in groups treated with IL10-AMNP. ConclusionThis study demonstrated that PLGA nanoparticle cores coated with alveolar macrophage cell membranes can effectively deliver therapeutic cytokines to the lungs and improve the homeostatic balance between Tregs and Th17 cells. These findings suggest that macrophage-based nanoparticle drugs represent a promising approach for treating allergic airway diseases.

Background: The efficacy of allergen-specific subcutaneousimmunotherapy (SCIT) with Alt a 1 of the fungus A. alternata is still unknown. Yet, few studies compare the therapeutic effects and immunological mechanisms of Alt a 1 and A. alternata extracts. We aim to explore and compare the changes in allergic inflammation and immunological mechanisms of Alt a 1 and A. alternata in mice.Methods: Female BALB/c mice administrated recombinant Alt a 1 (rAlt a 1), native Alt a 1 (nAlt a 1), and A. alternata. Lung histology, airway hyper-reactivity (AHR), bronchoalveolar lavage fluid (BALF) cytokine levels, serum immunoglobulin responses, the expression of Bcl-6, the percentages of T follicular helper cells (Tfh), cytokine-related Tfh subtypes, regulatory B cells (Breg), and IL-10+ Breg cells were detected.Results: High-purity nAlt 1 protein was obtained. SCIT with Alt a 1 and Alternaria decreased airway and lung inflammation, including improvement of lung pathology, lower levels of AHR, reduction of total cell numbers, and IL-4 and IL-13 levels in BALF. Furthermore, Alt a 1-SCIT effectively suppressed the IgE responses, elevated IgG titers, and was superior in decreasing the expression of Bcl-6. Additionally, Alternaria-SCIT significantly decreased the expression of Tfh cells, L-4+ Tfh, and IL-5+ Tfh cells in the spleen, whereas Alt a 1 showed superior therapeutic effects in the lymph node. IL-13+ Tfh cells in these two treatment groups not being significant. IL 17A+ Tfh cells were alleviated most effectively after A. alternata-SCIT in both the spleen and lymph node. Intriguingly, IL-10+ Breg cells decreased remarkably in response to SCIT with rAlt a 1.Conclusions: Treatments with Alt a 1 and A. alternata extracts had beneficial effects on allergic inflammation. Alt a 1-SCIT resulted in prominent improvement in the immunoglobulin responses, Bcl-6, and IL-10+ Breg cells. Alternaria-SCIT was more likely to suppress the expression of Tfh and cytokine-related Tfh subtypes.

目的 探讨多发性大动脉炎患者生活质量现状及其影响因素,为提高患者的健康生活质量提供参考.方法 单中心回顾性研究.根据北京医院多发性大动脉炎注册研究(ChiCTR1800018752)数据库中的资料,对 2016 年 10 月至 2021 年 12 月的多发性大动脉炎患者进行健康问卷调查.问卷内容包括一般资料、疾病负担以及健康调查简表(SF-36)、欧洲五维健康量表(EQ-5D-5L)两种普适性生活质量量表.采用 Cronbach's α系数和 Spearman-Brown 系数分别评价SF-36 量表的内部一致性和分半信度.采用Spearman相关分析或非参数检验分析生活质量的影响因素.结果 共发放问卷 120 份,回收有效问卷 112 份,问卷有效回收率为 93.3%.SF-36 量表总体Cronbach's α系数为 0.87,多发性大动脉炎患者在一般健康状况(55.11±21.63)、精力(61.56±20.94)及精神健康(64.64±21.11)维度得分较低.EQ-5D-5L的视觉模拟标尺得分 76.07±20.50,效用指数得分 0.86±0.16.头臂型(P<0.01)和广泛型(P<0.01)多发性大动脉炎患者的生活质量得分较胸腹主动脉型低.生活质量各维度得分与多发性大动脉炎症状数量呈负相关(P<0.01),但未发现与性别、年龄、并发症数量、患病年龄、患病时长和手术次数相关.结论 SF-36 量表评估多发性大动脉炎患者生活质量具有较好的信度.多发性大动脉炎对患者的躯体健康和精神健康均产生显著影响.疾病分型和症状数量是影响患者生活质量的因素.

Background Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a serious and potentially life-threatening form of wheat allergy. Further episodes can only be prevented by avoiding wheat ingestion or avoiding exercise after wheat intake. Anaphylaxis may recur in some patients post-diagnosis. This study aimed to analyze the clinical features and management/outcomes of WDEIA in China. Methods We retrospectively analyzed the clinical characteristics, and laboratory testing of 197 patients with WDEIA. After diagnosis, the patients were followed up as outpatients to evaluate dietary/exercise choice and clinical outcomes. Results Among the 197 WDEIA patients (median age, 37 years), 53.8% were male and 28.4% had other allergic disorders. The median duration of anaphylaxis before diagnosis was 16 months. Significant delays in diagnosis (> 1 years) were recorded in 52.7% of the patients, which has not decreased by years ( P = 0.064). Exercise (83.8%), alcohol (12.2%), and nonsteroidal anti-inflammatory drugs (7.1%) were the most common cofactors. The most common clinical features were urticaria (100%), loss of consciousness (82.7%), dyspnea (50.8%), and hypotension (47.2%). Of the 197 eligible patients, 155 responded (78.7%), and 124 (80.0%) of which had no anaphylaxis post-diagnosis. A wheat-free diet prevented future anaphylaxis in 91.7% of the patients, followed by the avoidance of wheat combined with exercise (87%) and reduced wheat intake combined with exercise avoidance (80.5%). Conclusion The diagnosis of WDEIA is frequently delayed. Therefore, when patients present with unexplained anaphylaxis, the possibility of WDEIA should be considered. A wheat-free diet or avoiding wheat combined with exercise or reduced wheat combined with exercise avoidance helps to significantly reduce the onset of future anaphylaxis. However, approximately one-fifth of patients continue to experience anaphylaxis post-diagnosis. Thus, these patients must always carry epinephrine autoinjectors.

Purpose: Pollen from trees, grasses, and weeds is a common allergen source. The characteristics of pollen allergy in China are obviously different from Europe. Most studies have focused on tree and weed pollen, but there is a paucity of data on grass pollen sensitisation in China. Therefore, we used component-resolved diagnostics to investigate the serum-specific immunoglobulin E (sIgE) to grass pollen in Chinese patients with pollinosis. Methods: We retrospectively analysed 547 patients with pollen allegy from an outpatient Allergy Department in Beijing, China. All the patients answered questionnaires about their clinical allergy histories. Total immunoglobulin E (IgE) and sIgE levels to grass pollen (Bermuda, Timothy grass) were quantified by ImmunoCAP using 0.35 kUA/L as a threshold for positivity. Results: Of the 547 pollinosis patients, 389 (71.1%) showed a positive sIgE reaction to either grass pollen, or both. The prevalence of food allergy was significantly lower in patients with grass pollen sensitisation. Among the 389 patients with grass pollen sensitisation, the prevalence of sIgE to allergen extracts of bermuda, mugwort, ragweed, plane, hop, ash, birch, and timothy grass was 97%, 96%, 94%, 88%, 88%, 84%, 78%, and 78%, respectively. However, only 134/389 (34%) were positive for Cyn d 1, 29/389 (7%) for Phl p 1, and 8/389 (2%) for Phl p 5b. For pollinosis patients, 62/547 (11%) were sIgE-positive for cross-reactive carbohydrate determinants (CCDs), and their grass pollen-sIgE was also positive. Conclusions: The prevalence of in vitro IgE sensitisation to grass pollen extract is high in Chinese patients with pollinosis. But mostly spurious and characterized by IgE sensitisation to profilins and CCD, induced by other pollen. Component-resolved diagnostics is an extremely useful tool precise diagnostics of pollen allergy in China.

由中国医师协会、中国医师协会变态反应医师分会(以下简称分会)主办的"中国医师协会第五届变态反应医师分会年会(CCAA2021)"于2021年12月17日至19日以线上线下相结合形式召开.目前疫情虽尚未结束,但分会推广变态反应专科建设、过敏专科医生培训体系建设的脚步没有停下,在尹佳会长的领导下,分会为全国同道精心准备了一场学术盛宴,同时创造了安全而高效的学习、交流渠道.

食物过敏是一种由食物变应原引起的异常免疫反应.食物过敏的发生和发展是遗传因素与环境因素的共同作用,其中环境因素发挥重要作用,但其发病机制尚不明确.多项研究表明,肠道菌群与食物过敏的发生和发展密切相关,肠道菌群失衡可通过增强Th2型免疫应答,干扰免疫成熟,减少Treg细胞,破坏肠道黏膜屏障等机制导致机体出现食物过敏.本文针对肠道菌群紊乱与食物过敏的关系及其潜在机制进行综述,为食物过敏的早期预防及病因治疗提供依据.

Alternaria sensitization is correlated with persistent asthma. Type 2 (T2)-asthma endotypes are characterized by the release of eosinophils. However, the prevalence and sensitization patterns in patients with Alternaria asthma between T2-high and T2-low endotypes are unknown. We retrospectively reviewed 582 patients with Alternaria asthma and divided them into T2-high (n = 376) and T2-low (n = 206) groups with a threshold of 300 cells/mu L in blood eosinophil counts. Data for basic information, skin test or IgE detection results, and blood eosinophil counts were collected. The age of patients in the T2-high group (13.66 +/- 13.23) was lower than that of the T2low group (18.02 +/- 15.03). Patients with T2-high asthma had relatively higher rates of taking inhaled corticosteroids (ICS) and positive family history than the T2-low group. Pet keepers and allergen immunotherapy (AIT) patients were comparable between these groups, In the T2-high group, patients had higher levels of total serum IgE (T-IgE) and showed a significant positive correlation with eosinophil counts (r = 0.166, P = 0.001), followed by higher Alternaria-specific IgE (sIgE) levels (median, 13.7; range, 4.86-25.3). Compared to the T2-low group, the frequency of poly-sensitized patients and the rate of each allergen among the nine common allergens were all higher in the T2-high group; the statistical differences mainly focused on pollens such as birch (P = 0.005), firmiana (P = 0.004), and mugwort (P = 0.005). Young, male patients had a high prevalence of T2-high Alternaria asthma, along with higher rates of T-IgE, sIgE levels, and poly-sensitized patterns.

Purpose: Royal jelly and honeycomb are commonly consumed in China, and anaphylaxis caused by ingestion of royal jelly is rare. To date, there is no report of anaphylaxis after ingestion of royal jelly in China. Its cross-reactivity with honeycomb is still unclear. Case Report: A 56-year-old Chinese female experienced two episodes of anaphylaxis within 1 hour after ingestion of royal jelly within one month. After avoiding royal jelly and other bee products, no anaphylactic reaction occurred again. The skin prick test and basophil activation test showed positive reactivity to royal jelly and honeycomb. In immunoblotting and immunoblotting inhibition tests, a 60 kDa protein was recognized in royal jelly and cross-reactivity with honeycomb. The mass spectrometry data revealed that the 62kDa protein belongs to major royal jelly protein 3. Conclusion: Our data suggest that major royal jelly protein 3 of royal jelly is a main allergen that induces anaphylaxis and cross-reactivity with honeycomb. Therefore, the patient was allergic to royal jelly to avoid other bee products.