Protein kinase CK2 enables regulatory T cells to suppress excessive TH2 responses in vivo.

The quality of the adaptive immune response depends on the differentiation of distinct CD4(+) helper T cell subsets, and the magnitude of an immune response is controlled by CD4(+)Foxp3(+) regulatory T cells (Treg cells). However, how a tissue- and cell type-specific suppressor program of Treg cells is mechanistically orchestrated has remained largely unexplored. Through the use of Treg cell-specific gene targeting, we found that the suppression of allergic immune responses in the lungs mediated by T helper type 2 (TH2) cells was dependent on the activity of the protein kinase CK2. Genetic ablation of the ß-subunit of CK2 specifically in Treg cells resulted in the proliferation of a hitherto-unexplored ILT3(+) Treg cell subpopulation that was unable to control the maturation of IRF4(+)PD-L2(+) dendritic cells required for the development of TH2 responses in vivo.

Identification of plasma protein markers of allergic disease risk: a mendelian randomization approach to proteomic analysis.

BACKGROUND: While numerous allergy-related biomarkers and targeted treatment strategies have been developed and employed, there are still signifcant limitations and challenges in the early diagnosis and targeted treatment for allegic diseases. Our study aims to identify circulating proteins causally associated with allergic disease-related traits through Mendelian randomization (MR)-based analytical framework. METHODS: Large-scale cis-MR was employed to estimate the effects of thousands of plasma proteins on five main allergic diseases. Additional analyses including MR Steiger analyzing and Bayesian colocalisation, were performed to test the robustness of the associations; These findings were further validated utilizing meta-analytical methods in the replication analysis. Both proteome- and transcriptome-wide association studies approach was applied, and then, a protein-protein interaction was conducted to examine the interplay between the identified proteins and the targets of existing medications. RESULTS: Eleven plasma proteins were identified with links to atopic asthma (AA), atopic dermatitis (AD), and allergic rhinitis (AR). Subsequently, these proteins were classified into four distinct target groups, with a focus on tier 1 and 2 targets due to their higher potential to become drug targets. MR analysis and extra validation revealed STAT6 and TNFRSF6B to be Tier 1 and IL1RL2 and IL6R to be Tier 2 proteins with the potential for AA treatment. Two Tier 1 proteins, CRAT and TNFRSF6B, and five Tier 2 proteins, ERBB3, IL6R, MMP12, ICAM1, and IL1RL2, were linked to AD, and three Tier 2 proteins, MANF, STAT6, and TNFSF8, to AR. CONCLUSION: Eleven Tier 1 and 2 protein targets that are promising drug target candidates were identified for AA, AD, and AR, which influence the development of allergic diseases and expose new diagnostic and therapeutic targets.

Plasma polyamines during pregnancy and their relationships with maternal allergies and the immune response of the neonates.

BACKGROUND: Some studies have reported that polyamine levels may influence immune system programming. The aim of this study was to evaluate the polyamine profile during gestation and its associations with maternal allergy and cytokine production in cord blood cells in response to different allergenic stimuli. METHODS: Polyamines were determined in plasma of pregnant women (24 weeks, N = 674) and in umbilical cord samples (N = 353 vein and N = 160 artery) from the Mediterranean NELA birth cohort. Immune cell populations were quantified, and the production of cytokines in response to different allergic and mitogenic stimuli was assessed in cord blood. RESULTS: Spermidine and spermine were the most prevalent polyamines in maternal, cord venous, and cord arterial plasma. Maternal allergies, especially allergic conjunctivitis, were associated with lower spermine in umbilical cord vein. Higher levels of polyamines were associated with higher lymphocyte number but lower Th2-related cells in cord venous blood. Those subjects with higher levels of circulating polyamines in cord showed lower production of inflammatory cytokines, especially IFN-α, and lower production of Th2-related cytokines, mainly IL-4 and IL-5. The effects of polyamines on Th1-related cytokines production were uncertain. CONCLUSIONS: Spermidine and spermine are the predominant polyamines in plasma of pregnant women at mid-pregnancy and also in umbilical cord. Maternal allergic diseases like allergic conjunctivitis are related to lower levels of polyamines in cord vein, which could influence the immune response of the newborn. Cord polyamine content is related to a decreased Th2 response and inflammatory cytokines production, which might be important to reduce an allergenic phenotype in the neonate.

IgE-Binding Monocytes Have an Enhanced Ability to Produce IL-8 (CXCL8) in Animals with Naturally Occurring Allergy.

IL-8 is a potent chemokine that recruits neutrophils and basophils to promote inflammation in many species. IL-8 is produced by many cell types, including monocytes. In this study, we report a novel role for IgE-binding monocytes, a rare peripheral immune cell type, to promote allergic inflammation through IL-8 production in a horse model of natural IgE-mediated allergy. We developed a mAb with confirmed specificity for both recombinant and native equine IL-8 for flow cytometric analysis. Equine IL-8 was produced by CD14+/MHC class II+/CD16- monocytes, including a subpopulation of IgE-binding monocytes, following stimulation with LPS. In addition, IgE cross-linking induced IL-8 production by both peripheral blood basophils and IgE-binding monocytes. IL-8 production was compared between healthy horses and those with a naturally occurring IgE-mediated skin allergy, Culicoides hypersensitivity. Allergic horses had significantly higher percentages of IL-8+ IgE-binding monocytes after IgE cross-linking. In contrast, frequencies of IL-8+ basophils after IgE cross-linking were similar in all horses, regardless of allergic disease, highlighting IgE-binding monocytes as a novel source of IL-8 during allergy. We concluded that IgE-binding monocytes from allergic individuals have an increased capacity for IL-8 production and likely contribute to the recruitment of innate immune cells during IgE-mediated allergy and promotion of inflammation during repeated allergen contact.

Influence of the COVID-19 pandemic on the incidence and exacerbation of childhood allergic diseases.

To explore the influence of changes in human lifestyle and the living environment caused by nonpharmaceutical interventions in coronavirus disease 2019 (COVID-19) on allergic diseases, the present study enrolled children who came to the Children's Hospital of Zhejiang University for allergen detection between January 2019 and December 2020. By comparing the positive rates and levels of various allergen-specific immunoglobulin E (IgE) before and during the COVID-19 pandemic, the influence of changes in human lifestyle and the living environment caused by prevention and control measures in COVID-19 on allergic diseases was evaluated. In 2019, 41 648 allergic children went to the hospital, but in 2020, due to the impact of the COVID-19 epidemic, the number decreased to 24 714. In 2020, the number of allergy visits was the lowest in February and gradually increased. There were 45 879 children with total IgE > 17.5 IU/ml in 2 years, accounting for 69.13% of the total samples, of which the proportion was 68.52% (28 536/41 648) in 2019 and 70.17% (17 343/24 714) in 2020. A total of 29 906 children were positive for one or more allergens in 2 years. It accounts for 45.06% of the total number of samples, of which the proportion is 41.53% (17 296/41 648) in 2019 and 51.02% (12 610/24 714) in 2020. Except for cashew nuts, the positive number of other allergens in 2020 was less than in 2019, especially after June and July 2020. Except for Artemisia argyi, the positive rates of other allergens in 2020 were significantly higher than those in 2019 (p < 0.05). Moreover, the changing trend of the positive allergen rate in each month in 2020 was different from that in 2019. In 2020, except for Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Crab, specific IgE levels of other allergens were not greater than those in 2019 (p < 0.05). Thus it can be seen, during the COVID-19 pandemic, nonpharmaceutical interventions played a protective role in reducing children's exposure to allergens and alleviating allergic reactions.

Patients with mast cell activation symptoms and elevated baseline serum tryptase level have unique bone marrow morphology.

BACKGROUND: Patients with mast cell (MC) activation symptoms and elevated baseline serum tryptase level (MCAS-T) may not necessarily have a clonal MC disorder. Many are diagnosed with hereditary α-tryptasemia (HαT), a genetic trait characterized by autosomal dominant inheritance of multiple copies of TPSAB1 encoding α-tryptase and increased risk for severe anaphylaxis. OBJECTIVE: The aim of our study was to identify and characterize bone marrow MC histopathologic features specific for MCAS-T. METHODS: A total of 43 patients with MCAS-T underwent evaluation, including bone marrow biopsy, for a MC disorder. The results of the work-up for clonal MC disorders such as systemic mastocytosis and monoclonal MC activation syndrome were negative. Bone marrow MC histopathology was reviewed to identify characteristic features of MCAS-T. A subgroup of patients was available for tryptase genotyping. RESULTS: Patients with MCAS-T showed unique morphologic and histologic features when compared with controls. MCs were larger (P < .01), hypogranular (P < .01), frequently detected in paratrabecular (P < .05) and perivascular (P < .01) locations, and associated with bone marrow eosinophilia (P < .01). A total of 10 patients who were available for tryptase genotyping were all confirmed to have HαT. This subgroup was representative of the larger MCAS-T cohort. CONCLUSION: We report unique bone marrow MC phenotypic and histopathologic changes in patients with MCAS-T. These morphologic changes are associated with an elevated tryptase level that has been confirmed to be caused by HαT in all patients available for testing.

Unboxing dendritic cells: Tales of multi-faceted biology and function.

Often referred to as the bridge between innate and adaptive immunity, dendritic cells (DCs) are professional antigen-presenting cells (APCs) that constitute a unique, yet complex cell system. Among other APCs, DCs display the unique property of inducing protective immune responses against invading microbes, or cancer cells, while safeguarding the proper homeostatic equilibrium of the immune system and maintaining self-tolerance. Unsurprisingly, DCs play a role in many diseases such as autoimmunity, allergy, infectious disease and cancer. This makes them attractive but challenging targets for therapeutics. Since their initial discovery, research and understanding of DC biology have flourished. We now recognize the presence of multiple subsets of DCs distributed across tissues. Recent studies of phenotype and gene expression at the single cell level have identified heterogeneity even within the same DC type, supporting the idea that DCs have evolved to greatly expand the flexibility of the immune system to react appropriately to a wide range of threats. This review is meant to serve as a quick and robust guide to understand the basic divisions of DC subsets and their role in the immune system. Between mice and humans, there are some differences in how these subsets are identified and function, and we will point out specific distinctions as necessary. Throughout the text, we are using both fundamental and therapeutic lens to describe overlaps and distinctions and what this could mean for future research and therapies.

Molecular analysis of phenotypic interactions of asthma.

INTRODUCTION: Asthma is a heterogeneous disease characterized by multiples respiratory symptoms; this is a polygenic entity that involves a complex interaction of environmental factors and inherent to the individual. To understand the development of asthma, some phenotypes have been proposed. OBJECTIVE: This work's purpose was to explore different molecules related to asthma development and to define each phenotype's specific characteristics. MATERIAL AND METHODS: 96 adult patients diagnosed with asthma before any treatment were enrolled in the protocol. Spirometric parameters, circulating leukocytes, serum IgE, body mass index, exhaled nitric oxide (FENO), and leukotrienes (LTB4) in urine were determined in each patient. The presence of asthma phenotypes proposed by the Global Initiative for Asthma (GINA) were explored: A) Allergic asthma, B) Non-allergic asthma, C) Late-onset asthma, D) Asthma with persistent airflow limitation, and E) Asthma with overweight and obesity. RESULTS: In the cohort analyzed, we found four of phenotypes proposed by GINA; however, these phenotypes overlapped, due to this, 4 groups were integrated with allergic, non-allergic and obese patients, which were the main phenotypes. The main overlap was that of patients not-obese allergic, and was characterized by earlier onset, elevated levels of IgE, LTB4 and inflammasome related cytokines. Non-allergic patients had a significant association between interleukin (IL)-18 and IL-18 binding protein (BP) with narrow ratio between these cytokines. Finally, LTB4 had remarkable capacity to discriminate between allergic and not allergic patients. CONCLUSIONS: Asthmatic phenotypes exist as interrelated characteristics and not as discrete entities. High levels of leukotrienes and IgE are hallmarks in the allergic phenotype of asthma.

Bee- and Wasp-Venom Sensitization in Schoolchildren of High- and Low-Socioeconomic Status Living in an Urban Area of Indonesia.

BACKGROUND: There is not much known about venom allergy in tropical regions. Here, we studied the prevalence of specific IgE (sIgE) and skin prick test (SPT) reactivity and reported sting-related symptoms, in high- and low-socioeconomic status (SES) schoolchildren living in urban city of Makassar in Indonesia. METHODS: Children from high- (n = 160) and low- (n = 165) SES schools were recruited. Standardized questionnaires were used to record information on allergic disorders as well as sting-related symptoms. Parasitic infection, SPT reactivity, and sIgE to Apis mellifera (bee-venom) as well as Vespula spp. (wasp-venom) were assessed. RESULTS: SPT reactivity to bee- and wasp-venom was 14.3 and 12.7%, while the prevalence of sIgE was 26.5 and 28.5%, respectively. When SES was considered, prevalence of SPT to bee- and wasp-venom was higher in high-SES than in low-SES schoolchildren (bee: 22.8 vs. 5.7%, p < 0.001; and wasp: 19.6 vs. 5.7%, p < 0.001). Conversely, sIgE to both venoms was lower in high-SES than in low-SES (bee: 19 vs. 34%, p = 0.016; and wasp: 19 vs. 38%, p = 0.003). Furthermore, among SPT positive subjects, considerable proportion had no detectable sIgE to bee- (65.85%) or wasp-venom (66.67%). Altogether the sensitizations were rarely translated into clinical reaction, as only 1 child reported significant local reaction after being stung. No association with parasitic infections was found. CONCLUSIONS AND CLINICAL RELEVANCE: Sensitization against bee- or wasp-venom is quite prevalent among schoolchildren in Indonesia. The discordance between SPT and sIgE might suggest the direct (non-IgE) effect of venoms in skin reactivity. Recorded sensitizations had poor clinical relevance as they rarely translated into clinical symptoms.

The peripheral blood inflammatory patterns in the control levels of asthma in children.

OBJECTIVE: Asthma is the most common chronic inflammatory disease of childhood, but there are no useful and easily accessible laboratory tests routinely used in the diagnosis and follow-up of this disease in children. Therefore, this study aimed to investigate the roles of white blood cell (WBC) count, platelet count, mean platelet volume (MPV), and eosinophil percentage as full blood count inflammatory markers in evaluating the control level and follow-up of asthma in the pediatric age group. METHODS: A retrospective review of patient records and files of 3,580 patients diagnosed with asthma at the University of Health Sciences in Ankara, Turkey was performed. Patients who met inclusion/exclusion criteria were divided into two groups based on the asthma control level: controlled and uncontrolled. Laboratory data were compared according to the asthma control levels, drug use status, and atopy status of the patients. RESULTS: A total of 348 patients between 4 and 18 years of age, who were followed-up with the diagnosis of asthma, were included in this study. A significant difference was found between the controlled and uncontrolled groups of asthma patients in terms of the eosinophil percentage (mean ± SD, respectively; 3.493 ± 2.24; 4.992 ± 3.43; p = .003). When patients were grouped according to their asthma control levels and atopy status, only the eosinophil percentages were different in the logistic regression analysis (odds ratio = 1.276, 95% confidence interval = 1.113-1.462). CONCLUSION: Our study showed that the percentage of eosinophils can be used as an asthma control parameter, but additional prospective studies would be desirable to confirm our results.

Serum IgE Predicts Difference of Population and Allergens in Allergic Diseases: Data from Weifang City, China.

BACKGROUND: Immunoglobulin E (IgE) is the most important promoter of allergic inflammation. However, there are few systematic studies on IgE in age range, genders, disease spectrum, and time regularity. AIM: To screen the common allergens, allergen spectrum, and IgE difference between type 2 inflammatory allergic diseases and other allergic diseases in Weifang, China. METHODS: A retrospective study was performed by estimating patients' clinical data suffering from allergic diseases (urticaria, pollinosis, allergic rhinitis, atopic dermatitis, and bronchial asthma) between May 2019 and April 2020 using an allergen detection kit of Macro-Union Pharmaceutical. RESULTS: 732 of the 1367 patients showed different antigen positive, and the positive rate was 53.5%. The most common allergens were dust mites, mixed fungi, Artemisia pollen, cat/dog dander, and cockroaches. There were 27.0% (369/1367) of the patients with single positive allergen-specific IgE (sIgE), 26.5% (363/1367) with multiple-positive IgE. The total immunoglobulin E (tIgE) levels varied with gender, age, and type of disease. There was a difference in the distribution of allergens between children and adults. A positive correlation between the serum-specific IgE and the corresponding local inhaled allergen density was observed. CONCLUSIONS: In this study, we found that type 2 inflammatory allergic diseases have higher serum IgE and a higher probability of inhaled sIgE positive. According to age, gender, and condition, serological IgE detection of allergens provides new insight into the early diagnosis and prevention of allergic diseases.

Titanium Dioxide Nanoparticles Exacerbate Allergic Airway Inflammation via TXNIP Upregulation in a Mouse Model of Asthma.

Titanium dioxide nanoparticles (TiO2NPs) are widely used in industrial and medicinal fields and in various consumer products, and their increasing use has led to an increase in the number of toxicity studies; however, studies investigating the underlying toxicity mechanism have been rare. In this study, we evaluated potential toxic effects of TiO2NPs exposure on lungs as well as the development of asthma through the ovalbumin (OVA)-induced mouse model of asthma. Furthermore, we also investigated the associated toxic mechanism. TiO2NPs caused pulmonary toxicity by exacerbating the inflammatory response, indicated by an increase in the number and level of inflammatory cells and mediators, respectively. OVA-induced asthma exposed mice to TiO2NPs led to significant increases in inflammatory mediators, cytokines, and airway hyperresponsiveness compared with those in non-exposed asthmatic mice. This was also accompanied by increased inflammatory cell infiltration and mucus production in the lung tissues. Additionally, TiO2NPs decreased the expression of B-cell lymphoma 2 (Bcl2) and the expressions of thioredoxin-interacting protein (TXNIP), phospho-apoptosis signal-regulating kinase 1, Bcl2-associated X, and cleaved-caspase 3 were escalated in the lungs of asthmatic mice compared with those in non-exposed asthmatic mice. These responses were consistent with in vitro results obtained using human airway epithelial cells. TiO2NPs treated cells exhibited an increase in the mRNA and protein expression of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α with an elevation of TXNIP signaling compared to non-treated cells. Moreover, pathophysiological changes induced by TiO2NP treatment were significantly decreased by TXNIP knockdown in airway epithelial cells. Overall, TiO2NP exposure induced toxicological changes in the respiratory tract and exacerbated the development of asthma via activation of the TXNIP-apoptosis pathway. These results provide insights into the underlying mechanism of TiO2NP-mediated respiratory toxicity.

Childhood allergy is preceded by an absence of gut lactobacilli species and higher levels of atopy-related plasma chemokines.

Alterations in the composition and reduced diversity of the infant microbiome are associated with allergic disease in children. Further, an altered microbiota is linked to immune dysregulation, including skewing of different T helper (Th) subsets, which is also seen in atopic individuals. The aim of this study was, therefore, to investigate the associations between gut lactobacilli and Th-related plasma factors in allergy development during childhood. A total of 194 children with known allergy status at 1 year of age were followed to 10 years of age. We used real-time polymerase chain reaction (PCR) to investigate the presence of three lactobacilli species (Lactobacillus casei, L. paracasei, L. rhamnosus) in infant fecal samples (collected between 1 week and 2 months of age) from a subgroup of children. Plasma chemokines and cytokines were quantified at 6 months and at 1, 2, 5 and 10 years of age with Luminex or enzyme-linked immunosorbent assay (ELISA). Fractional exhaled nitrogen oxide (FeNO) was measured and spirometry performed at 10 years of age. The data were analysed by non-parametric testing and a logistic regression model adjusted for parental allergy. An absence of these lactobacilli and higher levels of the chemokines BCA-1/CXCL13, CCL17/TARC, MIP-3α/CCL20 and MDC/CCL22 in plasma at 6 months of age preceded allergy development. The presence of lactobacilli associated with lower levels of atopy-related chemokines during infancy, together with higher levels of interferon (IFN)-γ and lower FeNO during later childhood. The results indicate that the presence of certain lactobacilli species in the infant gut may influence allergy-related parameters in the peripheral immune system, and thereby contribute to allergy protection.

Circulating microRNAs correlate to clinical parameters in individuals with allergic and non-allergic asthma.

BACKGROUND: Asthma is a chronic airway disease affecting millions of people. Better methods to define asthma subgroups using clinical parameters and molecular biomarkers are crucial in the development of personalized medicine. OBJECTIVE: The aim of this study was to determine if circulating microRNAs (miRNAs) may be used to distinguish well-defined asthma groups. METHODS: Blood serum from 116 well-defined subjects, including healthy controls and individuals with allergic or non-allergic asthma, from the West Sweden Asthma Study were included. Serum was analyzed for circulating miRNA expression of miR-126, - 145, -146a, - 155, - 223, and -374a and eosinophil cationic protein (ECP). Correlations between clinical characteristics and circulating miRNA expression as well as potential miRNA gene targets were investigated. RESULTS: A subset of miRNAs were differentially expressed between allergic and non-allergic asthmatic individuals. Alterations in expression of miR-155, -146a, -374a and - 145 were observed in allergic asthmatics in response to inhaled corticosteroid usage. Additionally, miR-223 and miR-374a expression varied in non-allergic asthmatics based on blood eosinophil numbers. Numerous clinical parameters, including lung function measurements, correlated with subsets of miRNAs. Finally, pathway analysis revealed a potential role for inhaled corticosteroid induced miRNAs in leukocyte regulation, IL-6 signaling and glucocorticoid response. CONCLUSION: Circulating miRNA expression was altered in subjects with allergic and non-allergic asthma and correlated to clinical parameters including lung function and potential gene targets involved in immune processes. This combination of clinical and molecular data may be a basis for the further, more precise classification of asthma subgroups. Taken together, these findings would further asthma research and benefit future patients through the discovery of molecular mechanisms as well as identifying asthma subgroups contributing to the development of personalized medicine.

Profilin is a marker of severity in allergic respiratory diseases.

BACKGROUND: The capacity of profilin to induce allergic symptoms in patients with respiratory allergy has been questioned. In this sense, the aim of this study was to investigate the correlation between profilin exposure and induction of symptoms in a prospective case-control study. METHODS: The concentration of profilin as well as pollen levels in the air was measured. A diary score of symptoms was collected from allergic patients. Seventy-nine individuals were included in the study; fifty cases and 28 controls were positive or negative to profilin, respectively. Conjunctival and bronchial provocation tests were performed with purified profilin (Pho d 2) in a subgroup of cases and controls. RESULTS: Profilin was detected in the environment on 133 days (maximum peak of 0.56 ng/m3 ). A positive correlation between profilin and pollen count of Olea and Poaceae was observed (ρ = 0.24; P < .001). Intensity of total, nasal and ocular symptoms was statistically higher in cases than in controls (P < .001). The risk of suffering symptoms, measured by the percentage of patients who presented any of the symptoms each day, was also higher in cases than in controls. The provocation test was positive in 95% of bronchial and 90% of conjunctival challenges in cases, and negative in all controls. CONCLUSIONS: Profilin was detected in the environment and had the ability to induce a specific allergen response. Patients sensitized to this panallergen showed more symptoms and were more likely to have symptoms. Therefore, sensitization to profilin seems to be a marker of severity in patients with rhinoconjunctivitis and asthma mediated by pollen.

Successful prevention of severe allergic transfusion reactions with omalizumab.

BACKGROUND: Allergic transfusion reactions (ATRs) are a common adverse reaction to transfusion therapy and can be potentially fatal. Washing blood products is the most effective strategy for preventing ATRs; however, washed products, especially platelets, are not available at many blood centers. STUDY DESIGN AND METHODS: A 29-year-old female patient with an advanced myelodysplastic/myeloproliferative neoplasm, unclassifiable, developed severe ATRs after four platelet transfusions in a week. She showed no response to premedication with histamines and steroids and still had severe ATRs with the next three platelet transfusions. A laboratory workup revealed that her IgA level was slightly decreased, while her haptoglobin level was normal. Anti-IgA testing was not available. The patient decided to undergo allogeneic peripheral blood stem cell (PBSC) transplantation. As the onset of symptoms ATR, which were similar to Type 1 hypersensitivity reactions mediated by IgE antibodies, occurred immediately after transfusion and omalizumab is a humanized monoclonal anti-IgE, we elected to offer off-label use of omalizumab before administering the conditioning regimen. RESULTS: Omalizumab was injected subcutaneously at a dose of 150 mg. Surprisingly, transfusion reactions fully resolved within 24 hours. No serious side effects were noticed. Another 150 mg of omalizumab was administered 1 day before PBSC infusion. The patient remained asymptomatic without any signs of ATRs throughout the whole period of transplantation. Seven months after transplantation, the patient was in complete remission without overt complications. CONCLUSION: This case suggests that omalizumab is a promising new alternative treatment for the prevention of severe ATRs.

Validation of the analytical performance of the NOVEOS™ System, a system which improves upon the third-generation in vitro allergy testing technology.

Objectives Detection of allergen-specific immunoglobulin E (sIgE) is important for the diagnosis of allergy. IgE sensitization is commonly demonstrated in vivo by skin prick testing (SPT), or in vitro utilizing automated systems. Recently, HYCOR® Biomedical launched its new system for allergen sIgE testing called the NOVEOS™ Immunoanalyzer. This study aims to evaluate the analytical performance of the NOVEOS system in a bi-center study at Philipps-University Marburg (Site-1) and Charité Medical University Berlin (Site-2), respectively. Methods The analytical performance was evaluated based on the guidelines I/LA20-A3, EP5-A3, EP17-A2, EP6-A, EP7-A3, and EP9-A3 of the Clinical and Laboratory Standards Institute (CLSI). Results The conducted repeatability and within-laboratory precision tests provided acceptable performance with 3.0%-11.9% coefficient of variation across both sites. The limit of blank (LoB) and limit of detection (LoD) were <0.1 kU/L at both centers. A within-parameter linearity for all tested allergens was reported at both sites. Of note, no significant interference was observed for high levels of biotin, methylprednisolone, diphenhydramine, omalizumab, or ranitidine. Method comparison between the NOVEOS calibration and the latest World Health Organization (WHO) reference standard showed good agreement at both sites. Conclusions The results from the analytical performance of the NOVEOS allergen sIgE assay and instrument testing at both sites were comparable. Overall, a good precision and linearity as well as a detection limit <0.1 kU/L were observed, with minimal impact of common interfering substances on patient recoveries. The NOVEOS is calibrated to the latest WHO reference standard and adds benefits like a small sample size and para-magnetic microparticles that improve upon third-generation allergen sIgE assays' design and performance.

Promoter Genotyping and mRNA Expression - Based Analysis of the PTGDR Gene in Allergy.

BACKGROUND AND OBJECTIVE: Prostaglandin D2 receptors are acquiring a relevant role as potential therapeutic targets in allergy. PTGDR has been described as a candidate gene in allergic disease, although functional studies on this gene are lacking. Objective: The objective of this case-control study was to investigate the potential role of PTGDR in allergy. METHODS: The study population comprised 195 allergic patients and 112 healthy controls. The PTGDR promoter polymorphisms -1289G>A, -1122T>C, -881C>T, -834C>T, -613C>T, -549T>C, -441C>T, -197T>C, and -95G>T were amplified by polymerase chain reaction (PCR) and sequenced. PTGDR expression levels were analyzed using quantitative PCR and normalized to GAPDH and TBP mRNA levels. All procedures were performed following the Minimum Information for Publication of Quantitative Real-Time PCR Experiment guidelines. RESULTS: PTGDR expression levels were significantly higher in allergic patients than in controls (P<.001). Receiver operating characteristic analysis for expression of PTGDR showed a sensitivity of 81.4% compared with 67% for IgE levels. In addition, differences in the genotypic distribution of the polymorphisms -1289G>A and -1122T>C were found in allergic patients (P=.009). CONCLUSIONS: The results indicate that PTGDR overexpression is associated with allergy. The polymorphisms -1289G>A and -1122T>C partly explain the variation in expression we observed. PTGDR expression could have a potential role as a biomarker and pharmacogenetic factor in allergy.

IL-33 is associated with allergy in children sensitized to the cat.

BACKGROUND: Several studies suggest that early-life exposure to animal allergens constitutes a relevant risk factor for the development of allergic sensitization. OBJECTIVES: The aim of the present study was to determine the role of interleukin-33 in children sensitive to cat allergen with allergic rhinitis and/or asthma. METHODS: The study included 51 children aged 5-18 years, both sexes, allergic to cats. Sensitization to cat allergen was confirmed by skin prick tests or specific IgE. Children were evaluated for the presence of bronchial asthma, atopic dermatitis, allergic rhinitis. A questionnaire evaluating the occurrence of allergic symptoms in children after contact with the cat and dog was performed. Mothers completed a questionnaire regarding cat exposure: during pregnancy and having a cat at home. A blood sample was taken from all children to measure the level of IL-33 in the serum. RESULTS: Keeping a cat in the home, once in the past, or having a cat in the home during the mother's pregnancy, revealed a statistically significant relationship with IL-33 levels in the studied patients. Also, daily contact with a cat during pregnancy affected the level of IL-33. Higher levels of IL-33 were shown in people with hypersensitivity to cat and pollen allergens and cat and other animals. In patients with bronchial asthma higher levels of IL-33 were found than in patients without bronchial asthma. CONCLUSIONS: Increased serum levels of IL-33 is related with keeping cats during pregnancy and in early childhood and can be associated with the development of asthma in children.

Associations between serum 25-hydroxyvitamin D levels and allergic sensitization in early childhood.

BACKGROUND AND OBJECTIVES: Vitamin D status may be related to allergen sensitizations, but the evidence is inconsistent. The objective of this study was to assess whether serum 25-hydroxyvitamin D (25(OH)D) levels were associated with allergic sensitizations in early childhood. METHODS: Data were collected from 2642 children who visited the Guangdong Women and Children's Hospital from January 2016 to May 2017 for routine health check-ups. Serum 25(OH)D levels were tested by electrochemiluminescence immunoassay. Allergic sensitizations including food and inhalant allergens were tested for specific IgE antibodies at one year (12 months 0 days through 12 months 30 days) and two years (24 months 0 days through 24 months 30 days) of age. RESULTS: The mean level of serum 25(OH)D was 86.47±27.55nmol/L, with a high prevalence of vitamin D insufficiency (<75nmol/L) in children aged 0-2 years (36.8%). Lower 25(OH)D levels with serum total IgE of more than 200IU/mL (81.54±25.53nmol/L) compared with less than 100IU/mL (87.92±28.05nmol/L). The common sensitization to allergens in children aged one and two years were milk (44.2%), cat epithelium (26.4%), egg (13.1%), dog epithelium (12.7%) and Dermatophagoides farinae (6.7%). After multivariate adjustment, data in 25(OH)D treated as a continuous variable or categories, no consistent associations were found between 25(OH)D levels and allergen-specific IgEs. CONCLUSIONS: Serum 25(OH)D level showed an inverse relationship with total IgE level in early childhood. However, there is lack of evidence to support associations between low 25(OH)D levels and allergic sensitization to various allergens.