sIgE Levels Research Articles

Longitudinal Follow-up Reveals Peripheral Immunological Changes Upon Tick Bite in a-Gal-Sensitized Individuals.

α-Gal syndrome is characterized by specific IgE (sIgE) antibodies to the carbohydrate galactose-α-1,3-galactose (α-Gal) and delayed onset of allergic symptoms after ingestion of mammalian meat. While tick bites are assumed to mediate sensitization, the immune response to tick bites has not yet been investigated. To investigate the peripheral immune response to tick bites in humans over time. In a longitudinal cohort study, immunological reactions associated with tick bites (Ixodes species) were analyzed within 1 day (V1), 2 weeks (V2), 1 month (V3), and 3 months (V4) after the occurrence of a bite. sIgE, sIgG, and sIgG subclass levels, as well as 10 cytokines, were quantified. Deep immune phenotyping was performed using mass cytometry. A total of 4 controls and 10 patients were bitten by a tick and followed up over 3 months. None of the controls developed sIgE to α-Gal, and sIgE increased in all patients from V1 until V2/V3, as did IL-8 levels. We noted a significant increase in CD19+ B cells and B-cell subpopulations, as well as a decrease in γδ CD56+ T cells in patients between V0 and V1. At V1, frequencies of plasmacytoid dendritic cells (pDCs) and γδ CD56+ T cells were lower in patients than in controls. Our study provides evidence of significant changes in several immune cell populations in α-Gal sensitized patients, along with increased levels of IL-8 and sIgE. This is the first exploratory study to investigate longitudinal peripheral immune profiles in patients and controls bitten by ticks.

Study on the Effect of Acupuncture Point Embedding on the Behavior of Rats with Allergic Rhinitis and its Mechanism of Action

To observe the interventional effect of Yingxiang acupoint embedding on the behavior of rats with allergic rhinitis and the effect on the levels of serum inflammatory factors IgE, sIgE, IL-4, and IL-5.

A Multi-centre Analysis of Serum IgE Levels in Atopic Dermatitis

Abstract Objective: To assess the characteristics of total immunoglobulin E (IgE) and allergen-specific IgE (sIgE) to 20 common allergens in 154 patients with atopic dermatitis (AD). To assess the correlation of clinical food allergy with positive food allergens’ sIgE results. We further discuss the significance of IgE as a potential biomarker for AD disease severity. Methods: A total of 154 AD patients were collected from 15 hospitals nationwide in China from 2019 to 2021. Serum IgE was measured using reverse-enzyme immuno capture test (REAST). Patients were required to have at least one positive sIgE (N ≥ 0.35 IU/mL). Patients were divided into groups according to gender, age, disease severity, and region. SPSS 26.0 software was used for statistical analysis. Results: Compared with adolescent and adult, AD in infancy and childhood showed significantly higher frequencies of positive sIgE to food allergens, including egg, cow milk, and wheat (P < 0.01). However, adolescent and adult AD showed significantly higher frequencies of positive sIgE to inhaled allergens, dermatophagoides farinae, and house dust mite. In addition, sIgE in different sexes were different. Compared with women, men showed higher frequencies of positive allergen-specific IgE level to wheat, dermatophagoides farinae, and house dust mite. The most common food allergens with elevated sIgE levels were egg (71%), cow milk (39%) and wheat (32%). However, AD patients reported seafood, including crab, shrimp, and fish, as the most frequent food allergens which aggravate their disease in their daily life. Only 18 (12%) patients reported definite correlation of clinical practice with positive food allergens’ IgE results. Among 154 sIgE-positive patients, 99 patients had an increase of total IgE (≥60 IU/ml). TotalIgE (tIgE) levels were significantly different between mild (193 ± 239 IU/mL), moderate (170 ± 202 IU/mL), and severe (375 ± 343 IU/mL) forms of AD patients (P < 0.01). AD patients with accompanied allergic diseases showed significantly higher tIgE levels than those without accompanied allergic symptoms (280 ± 286 IU/mL vs 194 ± 248 IU/mL). Conclusion: Neither sIgE nor tIgE levels can be used to evaluate the condition or severity of AD. AD patients with accompanied allergic diseases showed significantly higher tIgE levels than those without accompanied allergic symptoms. Infantile AD patients are more allergic to food, while adolescents and adults are more allergic to environmental antigens. IgE tests must be interpreted by combining with clinical history to avoid unnecessary food avoidance. Early food allergen introduction for infants may be promising for the prevention of food allergies.

Egg White Diet Induces Severe Allergic Enteritis in an Animal Model Driven by Caspase-3 and Gasdermin C-Mediated Mucosal Alarmin Secretion.

Allergic enteritis is an important phenotype of food allergies. However, there is not a suitable animal model for deeply exploring the natural progression and mechanism of allergic enteritis. In our study, we successfully developed an allergic enteritis animal model by feeding mice with an egg white diet. Following the dietary challenge, allergic mice displayed typical food allergy manifestations, including decreased core temperature, aversion to the allergenic diet, and elevated levels of serum sIgE and mMCP-1. Notably, these dietary challenged mice exhibited severe gut damage, characterized by disrupted intestinal microstructure, tissue inflammation, and edema that were evident morphologically. Moreover, upon exposure to food allergens, we observed a marked increase in caspase-3 and GSDMC levels in allergic mice. These two active proteins were found to be colocalized in damaged mucosal enterocytes and were associated with the secretion of epithelial sourced alarmins, such as IL25 and TSLP. Further data on the cellular and molecular levels suggest that such severe food-induced enteritis is mediated by the caspase-3-GSDMC pathway. We believe that this established animal model provides a valuable tool for advancing research on the mechanisms of food allergies.

Effect of mite-specific subcutaneous immunotherapy on patients with allergic rhinitis

This study analyzed the effect of mite-specific subcutaneous immunotherapy (SCIT) on patients with allergic rhinitis (AR). We enrolled 98 AR patients visiting our hospital from April 2017 to April 2019 and grouped them in a random number table. The control group (n=49) received conventional treatment for three years. The SCIT used a standardized mite allergen injection for the experimental group (n=49) for three years. The study compared total nasal symptom score (TNSS), daily medication score (DMS), total combined score (TCS), visual analog scale (VAS) score, mini-rhinitis quality of life questionnaire (MiniRQLQ) score, and serum immunoglobulin E (sIgE) level before and after treatment. The overall response rate was higher in the experimental group than in the control group (59.18% vs. 30.61%, p<0.05). After treatment, the experimental group had lower values for TCS and VAS score (p<0.05); motion score; practical problems; nasal, ocular, and other symptoms (p<0.05); and sIgE, Dermatophagoides pteronyssinus (Dp)-sIgE, and Dermatophagoides farinae (Df)-sIgE levels (p<0.05) than the control group. The sIgE, Dp-sIgE, and Df-sIgE levels were lower in the effective group than in the ineffective group (p<0.05). The areas under the ROC curves of IgE, Dp-sIgE, and Df-sIgE and their combination for predicting the therapeutic effect of mite-specific SCIT on AR were 0.839, 0.779, 0.814, and 0.903, respectively. Mite-specific SCIT relieved clinical symptoms and improved the quality of life of AR patients, probably by decreasing the IgE expression level.

Association of Mite Molecular Sensitization Profiles with Respiratory Allergies and Asthma Control in Children from East China.

Allergic conditions, identified as a significant global health challenge, are profoundly influenced by indoor allergens, especially house dust mites (HDM). Yet the relationship between mite sensitized components and respiratory allergies and asthma control remains poorly understood. A cohort of 96 children, either with allergic rhinitis (AR) or rhinitis with asthma syndrome (ARAS), was assessed. Protein microarray technology was deployed to quantify sIgE responses to the allergenic components of Der p and Der f. The study cohort comprised 18 AR and 78 ARAS patients; with 43 mild and 53 moderate-to-severe AR; with 28 uncontrolled, 21 partially controlled, and 29 well-controlled asthma. Sensitization prevalence for HDM components was highest with Der p (97.9%), Der f 2 (97.9%), Der p 2 (94.8%), Der f 1(94.8%), Der p 1 (93.8%), Der p 23 (57.3%). Notably, sIgE concentrations for Der f and Der f 2 were significantly greater in the ARAS compared to AR (P < 0.05). While sIgE levels varied between mild and moderate-to-severe AR, the differences were not statistically significant (P > 0.05). However, Der p 23 sIgE levels demonstrated a significant fluctuation across the asthma control strata (P < 0.05), with the well-controlled group exhibiting the lowest readings. The sIgE levels to HDM allergens were higher in ARAS group compared to AR group, especially Der f and Der f 2, indicating an association between sIgE reactivity and the diagnosis of asthma. Reduced Der p 23 sIgE levels were indicative of enhanced asthma control.

Recurrent tick bites induce high IgG1 antibody responses to α-Gal in sensitized and non-sensitized forestry employees in Luxembourg.

The α-Gal syndrome (AGS) is characterized by the presence of specific IgE-antibodies to the carbohydrate galactose-α-1,3-galactose (α-Gal). Sensitization to α-Gal has been associated with tick bites and individuals exposed to ticks have an elevated risk of sensitization. The aim of this study was to analyze IgG and IgE antibody responses to α-Gal in a high-risk cohort of forestry employees (FE) in Luxembourg. Questionnaires and serum samples of FE from Luxembourg (n=219) were retrospectively analyzed. α-Gal specific IgE was quantified by ImmunoCAP, α-Gal specific IgG and subclasses IgG1-4 were determined by ELISA. Additionally, sera from population-based controls (n=150) and two groups of food-allergic patients, patients with AGS (n=45) and fish-allergic patients (n=22) were assessed for IgG antibody responses to α-Gal and cod extract. Twenty-one percent of FE was sensitized to α-Gal (sIgE≥0.1kUA/L). Both sensitized and non-sensitized FE exhibited high levels of α-Gal specific IgG, IgG1 and IgG3 compared with controls, indicating a stimulation of IgG responses by recurrent tick bites, independent of the sensitization status. AGS patients had the highest levels of IgG1 and IgG2 antibodies, whereas the profile of fish-allergic patients was similar to the profile of the controls for which anti-α-Gal responses were dominated by IgG2 antibodies. α-Gal sIgG4 levels were either very low or undetectable in all groups. Our study provides evidence for a continuous stimulation of α-Gal related immune responses by repeated tick bites, translating into highly elevated levels of IgG1 antibodies directed against α-Gal.

Oral food challenge test results of patients with food allergy with specific IgE levels >100 UA/ml.

Specific IgE level (sIgE) is an important factor indicating sensitization status in children with food allergies (FAs). The present study aimed to clarify oral food challenge test (OFC) results in children with FAs with sIgE levels ≥100 UA/ml compared with those in children with sIgE <100. The retrospective study analyzed patients who underwent OFC with egg white, cow milk and wheat at Gifu Prefectural general medical center, Gifu, Japan between July 2017 and March 2023. Clinical history, total IgE (tIgE), sIgE and correlation between sIgE, sIgE/tIgE and eliciting dose as the amount of intake protein were examined. In the <100 group, positive OFC showed significantly higher sIgE for egg white, ovomucoid and casein than negative OFC (P<0.05); however, there was no significant difference between positive and negative OFC in the ≥100 group. In the <100 group, positive OFC showed significantly higher sIgE/tIgE for ovomucoid, milk and casein than negative OFC (P<0.05); however, there was no significant difference in sIgE/tIgE between positive and negative OFC in the ≥100 group. There was a significant negative correlation between eliciting dose and sIgE for egg white and wheat (P<0.05). For milk and wheat, there was no significant difference between ≥100 group and the <100 group with regard to positive rates in the OFC. Therefore, OFC may be safely performed by decreasing total challenge dose for the ≥100 group.

Clinical utility analysis of the Hoxb8 mast cell activation test for the diagnosis of peanut allergy.

Peanut allergy is among the most severe and common food allergies. The diagnosis has a significant impact on the quality of life for patients and their families. An effective management approach depends on accurate, safe, and easily implementable diagnostic methods. We previously developed a cell-based assay using Hoxb8 mast cells (Hoxb8 MCs) aimed at improving clinical allergy diagnosis. In this study, we assessed its diagnostic performance by measuring blinded sera from a prospectively enrolled and pre-validated peanut allergy cohort. Hoxb8 MCs were passively sensitized with sera from peanut-allergic and peanut tolerant children and adolescents (n = 112). Degranulation of Hoxb8 MCs was quantified upon stimulation with dose-titrated peanut extract by means of flow cytometry, using CD107a as activation marker. The results from the Hoxb8 mast cell activation test (Hoxb8 MAT) were compared to established diagnostic assays such as the skin prick test (SPT), specific IgE (sIgE) levels, and the basophil activation test (BAT). Additionally, serum samples from BAT nonresponders were assessed with the Hoxb8 MAT. Hoxb8 MAT displayed a robust dose-dependent activation to peanut extract, with a cutoff value of ≤5.2% CD107a positive cells. The diagnostic accuracy was highest at allergen concentrations ≥100 ng/mL, with an area under the receiver operating characteristic curve (AUROC) of 0.97, 93% sensitivity, and 96% specificity, outperforming traditional SPT and sIgE tests. When compared to BAT, Hoxb8 MAT exhibited comparable diagnostic efficacy. Moreover, sera from BAT nonresponders were accurately classified into allergics and nonallergics by the Hoxb8 MAT. The Hoxb8 MAT demonstrated a very good diagnostic precision in patients prospectively assessed for peanut allergy comparable to the fresh whole blood-based BAT. Additionally, it demonstrated its value for accurate classification of BAT nonresponders into allergic and nonallergic individuals. Further investigations into its utility in the routine clinical setting are warranted.

A real-world data analysis of distribution and inconsistency between total serum IgE and allergen-specific IgE results in clinical practice.

The inconsistency between serum total IgE (tIgE) and allergen-specific IgE (sIgE) results is often encountered in clinical practice, but the distribution and influencing factors of the inconsistent results have not been fully understood. The aim of this study was to analyze the distribution and inconsistency between tIgE and sIgE test results. A retrospective study, from the electronic medical records of 2139 patients who underwent both tIgE and sIgE tests, from January to December 2023 was reviewed. The tIgE and sIgE results and their distribution, as well as their inconsistency, were analyzed based on sex, age, and disease subgroups. 36.2% of the patients had a positive sIgE, and 43.7% had an elevated tIgE level. sIgE and tIgE results were discordant in nearly 30% of patients, with no difference between genders, while individuals aged over 60 exhibited a significantly higher inconsistency rate than the other age groups, and the inconsistency rate between tIgE and sIgE results was significantly different among different tIgE levels, sIgE grades, positive allergen count and positive allergen types. In addition, patients with chronic urticaria (CU) had a higher inconsistency rate than those with other allergic diseases, but the difference was not statistically significant. The overall inconsistency rate between tIgE and sIgE results was about 30%. The elderly group older than 60 years old is more likely to have inconsistent results, and tIgE level, sIgE level, the number and type of positive allergens also affected the consistency of tIgE and sIgE results.

Optimization of Basophil Activation Test in the Diagnosis and Qualification for Allergen-Specific Immunotherapy in Children with Respiratory Allergy to the House Dust Mite Dermatophagoides pteronyssinus.

The aim of this study was to optimize a basophil activation test in the detection of allergy to the house dust mite Dermatophagoides pteronyssinus in children with allergic respiratory diseases. This study involved 32 cases, 13 girls and 19 boys aged 4-17 years, with perennial asthma or allergic rhinitis caused by D. pteronyssinus. The control group consisted of 13 girls and 19 boys aged 4-17 years with seasonal allergic asthma or rhinitis provoked by Timothy or birch pollen. House dust mite (HDM) allergy was excluded in the controls based on their medical history, skin prick test (SPT) results and sIgE determination. In all patients, a basophil activation test (BAT) was performed with five dilutions of D. pteronyssinus allergen (the dilution series ranged from 22.5 to 0.00225 ng/mL). The results were analyzed by using the receiver operating characteristics (ROC) to determine the optimal allergen concentrations, outcome measures and cut-off points that would differentiate most accurately between HDM-allergic and non-allergic patients. As a "gold standard", criteria for allergen-specific immunotherapy with D. pteronyssinus or respective pollens were applied by an experienced pediatric allergist following the guidelines of the European Academy of Allergy and Clinical Immunology. The highest diagnostic efficiency was yielded by the protocol assuming a cut-off value of 9.76% activated basophils after activation with a single allergen concentration of 2.25 ng/mL (sensitivity 90.6%, specificity 100%). This protocol yielded 3 (4.7%) misclassifications, all false negative, when compared with the "gold standard". There was a strong correlation with the BAT results at 22.5, 2.25 and 0.225 ng/mL (respectively r = 0.90 and r = 0.78, p < 0.001), as well as between the BAT at 2.25 ng/mL and SPT (r = 0.82, p < 0.001) and between the SPT and sIgE levels (r = 0.78, p < 0.001). High cross-reactivity between D. pteronyssinus and D. farinae was confirmed based on the BAT at 22.5 ng/mL (r = 0.82, p < 0.001). In conclusion, the BAT showed very good concordance with the result of a meticulous process of decision-making that combined validated allergy tests (SPT, sIgE) with expert guidelines, specialist knowledge and experience. Facing the risk of the incorrect qualification of patients for costly, long-lasting and potentially risky allergen-specific immunotherapy, the inclusion of a basophil activation test into diagnostic process seems fully justified.

Mapping of IgE cross-reactivity of Gly m 4, Gly m 5 and Gly m 6 soybean allergens in patients with atopic diseases

Currently, a significant portion of the food consists of multiple different ingredients. Soybean proteins have been widely used for production of these combined foodstuffs. Meanwhile, soy proteins may contain a wide range of allergens, and even, if present in small amounts, they can cause severe allergic reactions due to cross-reactivity. The aims of our study were to evaluate the prevalence of sensitization to soybean allergen components Gly m 4, Gly m 5 and Gly m 6, and to map their IgE cross-reactivity with homologous proteins of Bet v1-like proteins and cupin proteins in patients with atopic disorders. We have studied IgE’s to 112 allergenic components of plant and animal origin in blood sera from 54 patients with history of allergy, using the ImmunoCap ISAC method. The results were analyzed by means of MS Excel program using parametric statistical criteria. Results: In patients with atopic diseases, we have detected serum IgE to the rGly m 4 allergic component (5 patients out of 29; 17.24%). Frequency of sIgE detection to rGly m 5 (3 patients of 29; 10.24%) and rGly m 6 (1 patient of 29; 3.44%) was less pronounced. Cross-reactive sIgE was detected only to allergens of the Bet v1 superfamily. The strongest relationship was found between sIgE level to rGly m 4 and rBet v1 (R = 0.68; p = 0.001). Another IgE cross-reaction was found between soybean rGly m 4 and alder pollen rAln g1 (R = 0.681; p = 0.000). IgE antibodies to rGly m 4 may also cross-react with kiwi rAct d8 (R = 0.59; p = 0.001). We have also found a weak correlation between sIgE to soybean rGly m 4 and two hazelnut rCor a1 isoforms: rCor a 1.01 (R = 0.42; p = 0.023), and rCor a 1.04 (R = 0.39; p = 0.036). The IgE cross-reactivity profile of the soy allergens revealed in this study is important for improvement of testing strategy for the presence of causally significant allergens. This finding will help to avoid the development of hidden cross-reactions that trigger both oral and respiratory allergic processes in subjects with allergic pathology. Moreover, this will enable administration of optimal diets and develop technologies for development of hypoallergenic food products.

Only repeatedly elevated IgG4 levels in primary sclerosing cholangitis may distinguish a particular patient phenotype

BackgroundPrimary sclerosing cholangitis (PSC) is a chronic liver disease leading to inflammation with scaring and strictures of bile ducts, which can lead to liver cirrhosis. A subtype of PSC characterized by high serum IgG4 (sIgG4) levels has been reported to be associated with poor outcomes, but the exact role and the longitudinal development of sIgG4 levels in PSC progression remains to be clarified. The aim of this study was to investigate if subsequent analysis of sIgG4 levels allows the identification of the PSC phenotype with high sIgG4.MethodssIgG4 values were repeatedly analysed in a well-characterized European PSC cohort of 110 individuals. Biochemical parameters, clinical endpoints, death and liver transplantation were compared between PSC subgroups.Results12.7% (n = 14) of PSC patients showed increased sIgG4 levels (PSC-IgG4). The values normalized in 57.1% (n = 8; PSC-IgG4norm) during follow-up measurements, whereas the values remained permanently elevated in 42.9% (n = 6; PSC-IgG4const). Serum values of AP and γGT were significantly higher in PSC-IgG4const compared to PSC-IgG4norm at final blood sampling. Furthermore, mean age at PSC diagnosis was markedly lower in PSC-IgG4const compared to PSC-IgG4norm.ConclusionsThis is the first study analyzing longitudinal development of sIgG4 in PSC. Our data indicate that only sequential determination of sIgG4 levels allow to accurately distinguish between the PSC phenotype with high sIgG4 and PSC with low sIgG4.Graphical abstract

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

It has been suggested that genetic factors may be substantially linked to allergy disorders. 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. 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. 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). 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.

Augmented type 2 inflammatory response in allergic rhinitis patients experiencing systemic reactions to house dust mite subcutaneous immunotherapy.

Subcutaneous immunotherapy (SCIT) can induce systemic reactions (SRs) in certain patients, but the underlying mechanisms remain to be fully elucidated. AR patients who were undergoing standardized HDM SCIT (Alutard, ALK) between 2018 and 2022 were screened. Those who experienced two consecutive SRs were included in the study group. A control group was established, matched 1:1 by gender, age, and disease duration with the study group, who did not experience SRs during SCIT. Clinical and immunological parameters were recorded and analyzed both before SCIT and after 1 year of treatment. A total of 161 patients were included, with 79 (49.07%) in the study group. The study group had a higher proportion of AR combined asthma (26.8% vs. 51.8%, p < 0.001) and higher levels of sIgE to HDM and HDM components (all p < .001). Serum IL-4 and IL-13 levels in the study group were higher than those in the control group (p < .05). The study group received a lower maintenance dosage of HDM extracts injections than control group due to SRs (50000SQ vs. 100000SQ, p < .05). After 1 year of SCIT, the VAS score, the lung function parameters of asthmatic patients over 14 years old significantly improved in both groups (all p < .05). After a 7-day exposure to 20 μg/mL HDM extracts, the percentages of Th1, Th17, Tfh10, and Th17.1 in PBMCs decreased, while the Tfh13 cells significantly increased in the study group (p < .05). The type 2 inflammatory response is augmented in HDM-induced AR patients who experienced SRs during SCIT. Despite this, SCIT remains effective in these patients when administered with low-dosage allergen extracts.

Detection of Specific IgE against Molds Involved in Allergic Bronchopulmonary Mycoses in Patients with Cystic Fibrosis.

Allergic bronchopulmonary mycoses (ABPM) can be due to molds other than Aspergillus fumigatus in patients with cystic fibrosis (pwCF). We aimed to develop immunoassays for the detection of specific IgE (sIgE) directed against five fungal species involved in ABPM: Aspergillus terreus, Scedosporium apiospermum, Lomentospora prolificans, Rasamsonia argillacea, and Exophiala dermatitidis. Serum samples (n = 356) from 238 pwCF, collected in eight CF care centers in France, Germany, and Italy, were analyzed by dissociated enhanced lanthanide fluorescent immunoassay (DELFIA®) to assess levels of sIgE directed against antigenic extracts of each fungus. Clinical, biological, and radiological data were collected for each episode. One hundred serum samples from healthy blood donors were used as controls. Sera were classified into four groups depending on the level of sIgE according to the quartile repartition calculated for the pwCF population. A score of 4 for values above the 3rd quartile corresponds to an elevated level of sIgE. PwCF showed higher levels of sIgE than controls. Based on criteria from the ABPA-ISHAM working group, with an additional criterion of "a sIgE score of 4 for at least one non-A. fumigatus mold", we were able to diagnose six cases of ABPM. Using 417IU/mL as the threshold for total IgE and the same additional criterion, we identified seven additional pwCF with "putative ABPM". Detection of sIgE by DELFIA® showed good analytical performance and supports the role played by non-A. fumigatus molds in ABPM. However, commercially available kits usable in routine practice are needed to improve the diagnosis of ABPM.

Routinely Used and Emerging Diagnostic and Immunotherapeutic Approaches for Wheat Allergy.

Wheat, a component of the staple diet globally, is a common food allergen in children. The symptoms of wheat allergy (WA) range from skin rash to shortness of breath, significantly impairing quality of life. Following initial clinical suspicion, individuals may undergo routinely used allergy tests such as a wheat allergen-specific skin prick test (SPT), a blood test for specific immunoglobulin E (sIgE) levels, or oral food challenge. Conventional management of WA lies in wheat avoidance, yet accidental consumption may be inevitable owing to the ubiquity of wheat in various food products. This article aims to provide an overview of the immunologic pathway of WA, followed by its emerging diagnostic methods, namely alcohol-soluble SPT extracts, component-resolved diagnosis, and the basophil activation test (BAT). The mechanisms underlying wheat allergen-specific oral immunotherapy (OIT) as well as a summary of the efficacy, tolerability, and safety of related clinical trials will then be discussed.

Clinical features, severity, and immunological changes during venom immunotherapy in children and adults.

Background: Hymenoptera venom allergy (HVA) is among the most common causes of severe allergic reactions worldwide. Objective: To investigate clinical features and factors that affect the severity of HVA and to determine the alterations in immunologic biomarkers after venom immunotherapy (VIT). Methods: Seventy-six adults and 36 children were prospectively investigated. We analyzed specific immunoglobulin E (sIgE) and sIgG4 levels of venom extracts and components (rApi m1, rApi m10, rVes v1, rVes v5, rPol d5) before and after the first year of VIT. Results: Although cardiovascular symptoms were more common in adults (p < 0.001), the skin was the most affected organ in children (p = 0.009). Serum basal tryptase (sBT) levels were higher in the adults than the children (p < 0.001). The absence of urticaria (odds ratio [OR] 4.208 [95% confidence interval {CI}, 1.395-12.688]; p = 0.011) and sBT ≥ 5.2 ng/mL (OR 11.941 [95% CI, 5.220-39.733]; p < 0.001) were found as the risk factors for grade IV reactions. During VIT, changes in sIgE levels were variable. In the Apis VIT group, we observed remarkable increases in sIgG4 levels in Apis extract and rApi m1 but not in Api m10. Vespula extract, rVes v1, and rVes v5 sIgG4 levels were significantly increased in Vespula VIT group, we also detected significant increases in the Polistes extract and rPol d5 sIgG4 levels, which were not observed in the Apis VIT group. In the patients who received both Apis and Vespula VIT, increases in sIgG4 levels were observed for both venoms. Conclusion: Adults and children can have different clinical patterns. After 1 year, VIT induced a strong IgG4 response. Although Apis immunotherapy (IT) induced Apis sIgG4, excluding Api m10, Vespula IT induced both Vespula and Polistes sIgG4.

Immunological and molecular study in children with combined immunodeficiency.

Background. Severe combined immunodeficiency (SCID) is a form of immunodeficiencies (PID), caused by molecular defects. These defects can restrict the development and function of lymphocytes. Early diagnosis and treatment of SCID can lead to disease-free survival. This study aims to investigate some of the possible underlying genetic defects in a group of Egyptian infants and children with clinical and immunological profiles suggestive of SCID. Methods. This study included eighty patients who showed clinical warning signs of immunodeficiency. Subjects were thoroughly examined clinically. Laboratory evaluation included immunoglobulins serum levels and flow cytometric assessment of immune cells. This testing showed an altered immune profile in thirty patients. They had decreased T and/or B lymphocytes or natural killer cells. DNA extraction was done for those cases. The coding regions of the RAG1 gene and RAG2 gene was investigated for hot spot mutations by sequencing technique guided by the patient clinical evaluation, inheritance pattern, immunophenotyping by flow cytometric analysis of lymphocyte subsets, and serum immunoglobulins level detection. Results. Results showed novel and previously reported variants (mutation, polymorphism), they were found in 18 cases which include variants in the RAG1 gene (E880K, A960A, H249R, S913R, K820R, V782G), and variants in the RAG2 gene (P501T, L514M, rs10836573, cDNA.2129A>T). Conclusions. To evaluate SCID patients completely, mutation gene analysis is highly required and recommended.

Atopic diseases-Diagnostics, mechanisms, and exposures.

Epidemiological data suggest that atopic diseases begin in early life and that most cases present clinically during early childhood. The diseases are highly prevalent and increase as communities adopt western lifestyles. Disentangling the pathophysiological mechanisms leading to disease debut is necessary to identify beneficial/harmful exposures so that successful prevention and treatment can be generated. The objective of this review is to explore the definition of atopy and mechanisms of atopic diseases, and to investigate the importance of environmental factors in early life, prior to disease development. First, the distribution of sIgE levels in children is investigated, as this is one of the main criteria for the definition of atopy. Thereafter, it is explored how studies of parental atopic status, sensitization patterns, and early debut and severity of atopic dermatitis have substantiated the theory of an early-life window of opportunity for intervention that precedes the development of atopic diseases in childhood. Then, it is examined whether early-life exposures such as breastfeeding, dogs, cats, and house dust mites in the home perinatally constitute important influencers in this crucial time of life. Finally, it is discussed how these findings could be validated in randomized controlled trials, which might prepare the ground for improved diagnostics and prevention strategies to mitigate the current atopic pandemic.