Metabolomics identifies phenotypic biomarkers of amino acid metabolism in milk allergy and sensitized tolerance.

BACKGROUND: A substantial proportion of sensitized individuals tolerate suspected foods without developing allergic symptoms; this phenomenon is known as sensitized tolerance. The immunogenic and metabolic features underlying the sensitized-tolerant phenotype remain largely unknown. OBJECTIVE: We aimed to uncover the metabolic signatures associated with clinical milk allergy (MA) and sensitized tolerance using metabolomics. METHODS: We characterized the serum metabolic and immunologic profiles of children with clinical IgE-mediated MA (n = 30) or milk-sensitized tolerance (n = 20) and healthy controls (n = 21). A comparative analysis was performed to identify dysregulated pathways associated with the clinical manifestations of food allergy. We also analyzed specific biomarkers indicative of different sensitization phenotypes in children with MA. The candidate metabolites were validated in an independent quantification cohort (n = 41). RESULTS: Metabolomic profiling confirmed the presence of a distinct metabolic signature that discriminated children with MA from those with milk-sensitized tolerance. Amino acid metabolites generated via arginine, proline, and glutathione metabolism were uniquely altered in children with sensitized tolerance. Arginine depletion and metabolism through the polyamine pathway to fuel glutamate synthesis were closely associated with suppression of clinical symptoms in the presence of allergen-specific IgE. In children with MA, the polysensitized state was characterized by disturbances in tryptophan metabolism. CONCLUSIONS: By combining untargeted metabolomics with targeted validation in an independent quantification cohort, we identified candidate metabolites as phenotypic and diagnostic biomarkers of food allergy. Our results provide insights into the pathologic mechanisms underlying childhood allergy and suggest potential therapeutic targets.

Identification, Characterization, Cloning, and Cross-Reactivity of Zan b 2, a Novel Pepper Allergen of 11S Legumin.

Protein from Sichuan peppers can elicit mild to severe allergic reactions. However, little is known about their allergenic proteins. We aimed to isolate, identify, clone, and characterize Sichuan pepper allergens and to determine its allergenicity and cross-reactivities. Sichuan pepper seed proteins were extracted and then analyzed by SDS-PAGE. Western blotting was performed with sera from Sichuan pepper-allergic individuals. Proteins of interest were purified using hydrophobic interaction chromatography and gel filtration and further analyzed by analytical ultracentrifugation, circular dichroism spectroscopy, and mass spectrometry (MS). Their coding region was amplified in the genome. IgE reactivity and cross-reactivity of allergens were evaluated by dot blot, enzyme-linked immunosorbent assay (ELISA), and competitive ELISA. Western blot showed IgE binding to a 55 kDa protein. This protein was homologous to the citrus proteins and has high stability and a sheet structure. Four DNA sequences were cloned. Six patients' sera (60%) showed specific IgE reactivity to this purified 11S protein, which was proved to have cross-reactivation with extracts of cashew nuts, pistachios, and citrus seeds. A novel allergen in Sichuan pepper seeds, Zan b 2, which belongs to the 11S globulin family, was isolated and identified. Its cross-reactivity with cashew nuts, pistachios, and citrus seeds was demonstrated.

Genetic Polymorphisms of GP1BA, PEAR1, and PAI-1 May Be Associated with Serum sIgE and Blood Eosinophil Levels in Chinese Patients with Allergic Diseases.

BACKGROUND: It has been suggested that genetic factors may be substantially linked to allergy disorders. OBJECTIVE: This study aims to investigate the relationship between the serum specific Immunoglobulin E [sIgE], blood eosinophil, and the polymorphisms of glycoprotein Ib alpha gene [GP1BA] rs6065, platelet endothelial aggregation receptor 1 gene [PEAR1] rs12041331, and plasminogen activator inhibitor 1 gene [PAI-1] rs1799762. METHODS: From the Peking Union Medical College Hospital, this study enrolled 60 healthy participants and 283 participants with allergic diseases. TaqMan-minor groove binder [MGB] quantitative polymerase chain reaction [qPCR] was used to examine the gene polymorphisms in each group. RESULTS: The TaqMan-MGB qPCR results were completely consistent with the DNA sequencing results, according to other studies in this medical center [Kappa =1, p <0.001]. The GP1BA rs6065, PEAR1 rs12041331, and PAI-1 rs1799762 polymorphisms did not show different distribution between allergy patients and healthy individuals. Concerning allergy patients, the CT [n=33] genotype of GP1BA rs6065 had higher blood eosinophil level than the CC [n=250] genotype [0.59, IQR 0.32-0.72 vs 0.31, IQR 0.15-0.61, *109/L, p =0.005]. The serum sIgE of AA [n=46] genotype of PEAR1 rs12041331 was lower [median 3.7, interquartile quartiles [IQR] 0.2-16.8, kU/L] than the GA [n=136] and GG [n=101] genotypes [GA median 16.3, IQR 3.1-46.3, kU/L, p = 0.002; GG median 12.9, IQR 3.0-46.9, kU/L, p =0.003]. The GA genotypes of PEAR1 rs12041331were with higher blood eosinophil levels [median 0.42, IQR 0.17-0.74 *109/L] than the AA genotype [median 0.25, IQR 0.15-0.41*109/L, p =0.012]. The sIgE of the 5G5G [n=44] genotype of PAI-1 rs1799762 was lower [median 5.0, IQR 0.1-22.8, kU/L] than the 4G5G [n=144] [median 17.3, IQR 3.7-46.0, kU/L, p = 0.012]. CONCLUSION: The GP1BA rs6065, PEAR1 rs12041331, and PAI-1 rs1799762 polymorphisms may be associated with the genetic susceptibility of serum sIgE or blood eosinophil in Chinese allergic disease patients.

Artificial intelligence-driven design of the assembled major cat allergen Fel d 1 to improve its spatial folding and IgE-reactivity.

BACKGROUND: Cat-derived allergens are considered as one of the most common causes of allergic diseases worldwide. Fel d 1 is a major cat allergen and plays an important role in immunoglobulin E (IgE)-reaction diagnosis. However, the two separate chains of Fel d 1 exhibited lower IgE-reactivity than its complete molecule of an assembled form, which makes it difficult to efficiently prepare and limits the application of Fel d 1 in molecular diagnosis of cat allergy. METHODS: We first applied artificial intelligence (AI) based tool AlphaFold2 to build the 3-dimensional structures of Fel d 1 with different connection modes between two chains, which were evaluated by ERRAT program and were expressed in Escherichia coli. We then calculated the expression ratios of soluble form/inclusion bodies form of optimized Fel d 1. The Circular Dichroism (CD), High Performance Liquid Chromatography-Size Exclusion Chromatography (HPLC-SEC) and reducing/non-reducing SDS-PAGE were performed to characterize the folding status and dimerization of the optimized fusion Fel d 1. The improvement of specific-IgE reactivity to optimized fusion Fel d 1 was investigated by enzyme linked immunosorbent assay (ELISA). RESULTS: Among several linkers, 2 × GGGGS got the highest scores, with an overall quality factor of 100. The error value of the residues around the junction of 2 × GGGGS was lower than others. It exhibited highest proportion of soluble protein than other Fel d 1 constructs with ERRAT (GGGGS, KK as well as direct fusion Fel d 1). The results of CD and HPLC-SEC showed the consistent folding and dimerization of two fused subunits between the optimized fusion Fel d 1 and previously well-defined direct fusion Fel d 1. The overall IgE-binding absorbance of optimized fusion Fel d 1 tested by ELISA was improved compared with that of the direct fusion Fel d 1. CONCLUSION: We firstly provided an AI-design strategy to optimize the Fel d 1, which could spontaneously fold into its native-like structure without additional refolding process or eukaryotic folding factors. The improved IgE-binding activity and simplified preparation method could greatly facilitate it to be a robust allergen material for molecular diagnosis of cat allergy.

Identification of Pla a 7 as a novel pollen allergen group in Platanus acerifolia pollen.

BACKGROUND: Platanus acerifolia is recognized as a source of allergenic pollen worldwide. Currently, five Platanus acerifolia pollen allergens belonging to different protein families have been identified, in which profilin and enolase were characterized by our group recently. Besides, we also screened and identified a novel allergen candidate as triosephosphate isomerase, which was different from already known types of pollen allergens. However, the role of this novel allergen group in Platanus acerifolia pollen allergy was unclear. Therefore, we further investigated the allergenicity and clarify its clinical relevance in this study. METHODS: The natural triosephosphate isomerase from Platanus acerifolia pollen was purified by three steps of chromatography and identified by mass spectrometry. The cDNA sequence of this protein was matched from in-house transcripts based on internal peptide sequences, which was further confirmed by PCR cloning. The recombinant triosephosphate isomerase was expressed and purified from E. coli. Allergenicity analysis of this protein was carried out by enzyme linked immunosorbent assay, immunoblot, and basophil activation test. RESULTS: A novel allergen group belonging to triosephosphate isomerase was firstly identified in Platanus acerifolia pollen and named as Pla a 7. The cDNA of Pla a 7 contained an open reading frame of 762 bp encoding 253 amino acids. The natural Pla a 7 displayed 41.4% IgE reactivity with the patients' sera by ELISA, in which the absorbance value showed correlation to the serum sIgE against Platanus acerifolia pollen extract. Inhibition of IgE-binding to pollen extracts reached 26%-94% in different Pla a 7-positive sera. The recombinant Pla a 7 exhibited weaker IgE-reactivity in ELISA than its natural form, but showed comparable activity in immunoblot. The allergenicity was further confirmed by basophil activation test. CONCLUSIONS: Triosephosphate isomerase (Pla a 7) was first recognized as pollen allergen in Platanus acerifolia pollen, which is a completely different type of pollen allergen from those previously reported. This finding is essential to enrich information on allergen components and pave the way for molecular diagnosis or treatment strategies for Platanus acerifolia pollen allergy.

HMGN2 and Histone H1.2: potential targets of a novel probiotic mixture for seasonal allergic rhinitis.

Background: Allergic rhinitis (AR) is a common nasal inflammatory disorder that severely affects an individual's quality of life (QoL) and poses a heavy financial burden. In addition to routine treatments, probiotic intervention has emerged as a promising strategy for preventing and alleviating allergic diseases. The main objective of this study was to determine the effect of a novel multi-strain probiotic mixture on AR symptoms and investigate potential targets underlying the probiotic intervention. Methods: A randomized, double-blind, placebo-controlled clinical study was conducted on AR patients who were allergic to autumnal pollens (n = 31). Placebo or a novel probiotic mixture, composed of Lactobacillus rhamnosus (L. rhamnosus) HN001, L. acidophilus NCFM, Bifidobacterium lactis (B. lactis) Bi-07, L. paracasei LPC-37, and L. reuteri LE16, was administered after 2 months. The therapeutic efficacy was evaluated by a symptom assessment scale. Before and during the pollen season, blood samples were collected, and peripheral blood mononuclear cells (PBMCs) were isolated for further tandem mass tags (TMTs)-based quantitative proteomic analyses. Potential targets and underlying pathological pathways were explored using bioinformatics methods. Results: During the pollen season, the rhinoconjunctivitis symptom score of participants who were administered probiotics (probiotic group, n = 15) was significantly lower than those administered placebo (placebo group, n = 15) (P = 0.037). The proteomic analyses identified 60 differentially expressed proteins (DEPs) in the placebo group, and subsequent enrichment analyses enriched a series of pathways and biological processes, including signaling pathways of inflammation, coagulation cascade, lipid, carbohydrate and amino acid metabolic pathways, and transcription and translation processes. Least Absolute Shrinkage and Selection Operator (LASSO) regression extracted five main elements, namely, GSTO1, ATP2A2, MCM7, PROS1, and TRIM58, as signature proteins. A total of 17 DEPs were identified in the probiotic group, and there was no pathway enriched. Comparison of DEPs in the two groups revealed that the expression levels of the high-mobility group nucleosome-binding domain-containing protein 2 (HMGN2) and Histone H1.2 presented an opposite trend with different interventions. Conclusion: Our data showed that AR symptoms alleviated after treatment with the novel multi-strain probiotic mixture, and the proteomic analyses suggested that HMGN2 and Histone H1.2 might be targets of probiotic intervention for seasonal AR.

Early-life risk factors for food allergy: Dietary and environmental factors revisited.

There appears a steep increase in the prevalence of food allergy worldwide in the past few decades. It is believed that, rather than genetic factors, the recently altered dietary and environmental factors are the driving forces behind the rapid increase of this disease. Accumulating evidence has implied that external exposures that occurred in prenatal and postnatal periods could affect the development of oral tolerance in later life. Understanding the potential risk factors for food allergy would greatly benefit the progress of intervention and therapy. In this review, we present updated knowledge on the dietary and environmental risk factors in early life that have been shown to impact the development of food allergy. These predominantly include dietary habits, microbial exposures, allergen exposure routes, environmental pollutants, and so on. The key evidence, conflicts, and potential research topics of each theory are discussed, and associated interventional strategies to prevent the disease development and ameliorate treatment burden are included. Accumulating evidence has supported the causative role of certain dietary and environmental factors in the establishment of oral tolerance in early life, especially the time of introducing allergenic foods, skin barrier function, and microbial exposures. In addition to certain immunomodulatory factors, increasing interest is raised toward modern dietary patterns, where adequately powered studies are required to identify contributions of those modifiable risk factors. This review broadens our understanding of the connections between diet, environment, and early-life immunity, thus benefiting the progress of intervention and therapy of food allergy.

Serological analysis of allergic components of house dust mite provides more insight in epidemiological characteristics and clinical symptom development in North China.

Background: House dust mite (HDM) is the most common airborne source causing complex allergy symptoms. There are geographic differences in the allergen molecule sensitization profiles. Serological testing with allergen components may provide more clues for diagnosis and clinical management. Objective: This study aims to investigate the sensitization profile of eight HDM allergen components in a large number of patients enrolled in the clinic and to analyze the relation of gender, age, and clinical symptoms in North China. Methods: The 548 serum samples of HDM-allergic patients (ImmunoCAP® d1 or d2 IgE ≥0.35) were collected in Beijing City and divided in four different age groups and three allergic symptoms. The specific IgE of HDM allergenic components, Der p 1/Der f 1, Der p 2/Der f 2, Der p 7, Der p 10, Der p 21, and Der p 23, was measured using the micro-arrayed allergen test kit developed by Hangzhou Zheda Dixun Biological Gene Engineering Co., Ltd. The new system was validated by comparing to single-component Der p 1, Der p 2, and Der p 23 tests by ImmunoCAP in 39 sera. The epidemiological study of these IgE profiles and the relation to age and clinical phenotypes were analyzed. Results: A greater proportion of male patients was in the younger age groups, while more female patients were in the adult groups. Both the sIgE levels and the positive rates (approximately 60%) against Der p 1/Der f 1 and Der p 2/Der f 2 were higher than for the Der p 7, Der p 10, and Der p 21 components (below 25%). The Der f 1 and Der p 2 positive rates were higher in 2-12-year-old children. The Der p 2 and Der f 2 IgE levels and positive rates were higher in the allergic rhinitis group. The positive rates of Der p 10 increased significantly with age. Der p 21 is relevant in allergic dermatitis symptom, while Der p 23 contributes to asthma development. Conclusion: HDM groups 1 and 2 were the major sensitizing allergens, with group 2 being the most important component relevant to respiratory symptoms in North China. The Der p 10 sensitization tends to increase with age. Der p 21 and Der p 23 might be associated with the development of allergic skin disease and asthma, respectively. Multiple allergen sensitizations increased the risk of allergic asthma.

Progress of metabolomics in atopic dermatitis: a systematic review.

Atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by recurrent eczema and intense pruritus, is a major skin-related burden worldwide. The diagnosis and treatment of AD is often challenging due to the high heterogeneity of AD, and its exact etiology is unknown. Metabolomics offers the opportunity to follow continuous physiological and pathological changes in individuals, which allows accurate diagnosis and management as well as providing deep insights into the etiopathogenesis of AD. Several metabolomic studies of AD have been published over the past few years. The aim of this review is to summarize these findings and help researchers to understand the rapid development of metabolomics for AD. A comprehensive and systematic search was performed using the PubMed, Embase, Cochrane Library and Web of Science databases. Twenty-six papers were finally included in the review after quality assessment. Significant differences in metabolite profiles were found between patients with AD and healthy individuals. This study provides a comprehensive overview of metabolomic research in AD. A better understanding of the metabolomics of AD may offer novel diagnostic, prognostic, and therapeutic approaches.

The 4G/5G polymorphism of plasminogen activator inhibitor type 1 is a predictor of allergic cough.

Background: It has been suggested that genetic factors may be substantially linked to allergy disorders. This study aims to investigate the relationship between the genetic susceptibility of Chinese patients with allergy disorders and the polymorphisms of plasminogen activator inhibitor 1 gene (PAI-1) rs1799762, cysteinyl leukotriene receptor 1 gene (CYSLTR1) rs320995, gasdermin B gene (GSDMB) rs7216389, glycoprotein IIIa gene (GPIIIa) rs5918, glycoprotein Ib alpha gene (GP1BA) rs6065, platelet endothelial aggregation receptor 1 gene (PEAR1) rs12041331, and tumor necrosis factor alpha gene (TNF-α) rs1800629. Methods: From the Peking Union Medical College Hospital, this study enrolled 60 healthy participants and 286 participants with allergic diseases. TaqMan-minor groove binder (MGB) quantitative polymerase chain reaction (qPCR) was used to examine the gene polymorphisms in each group. Results: The TaqMan-MGB qPCR results were completely consistent with the DNA sequencing results, according to other studies in this medical center (Kappa = 1, p < .001). Only the distribution of PAI-1 rs1799762 was different between patients with allergic cough and healthy people (χ2 = 7.48, p = .0238). With regard to cough patients, the 4G4G and 5G5G genotypes were more frequent (allergic cough vs. healthy individuals: 4G4G 57.9% vs. 26.7%; 5G5G 20.0% vs. 13.3%), but the 4G5G genotype was more frequent in healthy people (allergic cough vs. healthy individuals: 45.7% vs. 60.0%). The CYSLTR1 rs320995, GSDMB rs7216389, GPIIIa rs5918, GP1BA rs6065, PEAR1 rs12041331, and TNF-α rs1800629 polymorphisms, however, did not show any of such relationships. Conclusion: The PAI-1 rs1799762 polymorphisms may be associated with the genetic susceptibility of Chinese allergic disease patients with cough performance.

Structures and Anti-Allergic Activities of Natural Products from Marine Organisms.

In recent years, allergic diseases have occurred frequently, affecting more than 20% of the global population. The current first-line treatment of anti-allergic drugs mainly includes topical corticosteroids, as well as adjuvant treatment of antihistamine drugs, which have adverse side effects and drug resistance after long-term use. Therefore, it is essential to find alternative anti-allergic agents from natural products. High pressure, low temperature, and low/lack of light lead to highly functionalized and diverse functional natural products in the marine environment. This review summarizes the information on anti-allergic secondary metabolites with a variety of chemical structures such as polyphenols, alkaloids, terpenoids, steroids, and peptides, obtained mainly from fungi, bacteria, macroalgae, sponges, mollusks, and fish. Molecular docking simulation is applied by MOE to further reveal the potential mechanism for some representative marine anti-allergic natural products to target the H1 receptor. This review may not only provide insight into information about the structures and anti-allergic activities of natural products from marine organisms but also provides a valuable reference for marine natural products with immunomodulatory activities.

Treatment of allergy: Overview of synthetic anti-allergy small molecules in medicinal chemistry.

The prevalence of allergic diseases has been continuously increasing over the past few decades, affecting approximately 20-30% of the global population. Allergic reactions to infection of respiratory tract, digestive tract, and skin system involve multiple different targets. The main difficulty of anti-allergy research is how to develop drugs with good curative effect and less side effects by adopting new multi-targets and mechanisms according to the clinical characteristics of different allergic populations and different allergens. This review focuses on information concerning potential therapeutic targets as well as the synthetic anti-allergy small molecules with respect to their medicinal chemistry. The structure-activity relationship and the mechanism of compound-target interaction were highlighted with perspective to histamine-1/4 receptor antagonists, leukotriene biosynthesis, Th2 cytokines inhibitors, and calcium channel blockers. We hope that the study of chemical scaffold modification and optimization for different lead compounds summarized in this review not only lays the foundation for improvement of success rate and efficiency of virtual screening of antiallergic drugs, but also can provide valuable reference for the drug design of related promising research such as allergy, inflammation, and cancer.

Impact of Air Pollution on Atopic Dermatitis: A Comprehensive Review.

Air pollution is associated with multiple health problems worldwide, contributing to increased morbidity and mortality. Atopic dermatitis (AD) is a common allergic disease, and increasing evidence has revealed a role of air pollution in the development of atopic dermatitis. Air pollutants are derived from several sources, including harmful gases such as nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO), as well as particulate matter (PM) of various sizes, and bioaerosols. Possible mechanisms linking air pollution to atopic dermatitis include damage to the skin barrier through oxidative stress, increased water loss, physicochemical injury, and an effect on skin microflora. Furthermore, oxidative stress triggers immune dysregulation, leading to enhanced sensitization to allergens. There have been multiple studies focusing on the association between various types of air pollutants and atopic dermatitis. Since there are many confounders in the current research, such as climate, synergistic effects of mixed pollutants, and diversity of study population, it is not surprising that inconsistencies exist between different studies regarding AD and air pollution. Still, it is generally accepted that air pollution is a risk factor for AD. Future studies should focus on how air pollution leads to AD as well as effective intervention measures.

Identification and characterization of natural PR-1 protein as major allergen from Humulus japonicus pollen.

BACKGROUND: The Humulus japonicus pollen is one of the most common allergenic pollens in China. However, little is unveiled regarding the allergenic components in Humulus japonicus pollen. Our study aimed to purify and identify the pathogenesis-related 1 (PR-1) protein from Humulus japonicus pollen, and to characterize the molecular and immunochemical properties of this novel allergen. METHODS: The natural PR-1 protein (named as Hum j PR-1) was purified from Humulus japonicus pollen extracts with a combined strategy of chromatography, and identified by mass spectrometry. The coding sequence of Hum j PR-1 was confirmed by cDNA cloning. The recombinant Hum j PR-1 was expressed and purified from Escherichia coli. The allergenicity was assessed by immunoblot, enzyme-linked immunosorbent assay (ELISA), inhibition ELISA, and basophil activation test using Humulus japonicus allergic patients' whole blood. The physicochemical properties and 3-dimensional structure of it were comprehensively characterized by in silico methods. RESULTS: The allergenicity analysis revealed that 76.6 % (23/30) of the Humulus japonicus pollen allergic patients displayed specific IgE recognition of the natural Hum j PR-1. The cDNA sequence of Hum j PR-1 had a 516-bp open reading frame encoding 171 amino acids. Physicochemical analysis indicated that Hum j PR-1 was a stable and relatively thermostable protein. Hum j PR-1 shared a similar 3-dimensional folding pattern with other homologous allergens, which was a unique αßα sandwich structure containing 4 α-helices and 6 antiparallel ß-sheets, encompassing 4 conserved CAP domain. CONCLUSION: The natural PR-1 was firstly purified and characterized as a major allergenic allergen in Humulus japonicus pollen. These findings would contribute to developing diagnostic and therapeutic strategies for Humulus japonicus pollinosis.

The top 100 most cited articles in anaphylaxis: a bibliometric analysis.

Bibliometric analysis is helpful to determine the most influential studies in a specific field. A large number of publications in anaphylaxis have been published. However, no bibliometric analysis of anaphylaxis was conducted based on our known. The aim of this study is to identify the top 100 most cited articles in anaphylaxis and analyze their bibliometric characteristics. We searched in the Web of Science core database on November 20, 2021. Articles were listed in descending order by their total citations. Hence the top 100 most cited articles in anaphylaxis were identified and analyzed. Bibliometric indicators included: year of publication, total number of citations and average citations per year (ACY), journal of publication and impact factor (IF), countries, institutes, and authors, which were analyzed by Biblioshiny. Co-occurrence was used to visualize the classification and hotspots. The top 100 most cited articles were published between 1991 and 2017. The largest number of articles was published in a single interval in 2006-2008. Total citations of the 100 articles were between 155 and 1241 and were positively correlated with the number of articles published in each 3-year interval. The top100 articles were published in 34 different journals. The Journal of Allergy and Clinical Immunology published the most (n = 41). The corresponding authors of the top100 articles were from 13 different countries, mostly in North America and Europe. Statistical analysis revealed a positive correlation between total number of citations and ACY (r = 0.670, p < 0.01) and between total number of citations and IF (r = 0.219, p < 0.05), whereas a negative correlation between ACY and length of time since publication (r = - 0.697, p < 0.01). The research focuses were classified into three clusters: (1) the epidemiology and management. (2) the risk factor and treatment. (3) the assessment and diagnosis. COVID-19 vaccines, drug allergy and management were the recent major topics. This bibliometric analysis reveals the progress and hotspots of research in anaphylaxis, which may lay a foundation for further research.

The top 100 most cited articles in the last two decades of atopic dermatitis: A bibliometric analysis.

Background: Atopic dermatitis (AD) is the leading cause of skin-related disease burden worldwide, affecting a large percentage of the population. Bibliometrics is the statistical analysis of academic literature in a certain field. Objectives: We aimed to perform the latest bibliometric analysis of atopic dermatitis literature. Methods: We searched the Web of Science database on 29th Nov 2021. We used the keywords "atopic dermatitis," "atopic eczema," and "eczema" for our search. All items published between 2001 and 2021 were included. The top 100 most cited articles were identified and analyzed. Results: Our study provided a detailed bibliometric analysis of the top 100 most cited articles on atopic dermatitis. These articles were published between 2002 and 2019 and were from 15 different countries, mostly in the USA and Germany. Most articles have focused on the pathogenesis and treatment of AD. The Journal of Allergy and Clinical Immunology made the greatest contribution to the top 100 list, with 28 articles. The most cited article originated from Lancet. The highest number of citations was seen in 2006, with 9220 citations, while the highest number of publications was seen in 2006 with 12 publications. Conclusions: Our study aims to provide physicians and researchers with a historical perspective for the scientific progress of atopic dermatitis, and help clinicians effectively obtain useful articles that have a significant impact on the field of atopic dermatitis.

Diagnostic accuracy and safety of Dermatophagoides pteronyssinus extracts used for skin prick test.

BACKGROUND: Dermatophagoides pteronyssinus is a common allergen causing allergic diseases in China. The aim of this study was to evaluate the efficacy and safety of D. pteronyssinus extracts produced by Peking Union Medical College Hospital (PUMCH) for the skin prick test (SPT) in the diagnosis of D. pteronyssinus allergy. METHODS: A total of 910 subjects with allergic diseases were prescribed D. pteronyssinus SPT and specific sIgE (sIgE) test among the Outpatients of Department of Allergy, PUMCH from August 10, 2015 to August 30, 2017. Receiver operating characteristic curve (ROC) analysis was performed according to the results of D. pteronyssinus-sIgE detection. The accuracy of D. pteronyssinus extracts used for SPT in the diagnosis of D. pteronyssinus allergy was evaluated under different cutoff values. Adverse events after SPT were recorded to evaluate safety. RESULTS: There were 796 and 618 subjects in the full analysis set (FAS) and the per protocol set (PPS), respectively. The areas under the curve of FAS and PPS were 0.871 and 0.873, respectively. According to the ROC of PPS, the optimal and 95% specificity diagnostic cutoff values of D. pteronyssinus SPT mean wheal diameter were 3.25 and 3.75 mm, respectively. No adverse events occurred. CONCLUSION: The extracts of D. pteronyssinus for SPT were simple, highly accurate, and safe and should be considered for recommendation in the clinical diagnosis of D. pteronyssinus allergy.