Deciphering the omicron variant: integrated omics analysis reveals critical biomarkers and pathophysiological pathways.

BACKGROUND: The rapid emergence and global dissemination of the Omicron variant of SARS-CoV-2 have posed formidable challenges in public health. This scenario underscores the urgent need for an enhanced understanding of Omicron's pathophysiological mechanisms to guide clinical management and shape public health strategies. Our study is aimed at deciphering the intricate molecular mechanisms underlying Omicron infections, particularly focusing on the identification of specific biomarkers. METHODS: This investigation employed a robust and systematic approach, initially encompassing 15 Omicron-infected patients and an equal number of healthy controls, followed by a validation cohort of 20 individuals per group. The study's methodological framework included a comprehensive multi-omics analysis that integrated proteomics and metabolomics, augmented by extensive bioinformatics. Proteomic exploration was conducted via an advanced Ultra-High-Performance Liquid Chromatography (UHPLC) system linked with mass spectrometry. Concurrently, metabolomic profiling was executed using an Ultra-Performance Liquid Chromatography (UPLC) system. The bioinformatics component, fundamental to this research, entailed an exhaustive analysis of protein-protein interactions, pathway enrichment, and metabolic network dynamics, utilizing state-of-the-art tools such as the STRING database and Cytoscape software, ensuring a holistic interpretation of the data. RESULTS: Our proteomic inquiry identified eight notably dysregulated proteins (THBS1, ACTN1, ACTC1, POTEF, ACTB, TPM4, VCL, ICAM1) in individuals infected with the Omicron variant. These proteins play critical roles in essential physiological processes, especially within the coagulation cascade and hemostatic mechanisms, suggesting their significant involvement in the pathogenesis of Omicron infection. Complementing these proteomic insights, metabolomic analysis discerned 146 differentially expressed metabolites, intricately associated with pivotal metabolic pathways such as tryptophan metabolism, retinol metabolism, and steroid hormone biosynthesis. This comprehensive metabolic profiling sheds light on the systemic implications of Omicron infection, underscoring profound alterations in metabolic equilibrium. CONCLUSIONS: This study substantially enriches our comprehension of the physiological ramifications induced by the Omicron variant, with a particular emphasis on the pivotal roles of coagulation and platelet pathways in disease pathogenesis. The discovery of these specific biomarkers illuminates their potential as critical targets for diagnostic and therapeutic strategies, providing invaluable insights for the development of tailored treatments and enhancing patient care in the dynamic context of the ongoing pandemic.

SARS-CoV-2 neutralising antibody therapies: Recent advances and future challenges.

The COVID-19 pandemic represents an unparalleled global public health crisis. Despite concerted research endeavours, the repertoire of effective treatment options remains limited. However, neutralising-antibody-based therapies hold promise across an array of practices, encompassing the prophylaxis and management of acute infectious diseases. Presently, numerous investigations into COVID-19-neutralising antibodies are underway around the world, with some studies reaching clinical application stages. The advent of COVID-19-neutralising antibodies signifies the dawn of an innovative and promising strategy for treatment against SARS-CoV-2 variants. Comprehensively, our objective is to amalgamate contemporary understanding concerning antibodies targeting various regions, including receptor-binding domain (RBD), non-RBD, host cell targets, and cross-neutralising antibodies. Furthermore, we critically examine the prevailing scientific literature supporting neutralising antibody-based interventions, and also delve into the functional evaluation of antibodies, with a particular focus on in vitro (vivo) assays. Lastly, we identify and consider several pertinent challenges inherent to the realm of COVID-19-neutralising antibody-based treatments, offering insights into potential future directions for research and development.

Does environmental innovation have peer effects? The moderating role of slack resources and avoidance goal orientation.

Exploring the interactive patterns of environmental innovation behavior among firms is of great significance for improving the level of environmental innovation in the whole industry and achieving sustainable development. Based on social interaction theory, this study examines the peer effect of a firm's environmental innovation and the moderating effects of slack resources and avoidance goal orientation. A total of 1210 listed companies in China's manufacturing industry from 2015 to 2020 comprised the research sample, and the researchers used multiple regression analysis to analyze the data. The results indicate a peer effect of environmental innovation among firms; that is, firms' environmental innovation will positively impact the environmental innovation of other firms in the industry. Slack resources positively moderate the peer effect of environmental innovation among firms, and firms' avoidance goal orientation weakens that moderating effect. This study reveals the internal mechanism of the peer effect of environmental innovation and provides new management implications for managers' environmental-innovation decision-making.

Removing Negative Impacts from Inevitable Nonreproducible and Nonspecific Antibody-Probe Interactions in Viral Serology.

Serological assays are indispensable tools in public health. Presently deployed serological assays, however, largely overlook research progress made in the last two decades that jeopardizes the conceptual foundation of these assays, i.e., antibody (Ab) specificity. Challenges to traditional understanding of Ab specificity include Ab polyspecificity and most recently nonreproducible Ab-probe interactions (NRIs). Here, using SARS-CoV-2 and four common livestock viruses as a test bed, we developed a new serological platform that integrates recent understanding about Ab specificity. We first demonstrate that the response rate (RR) from a large-sized serum pool (∼100) is not affected by NRIs or by nonspecific Ab-probe interactions (NSIs), so RR can be incorporated into the diagnostic probe selection process. We subsequently used multiple probes (configured as a "protein peptide hybrid microarray", PPHM) to generate a digital microarray index (DMI) and finally demonstrated that DMI-based analysis yields an extremely robust probabilistic trend that enables accurate diagnosis of viral infection that overcomes multiple negative impacts exerted by NSI/NRI. Thus, our study with SARS-CoV-2 confirms that the PPHM-RR-DMI platform enables very rapid development of serological assays that outperform traditional assays (for both sensitivity and specificity) and supports that the platform is extendable to other viruses.

Integrative omics analysis identifies biomarkers of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by chronic progressive pulmonary fibrosis and a poor prognosis. Genetic studies, including transcriptomic and proteomics, have provided new insight into revealing mechanisms of IPF. Herein we provided a novel strategy to identify biomarkers by integrative analysis of transcriptomic and proteomic profiles of IPF patients. We examined the landscape of IPF patients' gene expression in the transcription and translation phases and investigated the expression and functions of two new potential biomarkers. Differentially expressed (DE) mRNAs were mainly enriched in pathways associated with immune system activities and inflammatory responses, while DE proteins are related to extracellular matrix production and wound repair. The upregulated genes in both phases are associated with wound repair and cell differentiation, while the downregulated genes in both phases are associated with reduced immune activities and the damage of the alveolar tissues. On this basis, we identified thirteen potential marker genes. Among them, we validated the expression changes of butyrophilin-like 9 (BTNL9) and plasmolipin (PLLP) and investigated their functional pathways in the IPF mechanism. Both genes are downregulated in the tissues of IPF patients and Bleomycin-induced mice, and co-expression analysis indicates that they have a protective effect by inhibiting extracellular matrix production and promoting wound repair in alveolar epithelial cells.

ERC-BiP Functional Protein Pathway for Assessing Endoplasmic Reticulum Stress Induced by SARS-CoV-2 Replication after Cell Invasion.

Background: SARS-CoV-2 induces apoptosis and amplifies the immune response by continuously stressing the endoplasmic reticulum (ER) after invading cells. This study aimed to establish a protein-metabolic pathway associated with ER dysfunction based on the invasion mechanism of SARS-CoV-2. Methods: This study included 17 healthy people and 46 COVID-19 patients, including 38 mild patients and 8 severe patients. Proteomics and metabolomics were measured in the patient plasma collected at admission and one week after admission. The patients were further divided into the aggravation and remission groups based on disease progression within one week of admission. Results: Cross-sectional comparison showed that endoplasmic reticulum molecular chaperone-binding immunoglobulin protein (ERC-BiP), angiotensinogen (AGT), ceramide acid (Cer), and C-reactive protein (CRP) levels were significantly increased in COVID-19 patients, while the sphingomyelin (SM) level was significantly decreased (P < 0.05). In addition, longitudinal comparative analysis found that the temporal fold changes of ERC-BiP, AGT, Cer, CRP, and SM were significantly different between the patients in the aggravation and remission groups (P < 0.05). ERC-BiP, AGT, and Cer levels were significantly increased in aggravation patients, while SM was significantly decreased (P < 0.05). Meanwhile, ERC-BiP was significantly correlated with AGT (r = 0.439; P < 0.001). Conclusions: ERC-BiP can be used as a core index to reflect the degree of ER stress in COVID-19 patients, which is of great value for evaluating the functional state of cells. A functional pathway for AGT/ERC-BiP/glycolysis can directly assess the activation of unfolded protein reactions. The ERC-BiP pathway is closer to the intracellular replication pathway of SARS-CoV-2 and may help in the development of predictive protocols for COVID-19 exacerbation.

Immunoassay and mass cytometry revealed immunological profiles induced by inactivated BBIBP COVID-19 vaccine.

With the global prevalence of COVID-19 and the constant emergence of viral variants, boosters for COVID-19 vaccines to enhance antibody titers in human bodies will become an inevitable trend. However, there is a lack of data on antibody levels and the protective effects of booster injections. This study monitored and analyzed the antibody potency and the antibody responses induced by the booster injection in the subjects who received three vaccine doses. The study was conducted in a multicenter collaboration and recruited 360 healthy adults aged 20-74. Participants received the first, second, and booster doses of inactivated Sinopharm/BBIBP COVID-19 vaccine at 0, 1, and 7 months. Vaccine-induced virus-specific antibody levels (SARS-COV-2-IgA/IgM/IgG) were monitored at multiple time points, surrogate virus neutralization test (sVNT), and the spatial distribution and proportion of immune cells and markers were analyzed using the CyTOF method before vaccination and a month after the second dose. The titers of SARS-CoV-2-IgA/IgM/IgG and neutralizing antibodies increased to a high level in the first month after receiving the second dose of vaccine and declined slowly after that. The antibody levels of SARS-CoV-2-IgG and sVNT were significantly increased at 0.5 months after the induction of the booster (p < 0.05). Despite a downward trend, the antibody levels were still high in the following 6 months. The B cell concentration (in humoral sample) a month after the second injection was significantly reduced compared to that before the vaccine injection (p < 0.05). The proportion of the C01 cell cluster was significantly decreased compared with that before vaccine injection (p < 0.05). Individual cell surface markers showed distinctions in spatial distribution but were not significantly different. This study has shown that serum antibody titer levels will decrease with time by monitoring and analyzing the antibody efficacy and the antibody reaction caused by the booster injection of healthy people who received the whole vaccination (completed three injections). Still, the significant peak of the antibody titer levels after booster highlights the recall immune response. It can maintain a high concentration of antibody levels for a long time, which signifies that the protection ability has been enhanced following the injection of booster immunization. Additionally, CyTOF data shows the active production of antibodies and the change in the immunity environment.

Humoral immune response of BBIBP COVID-19 vaccination before and after the booster immunization.

BACKGROUND: The inactivated Sinopharm/BBIBP COVID-19 vaccine has been widely used in the world and has joined the COVAX vaccine supply program for developing countries. It is also well adapted for usage in low- and middle-income nations due to their low storage requirements. OBJECTIVE: This study aims to report on the kinetics, durability, and neutralizing ability of the induced immunity of the BBIBP vaccine, and the intensified antibody response elicited by the booster. METHODS: A total of 353 healthy adult participants, aged 20-74 years, were recruited in this multicenter study. A standard dose of the BBIBP vaccine was administered (Month 0), followed by a second standard dose (Month 1), and a booster dose (after Month 7). Vaccine-induced virus-specific antibody levels (SARS-CoV-2-IgA/IgM/IgG), conventional virus neutralization test (cVNT), pseudovirus neutralization test (pVNT), and surrogate virus neutralization test (sVNT) were monitored over multiple time points. RESULTS: Neutralizing titers induced by the two doses of inactivated vaccine for COVID-19 peaked at Month 2 and declined to 33.89% at Month 6. Following the booster dose, elevated levels of antibodies were induced for IgA, IgG, and neutralizing antibodies, with neutralizing titer reaching 13.2 times that of before the booster. CONCLUSION: By monitoring the antibody titer levels postvaccination, this study has shown that serum antibody levels will decrease over time, but a notable spike in antibody levels postbooster highlights the anamnestic immune response. This signifies that the protection capability has increased following the injection of booster immunization.

Clinical relevance of serum Krebs von den Lungen-6 levels in patients with coronavirus disease 2019.

The clinical relevance of Krebs von den Lungen-6 (KL-6) levels in patients with coronavirus disease 2019 (COVID-19) is unclear. This study aimed to evaluate the correlation between KL-6 levels, laboratory parameters, and clinical outcomes. We enrolled 364 patients with confirmed COVID-19 who were hospitalized within 1 week of symptom onset. Their serum KL-6 level was measured on admission. Demographic data, symptoms, comorbidities, and laboratory parameters were recorded at the time of admission. Days to nucleic acid conversion and days of hospitalization were defined as clinical outcomes for evaluating the clinical relevance of serum KL-6 levels in COVID-19. Patients with elevated KL-6 levels were significantly older; had more reported instances of fever, cough, fatigue, and wheezing; and a longer hospital stays than those with normal KL-6 levels; the difference was statistically significant (p < 0.001). Furthermore, KL-6 levels was associated with the days of hospitalization and various laboratory parameters that influence the severity and prognosis of COVID-19. Elevated KL-6 levels have also been shown to be an independent risk factor for prolonged hospitalization. Our data suggest that serum KL-6 levels on admission can serve as an indicator for assessing the clinical outcomes of COVID-19.

Metabolomics reveals a correlation between hydroxyeicosatetraenoic acids and allergic asthma: Evidence from three years' immunotherapy.

BACKGROUND: Subcutaneous immunotherapy (SCIT) is an effective, safe, preventative treatment for allergic asthma; however, potential biomarkers for monitoring SCIT have rarely been reported. OBJECTIVE: Metabolomics was utilized for the discovery of new biomarkers and analyzing disease pathophysiology of allergic asthma, and it was also applied to determine the metabolomic profiles of serum samples from children with asthma undergoing SCIT and identify potential biomarkers for allergic asthma and its therapeutic monitoring. METHODS: Untargeted metabolomics using ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry was performed on 15 asthmatic and 15 healthy pediatric sera to profile carboxylic acids. Statistical analysis combined with pathway enrichment analysis was applied to identify potential biomarkers. Then, targeted metabolomics was performed to study longitudinal changes of eicosanoid profiles on sera from 20 participants with asthma who received SCIT at baseline, 6 months, one, two, and three years (ChiCTR-DDT-13003728). RESULTS: Metabolomic analysis revealed that levels of eicosanoids, particularly 12(S)-hydroxyeicosatetraenoic acid (HETE; AUC = 0.94, p < .0001) and 15(S)-HETE (AUC = 0.89, p = .0028), metabolized from arachidonic acid by lipoxygenase and glutathione peroxidase enzymes, were significantly higher in asthma group than in healthy individuals. Furthermore, levels of these important metabolites increased in the first year of SCIT treatment and then decreased from years one to three, being significantly lower after three years of treatment than baseline levels. CONCLUSION: 12(S)- and 15(S)-HETEs are potential biomarkers to participate in the pathogenesis and treatment of allergic asthma. Moreover, these metabolites may be a new target for biological indicators to monitor the therapeutic effect of SCIT, particularly in the setting of allergic asthma.

The sensitization characteristics of adult Chinese patients diagnosed with chronic respiratory diseases.

BACKGROUND: The prevalence of allergen-induced chronic respiratory disease (CRD) is increasing annually. OBJECTIVE: This study aimed to analyze the sensitization characteristics of adult Chinese CRD patients. METHODS: The serum specific immunoglobulin E (sIgE) was detected via an inhalation allergy screening test. Total immunoglobulin E (tIgE) levels were measured in 85 asthma patients, 98 chronic obstructive pulmonary disease (COPD) patients, and 69 patients with other CRDs. RESULTS: The total positive rate of allergy screening among CRD patients was 36.1%. Asthma showed the highest rate (45.9%), followed by COPD (32.7%) and other CRDs (29.0%). The positive rate of inhalation allergy screening was significantly higher among office staff (68.9%) than among outdoor workers (42.8%) and farmers (25.0%, P < 0.05). In patients with COPD, atopy was a risk factor for dyspnea (Odds ratio = 1.22; P < 0.05). Optimal scaling analysis revealed a correlation between tIgE levels and smoking index (Cronbach's alpha = 91.1%). Up to 35.0% of GOLD III or IV patients showed low sIgE and high tIgE. CONCLUSIONS: Patients with CRD had high sensitization. Asthma patients who work indoors were more susceptible to allergies. Atopy was associated with COPD pulmonary function. It is necessary to initially screen the sensitization situation of CRD patients.

Analysis of serum polyunsaturated fatty acid metabolites in allergic bronchopulmonary aspergillosis.

BACKGROUND: The importance of lipid mediators in allergic diseases has been long recognized, whereas little is known about their role in allergic bronchopulmonary aspergillosis (ABPA). We investigated whether lipid mediators are associated with ABPA. METHODS: We recruited 12 ABPA patients, 23 asthma patients and 12 healthy control in our study. Serum of 11 ABPA patients were collected before and following treatment. 36 polyunsaturated fatty acid metabolites were measured in serum samples by using liquid chromatography-mass spectrometry. This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University, with ethics number GYFYY-2016-73. RESULTS: Levels of arachidonic acid (AA), 15(S)-hydroxyeicosatetraenoic acid (HETE), 12(S)-HETE, 8(S)-HETE, 5(S)-HETE, LTB4, PGB2, 12(S)-hydroxyeicosapentaenoic acid (HEPE), 12-hydro-xyheptadecatrienoic acid (HHTrE) were significantly higher in ABPA patients than that in HC groups. Compared with asthma group, ABPA group expressed lower levels of 15(S)-hy-droperoxyeicosatetraenoic acid (HPETE), 5(S)-HPETE, 13(S)-hydroperoxyoctadecadienoic acid (HPODE) and 9(S)-HPODE. In APBA patients, AA level was positively correlated with serumtotal IgE (tIgE). The levels of 12(S)-HPETE, 15(S)-HEPE and 12(S)-HEPE correlated with Asp-ergillus fumigatus specific IgE(A. fumigatus sIgE) positively. Peripheral blood eosinophilia correlated with high levels of 12(S)-HETE and 15(S)-HETE. In addition, the serum levels of15(S)-HETE and 12(S)-HETE in ABPA subjects both declined with the decrease of tIgE, A. fumigatus sIgE and sIgG concentrations after treatment. CONCLUSIONS: We present data regarding the role of polyunsaturated fatty acid metabolites in APBA for the first time. Most of the tested metabolites increased in ABPA when co-mpared with healthy controls and 15(S)-HETE and 12(S)-HETE may play a role in the pat-hogenesis of ABPA. These findings can provide new ideas for diagnosis, therapy and mon-itor of ABPA.

Sensitization to Furry Animals and Clinical Relevance of House Dust Mite-Induced Allergic Rhinitis in Guangzhou, China.

INTRODUCTION: The impact of furry animal allergens on house dust mite (HDM)-induced allergic rhinitis (AR) is unclear. OBJECTIVE: We aimed to investigate the co-sensitization and cross-sensitization of furry animal allergens and assess their clinical relevance with HDM-induced AR. METHODS: We enrolled 268 patients with HDM-induced AR who were diagnosed with skin prick tests positive for dogs and/or cats. Specific immunoglobulin E (sIgE) for dogs (e1) and cats (e2), their components (Can f 1-5 and Fel d 1-2), and other uncommon furry animal extracts were measured. Symptoms and quality of life were assessed with a visual analog scale (VAS). RESULTS: The VAS scores for the AR and asthma (AS; n = 166), moderate-to-severe persistent-AR (n = 132), and e1P (positive)-e2P (n = 89) groups were higher than those for single AR (n = 102), other AR classifications, and other AR sensitization profiles, respectively. The IgE positivity rates for components such as Can f 1-3 and Fel d 2 and those for rats, sheep, mice, cows, and horses were highest in e1P-e2P patients. Can f 1-4, Fel d 1, Fel d 2, or the combined allergens were positively correlated with VAS scores. AR combined with AS and sensitization to Can f 4, Fel d 1, or mice were risk factors for HDM-induced AR with VAS scores ≥5. CONCLUSIONS: Extensive cross-sensitization or co-sensitization was found between Can f 1-3, Fel d 2, or rat, sheep, mouse, cow, and horse extracts. Higher sIgE levels for Can f 1-4 and Fel d 1-2 or a higher number of furry animal allergens lead to more severe symptoms and a reduced quality of life. Combined with AS, sensitization to Can f 4, Fel d 1, or mice were risk factors for moderate-to-severe HDM-induced AR.

Serum SP-A and KL-6 levels can predict the improvement and deterioration of patients with interstitial pneumonia with autoimmune features.

BACKGROUND: Some patients with interstitial pneumonia with autoimmune features (IPAF) showed a progressive course despite therapy. This study aimed to evaluate whether serial changes in the serum levels of surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) can predict disease progression. METHODS: Sixty-four patients with IPAF and 41 patients with non-fibrotic lung disease (non-FLD) were examined. Based on long-term changes in lung function, 36 IPAF patients who were followed up for more than 3 months were divided into a progressive group (n = 9), an improvement group (n = 13), and a stable group (n = 14). Serum KL-6 and SP-A levels were measured. The sensitivity, specificity, cut-off value, and area under the curve (AUC) value for each of the indices were determined using receiver operating characteristic (ROC) curve analysis. The expression differences in these biomarkers and their correlation with disease severity were analyzed. RESULTS: Compared with non-FLD patients, serum SP-A and KL-6 levels in IPAF patients were increased significantly [SP-A: (p < 0.001); KL-6: (p < 0.001)] and negatively correlated with DLCO (SP-A: rS = - 0.323, p = 0.018; KL-6: rS = - 0.348, p = 0.0011). In patients with progressive disease, the posttreatment serum SP-A and KL-6 levels were increased significantly compared with pretreatment levels [SP-A: (p = 0.021); KL-6: (p = 0.008)]. In patients showing improvement, the levels were decreased significantly [SP-A (p = 0.007) and KL-6 (p = 0.002)]. Changes in serum biomarkers (Delta SP-A and Delta KL-6) were significantly negatively correlated with changes in lung function (Delta FVC, Delta DLCO and Delta FEV1) (rS = 0.482, p < 0.05). A significant positive correlation was found between Delta SP-A and Delta KL-6 (rS = 0.482, p < 0.001). CONCLUSIONS: Serum SP-A and KL-6 offer high sensitivity and specificity for the diagnosis of IPAF. The decrease in serum SP-A and/or KL-6 levels in patients with IPAF is related to the improvement in pulmonary function. SP-A and KL-6 may be important biomarkers for predicting disease progression in patients with IPAF.

Distribution characteristics of cow's milk-sIgE components in children with respiratory allergic diseases in southern China.

BACKGROUND: Cow's milk (CM) is the main food allergen for toddlers and infants. Presently, studies on CM specific immunoglobulin E (sIgE) sensitization and positive distribution of CM components ALA-, CAS-, and BLG-sIgE are lacking in infants with respiratory allergic diseases, especially in southern China. This study therefore aimed to investigate the distribution of CM sensitization and the relation between its components α-lactalbumin (ALA), ß-lactoglobulin (BLG) and casein (CAS) sIgE in children with respiratory allergic diseases in southern China. METHODS: A total of 1839 children (≤12 years) with respiratory diseases and detected CM-sIgE levels were included. Serum samples were collected from the Respiratory Diseases Bioresources Center of the National Center for Respiratory Diseases in southern China from August 2012 to July 2017. ALA-, BLG-, and CAS-sIgE were detected and questionnaires were completed in 103 children. RESULTS: A total of 36.7% children were positive for CM-sIgE. CM-sIgE levels were higher in asthmatic bronchitis (AB) group than in other allergic respiratory disease groups (all P < 0.05). Among the 103 CM-sIgE-sensitized children, 64.08% had a history of family allergies. There were 84.47% of the children who tested positive for two or more sIgE components. The average ALA-, BLG-, and CAS-sIgE levels were 1.91 kU/L, 1.81 kU/L, and 0.62 kU/L, respectively. The CM-sIgE level showed a correlation with BLG-sIgE (rs = 0.833), ALA-sIgE (rs = 0.816), and CAS-sIgE (rs = 0.573) levels (all p < 0.001). CONCLUSIONS: In southern China, CM-sIgE levels were higher in children with AB than in those with other respiratory allergic diseases. ALA and BLG were the main allergenic components detected in CM-sIgE-sensitized children with respiratory allergic diseases.

Molecular allergen sensitization of Aspergillus fumigatus between allergic bronchopulmonary aspergillosis and A fumigatus-sensitized asthma in Guangzhou, Southern China.

BACKGROUND: Few studies have assessed the sensitization of mycotic allergens and Aspergillus fumigatus molecular allergens. This study aimed to investigate the relationships of A fumigatus components and mycotic allergens in allergic bronchopulmonary aspergillosis (ABPA) patients and A fumigatus (Af)-sensitized asthma patients. METHODS: Serum sIgE levels of Penicillium chrysogenum, Cladosporium herbarum, Mucor racemosus, Candida albicans, Alternaria alternata, Helminthosporium halodes, and A fumigatus allergen components (Asp f 1, Asp f 2, Asp f 3, Asp f 4, and Asp f 6) were measured via the ImmunoCAP assay in 18 ABPA and 54 Af-sensitized asthma patients in Guangzhou city, China. RESULTS: 94.44% of ABPA patients and 87.04% of Af-sensitized asthma patients were co-sensitized to at least one other fungal allergen. The positive rates of Asp f 1 (88.89% vs 59.26%, P < .05), Asp f 2 (66.67% vs 33.33%, P < .05), Asp f 4 (61.11% vs 33.33%, P < .05), and Asp f 6 (66.67% vs 14.81%, P < .001) in ABPA patients were higher than those in Af-sensitized asthma patients. IgE levels of Asp f 1 (P < .05), Asp f 4 (P < .05), and Asp f 6 (P < .001) were higher in ABPA patients than in Af-sensitized asthma patients. Optimal scale analysis showed that ABPA was more relevant to Af components (Cronbach's alpha = 90.7%). CONCLUSION: The A fumigatus components and their relationships with various mycotic allergens were different in ABPA and Af-sensitized asthma patients. This finding may help local doctors in the diagnosis and immunotherapy of fungal allergies.

Elevated serum levels of periostin in patients with allergic bronchopulmonary aspergillosis.

BACKGROUND: Serum periostin levels have been reported to be an indicator of Th2 inflammation in asthmatic patients. OBJECTIVE: This study aimed to investigate serum levels of periostin in patients with allergic bronchopulmonary aspergillosis (ABPA) and to evaluate its diagnostic and monitoring value in the disease. METHODS: Patients with ABPA (n = 19) and asthma (n = 24), including severe asthma with fungal sensitisation (SAFS, n = 11) and severe asthma without fungal sensitization (SAwFS, n = 13), were enrolled. Serum levels of periostin were analysed by enzyme-linked immunosorbent assay. Serum total IgE and Aspergillus fumigatus specific IgE, IgG were measured by ImmunoCAP. Levels of cytokines (IFN-γ, IL-4, IL-5, IL-8, IL-10, IL-13 and IL-17A) were measured by Meso Scale Discovery (MSD). RESULTS: Serum levels of periostin in ABPA patients (85.55 ng/mL, [68.28-166] ng/mL) were higher than those in SAFS (50.99 ng/mL, [32.02-71.80] ng/mL; P < 0.01). Among the analysed cytokines, IL-5 levels in ABPA (1.55 pg/mL, [0.96-3.33] pg/mL) were higher than those in SAFS (0.31 pg/mL, [0.26-0.56] pg/mL; P < 0.05) or SAwFS (0.34 pg/mL, [0.21-0.56] pg/mL; P < 0.01). Serum periostin levels was positively associated with total IgE levels (r = 0.319, P < 0.05), serum IL-5 levels (r = 0.484, P < 0.01) and blood eosinophil counts (r = 0.428, P < 0.05). In ROC analysis, the clinical reference value of periostin was 68.8 ng/mL for differential diagnosis of ABPA and SAFS, with the area under the curve (AUC) of 0.81. Longitudinally, serum periostin levels did not change significantly after treatment in ABPA. CONCLUSIONS: These findings suggested that serum levels of periostin were up-regulated in ABPA patients, which may be associated with eosinophilic inflammation.

Co-sensitization and cross-reactivity of Blomia tropicalis with two Dermatophagoides species in Guangzhou, China.

BACKGROUND: Contradictory results have been reported previously in the analyses of cross-reactivity among Blomia tropicalis (Blo t), Dermatophagoides pteronyssinus (Der p), and Dermatophagoides farinae (Der f). This study aims to investigate the characteristics of co-sensitization and the IgE cross-reactivity among them and attempts to identify whether patients are sensitized to Blo t due to cross-reaction or true sensitization. METHODS: Specific IgE (sIgE) in the sera from 1497 allergenic patients was determined by ImmunoCAP. Cross-reactivity was analyzed and determined by sIgE inhibition with 21 sera samples. RESULTS: Around 85.50% of patients were sensitized to Der p, 85.37% of patients were sensitized to Der f, and 71.54% of patients were sensitized to Blo t. Further, 70.14% of patients were co-sensitized to Blo t, Der p, and Der f, and only seven patients were sensitized solely to Blo t. With increasing sIgE levels for Blo t, the positive rates of severe-level (class 5-6) co-sensitization to Der p or Der f significantly increased. Blo t was moderately associated with Der p and Der f, with correlation coefficients of 0.6998 and 0.6782, respectively. Der p and Der f inhibited IgE binding to Blo t more strongly than Blo t inhibited IgE binding to Der p or Der f in the patient groups CBlo t  < CDer p and CBlo t  < CDer f . CONCLUSIONS: This study has established valuable information about the co-sensitization and cross-reactivity of Blo t with two Dermatophagoides species (Der p and Der f) and helps to provide adequate diagnosis and treatment of the mite-allergic patients.

Comparative Analysis of Serum Allergen sIgE Detected by Western Blotting and Fluorescent Enzyme Immunoassay.

BACKGROUND: Various new methods to diagnose allergens have gradually developed in recent years. The present study aimed to evaluate the diagnostic performance and clinical utility of Allergy-Q detection system (Proteometech Inc., Korea) on serum allergen-specific IgE (sIgE). METHODS: Immunoblotting (Allergy-Q system) and fluorescent enzyme immunoassay (ImmunoCAP system, Phadia Inc., Sweden) were used to detect serum total IgE and allergen sIgE of 244 cases of allergic diseases, followed by comparative analysis of the results. The study focused on analyzing 15 kinds of common allergens. RESULTS: Comparison of the two methods showed that the diagnostic performance of qualitative results of AllergyQ system for the majority of allergens was satisfactory, with Dermatophagoides farinae having the highest agreement (96.4%) and sensitivity (97.8%) and Dermatophagoides pteronyssinus having the highest specificity (100%), positive predictive value (100%), and Youden's index (J = 0.951). Scatter plots and Spearman's correlation analysis showed correlations between the quantitative results of the two methods, with the highest correlation for Dermatophagoides pteronyssinus (r = 0.875, p < 0.001). CONCLUSIONS: For most common allergens, the Allergy-Q system is an effective method for diagnosis. It is safe, convenient, economical, accurate, and efficient in screening multi-allergens. Moreover, it is good for semi-quantitative detection of allergens in the basic hospitals that are unable to carry out the ImmunoCAP detection, and also for patients with fewer samples. However, its clinical application needs to be validated using a number of samples from a variety of countries and regions.