IgE, IgE Receptors and Anti-IgE Biologics: Protein Structures and Mechanisms of Action.

The evolution of IgE in mammals added an extra layer of immune protection at body surfaces to provide a rapid and local response against antigens from the environment. The IgE immune response employs potent expulsive and inflammatory forces against local antigen provocation, at the risk of damaging host tissues and causing allergic disease. Two well-known IgE receptors, the high-affinity FcεRI and low-affinity CD23, mediate the activities of IgE. Unlike other known antibody receptors, CD23 also regulates IgE expression, maintaining IgE homeostasis. This mechanism evolved by adapting the function of the complement receptor CD21. Recent insights into the dynamic character of IgE structure, its resultant capacity for allosteric modulation, and the potential for ligand-induced dissociation have revealed previously unappreciated mechanisms for regulation of IgE and IgE complexes. We describe recent research, highlighting structural studies of the IgE network of proteins to analyze the uniquely versatile activities of IgE and anti-IgE biologics.

Airway Epithelial Cell-Derived Colony Stimulating Factor-1 Promotes Allergen Sensitization.

Airway epithelial cells (AECs) secrete innate immune cytokines that regulate adaptive immune effector cells. In allergen-sensitized humans and mice, the airway and alveolar microenvironment is enriched with colony stimulating factor-1 (CSF1) in response to allergen exposure. In this study we found that AEC-derived CSF1 had a critical role in the production of allergen reactive-IgE production. Furthermore, spatiotemporally secreted CSF1 regulated the recruitment of alveolar dendritic cells (DCs) and enhanced the migration of conventional DC2s (cDC2s) to the draining lymph node in an interferon regulatory factor 4 (IRF4)-dependent manner. CSF1 selectively upregulated the expression of the chemokine receptor CCR7 on the CSF1R+ cDC2, but not the cDC1, population in response to allergen stimuli. Our data describe the functional specification of CSF1-dependent DC subsets that link the innate and adaptive immune responses in T helper 2 (Th2) cell-mediated allergic lung inflammation.

Integrin ß1-mediated mast cell immune-surveillance of blood vessel content.

BACKGROUND: IgE-mediated degranulation of mast cells (MCs) provides rapid protection against environmental hazards, including animal venoms. A fraction of tissue-resident MCs intimately associates with blood vessels. These perivascular MCs were reported to extend projections into the vessel lumen and to be the first MCs to acquire intravenously injected IgE, suggesting that IgE loading of MCs depends on their vascular association. OBJECTIVE: We sought to elucidate the molecular basis of the MC-blood vessel interaction and to determine its relevance for IgE-mediated immune responses. METHODS: We selectively inactivated the Itgb1 gene, encoding the ß1 chain of integrin adhesion molecules (ITGB1), in MCs by conditional gene targeting in mice. We analyzed skin MCs for blood vessel association, surface IgE density, and capability to bind circulating antibody specific for MC surface molecules, as well as in vivo responses to antigen administered via different routes. RESULTS: Lack of ITGB1 expression severely compromised MC-blood vessel association. ITGB1-deficient MCs showed normal densities of surface IgE but reduced binding of intravenously injected antibodies. While their capacity to degranulate in response to IgE ligation in vivo was unimpaired, anaphylactic responses to antigen circulating in the vasculature were largely abolished. CONCLUSIONS: ITGB1-mediated association of MCs with blood vessels is key for MC immune surveillance of blood vessel content, but is dispensable for slow steady-state loading of endogenous IgE onto tissue-resident MCs.

IgE directly affects eosinophil migration in chronic rhinosinusitis with nasal polyps through CCR3 and predicts the efficacy of omalizumab.

BACKGROUND: Whether IgE affects eosinophil migration in chronic rhinosinusitis with nasal polyps (CRSwNP) remains largely unclear. Moreover, our understanding of local IgE, eosinophils, and omalizumab efficacy in CRSwNP remains limited. OBJECTIVE: We investigated whether IgE acts directly on eosinophils and determined its role in omalizumab therapy. METHODS: Eosinophils and their surface receptors were detected by hematoxylin and eosin staining and flow cytometry. IgE and its receptors, eosinophil peroxidase (EPX), eosinophilic cationic protein, and CCR3 were detected by immunohistochemistry and immunofluorescence. Functional analyses were performed on blood eosinophils and polyp tissues. Logistic regression was performed to screen for risk factors. Receiver operating characteristic curve was generated to evaluate the accuracy. RESULTS: Both FcεRI and CD23 were expressed on eosinophils. The expression of FcεRI and CD23 on eosinophil in nasal polyp tissue was higher than in peripheral blood (both P < .001). IgE and EPX colocalized in CRSwNP. IgE directly promoted eosinophil migration by upregulating CCR3 in CRSwNP but not in healthy controls. Omalizumab and lumiliximab were found to be effective in restraining this migration, indicating CD23 was involved in IgE-induced eosinophil migration. Both IgE+ and EPX+ cells were significantly reduced after omalizumab treatment in those who experienced response (IgE+ cells, P = .001; EPX+ cells, P = .016) but not in those with no response (IgE+ cells, P = .060; EPX+ cells, P = .151). Baseline IgE+ cell levels were higher in those with response compared to those without response (P = .024). The baseline local IgE+ cell count predicted omalizumab efficacy with an accuracy of 0.811. CONCLUSIONS: IgE directly promotes eosinophil migration, and baseline local IgE+ cell counts are predictive of omalizumab efficacy in CRSwNP.

IgE to cyclophilins in pollen-allergic children: Epidemiologic, clinical, and diagnostic relevance of a neglected panallergen.

BACKGROUND: Cyclophilins are ubiquitous panallergens whose epidemiologic, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice. OBJECTIVE: We investigated the epidemiologic, diagnostic, and clinical relevance of cyclophilins in seasonal allergic rhinitis and its comorbidities. METHODS: We examined a random sample of 253 (25%) of 1263 Italian children with seasonal allergic rhinitis from the Panallergens in Pediatrics (PAN-PED) cohort with characterized disease phenotypes. Nested studies of sensitization prevalence, correlation, and allergen extract inhibition were performed in patients sensitized to birch pollen extract but lacking IgE to Bet v 1/2/4 (74/1263) or with highest serum level of IgE to Bet v 1 (26/1263); and in patients with sensitization to various extracts (ragweed, mugwort, pellitory, Plantago, and plane tree), but not to their respective major allergenic molecule, profilins, and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7, and extract inhibition tests were performed with the same rBet v 7. RESULTS: IgE to rBet v 7 was detected in 43 (17%) of 253 patients. It was associated with asthma (P < .028) and oral allergy syndrome (P < .017) in univariate but not multivariate analysis adjusted for IgE to profilins (Phl p 12), PR-10s (Bet v 1), and lipid transfer proteins (Pru p 3). IgE to rBet v 7 was also highly prevalent (47/74, 63%) among patients with unexplained sensitization to birch pollen extract. In patients with unexplained sensitization to ragweed, mugwort, pellitory, Plantago and plane tree pollen, the levels of IgE to those extracts correlated with the levels of IgE to rBet v 7, and they were also significantly inhibited by rBet v 7 (inhibition range 45%-74%). CONCLUSIONS: IgE sensitization to cyclophilin is frequent in pollen-allergic patients living in temperate areas and can produce "false" positive outcomes in skin prick and IgE tests to pollen extracts. Molecular diagnostic guidelines should include this panallergen family.

Novel machine learning method allerStat identifies statistically significant allergen-specific patterns in protein sequences.

Cutting-edge technologies such as genome editing and synthetic biology allow us to produce novel foods and functional proteins. However, their toxicity and allergenicity must be accurately evaluated. It is known that specific amino acid sequences in proteins make some proteins allergic, but many of these sequences remain uncharacterized. In this study, we introduce a data-driven approach and a machine-learning method to find undiscovered allergen-specific patterns (ASPs) among amino acid sequences. The proposed method enables an exhaustive search for amino acid subsequences whose frequencies are statistically significantly higher in allergenic proteins. As a proof-of-concept, we created a database containing 21,154 proteins of which the presence or absence of allergic reactions are already known and applied the proposed method to the database. The detected ASPs in this proof-of-concept study were consistent with known biological findings, and the allergenicity prediction performance using the detected ASPs was higher than extant approaches, indicating this method may be useful in evaluating the utility of synthetic foods and proteins.

The genome-wide association study of serum IgE levels demonstrated a shared genetic background in allergic diseases.

Immunoglobulin E (IgE) synthessis is highly related to a variety of atopic diseases, and several genome-wide association studies (GWASs) have demonstrated the association between genes and IgE level. In this study, we conducted the largest genome-wide association study of IgE involving a Taiwanese Han population. Eight independent variants exhibited genome-wide significance. Among them, an intronic SNP of CD28, rs1181388, and an intergenic SNP, rs1002957030, on 11q23.2 were identified as novel signals for IgE. Seven of the loci were replicated successfully in a meta-analysis using data on Japanese population. Among all the human leukocyte antigen (HLA) regions, HLA-DQA1*03:02 - HLA-DQB1*03:03 was the most significant haplotype (OR = 1.25, SE = 0.02, FDR = 1.6 × 10-14), corresponding to HLA-DQA1 Asp160 and HLA-DQB1 Leu87 amino acid residues. The genetic correlation showed significance between IgE and allergic diseases including asthma, atopic dermatitis, and pollinosis. IgE PRS was significantly correlated with total IgE levels. Furthermore, the top decile IgE polygenic risk score (PRS) group had the highest risk of asthma for the Taiwan Biobank and Biobank Japan cohorts. IgE PRS may be used to aid in predicting the occurrence of allergic reactions before symptoms occur and biomarkers are detectable. Our study provided a more comprehensive understanding of the impact of genomic variants, including complex HLA alleles, on serum IgE levels.

Targeting glycogen synthase kinase 3 with CHIR99021 negatively regulates allergen-induced mast cell activation.

Mast cells are granulated immune sentinels responsible for allergic inflammation. Allergen-induced FcεRI-signaling leads to rapid degranulation in the early-phase and sustained production and release of pro-inflammatory mediators in the late phase. Glycogen synthase kinase 3 (GSK3) is a constitutively active serine/threonine kinase and a central molecular convergence point for several pro-inflammatory pathways. GSK3 inhibition has been shown to reduce inflammation but has not yet been fully characterized in mast cell activation. Therefore, the objective of this study was to evaluate GSK3 as a putative therapeutic target in allergic inflammation using the GSK3 inhibitor, CHIR99021. Here, we found that GSK3 inhibition impaired ROS production and degranulation. Through modulation of MKK4-JNK, c-jun, and NF-κB signaling, GSK3 inhibition reduced the production/release of IL-6, IL-13, TNF, and CCL1, while only the release of CCL2 and CCL3 was impaired. Furthermore, CHIR99021-mediated GSK3 inhibition altered the pro-inflammatory phenotype of mast cells, reducing c-kit receptor levels. This implicated GSK3 in FcεRI signaling, reducing release of IL-6, TNF, and CCL1 when stimulated through FcεRI, while CCL2 and CCL3 remained unaffected, and were increased when stimulated with SCF only. These results identify GSK3 as a potential therapeutic target of utility warranting further consideration in contexts of pathological mast cell activation.

Comparison of the General Characteristics of Patients with Severe Asthma Who Switched from Omalizumab to Mepolizumab versus Patients Who Responded to Omalizumab Treatment: A Real-Life Study.

INTRODUCTION: Severe asthma is characterized by frequent recurrent airway symptoms and exacerbations, and these affect the quality of life. Biological agents can be used in the treatment of patients with severe asthma if the disease cannot be controlled with standard controller treatment. The aim of this study was to compare the clinical characteristics and laboratory data of patients with severe asthma who were switched from omalizumab to mepolizumab and patients with severe asthma who responded to omalizumab. METHODS: The clinical characteristics and laboratory data of patients with severe asthma who responded to omalizumab and switched from omalizumab to mepolizumab were compared retrospectively. RESULTS: Evaluation was made of a total of 79 patients, including 64 omalizumab responders and 15 who switched to mepolizumab from omalizumab. After omalizumab and mepolizumab treatment, the annual number of asthma attacks, the use of oral corticosteroid (OCS), the annual number of hospitalizations, and the eosinophil count significantly decreased (omalizumab: p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively; mepolizumab: p = 0.001, p = 0.001, p = 0.002, p = 0.001, respectively). After omalizumab treatment, the increase in forced expiratory volume in 1 s (FEV1) (%) and asthma control test (ACT) score were determined to be statistically significant (p < 0.001, p < 0.001, respectively). After mepolizumab treatment, the increase in ACT score was significant (p = 0.003). Drug allergy, chronic sinusitis with nasal polyps (CRSwNP), regular use of OCS, and high baseline eosinophil count (cells/µL) were associated with poor response to omalizumab treatment (odds ratio [OR] = 7.86, p = 0.003; OR = 52.92, p < 0.001; OR = 10.16, p = 0.004; OR = 0.99, p = 0.004, respectively). House dust mite sensitivity and high baseline FEV1 (%) were associated with good response to omalizumab treatment (OR = 0.29, p = 0.041; OR = 1.06, p = 0.03, respectively). The blood eosinophil count had diagnostic value in predicting the nonresponsiveness to omalizumab treatment (area under the curve [AUC]: 0.967, p < 0.001, cut-off: 510). CONCLUSION: A high pretreatment eosinophil count, concomitant CRSwNP, a history of drug allergy, and regular OCS use may be associated with poor response to omalizumab treatment in patients with severe asthma. Depending on the treatment response, treatment switching can be applied between biological agents. The results of the current study should be supported by multicenter studies.

The Sensitization Differences of Pollen Allergen Components in Patients with Asthma and/or Rhinitis in Southern China.

INTRODUCTION: This study aim to analyzed the main pollen allergen components that cause allergic asthma and/or rhinitis and the cross-reactions between the allergen components. METHODS: Twenty one allergic rhinitis patients and 23 allergic asthma patients with pollen sensitization from the China Biological Information Repository of Respiratory Diseases were included. All the patients were detected serum pollen allergens components specific immunoglobulin E (sIgE) including Betula verrucosa (Bet v 1, Bet v 2, Bet v 4), Quercus alba (Pla a 1, Pla a 2), Ambrosia elatior (Amb a 1), Artemisia vulgaris (Art v 1, Art v 3, Art v 4), Bermuda grass (Cyn d 1, Cyn d 12), Phleum pratense (Phl p 5, Phl p 1, Phl p 4, Phl p 7, Phl p 12), and cross-reactive carbohydrate determinants. RESULTS: In patients with asthma, Phl p 4 had the highest positive rate (60.9%), followed by Phl p 1 (43.5%) and Pla a 2 (34.8%), while in patients with rhinitis, Amb a 1 had the highest positive rate (71.4%), followed by Phl p 4 (61.9%) and Pla a 2 (42.9%). Meanwhile, Phl p 1 (43.5%) in asthma patients was higher than that in rhinitis (4.7%, p = 0.03), while Amb a 1 (71.4%) in rhinitis patients was higher than that in asthma (26.1%, p = 0.03). Interestingly, optimal scale analysis show that the severity of both asthma and rhinitis is related to Bet v 4 (Cronbach's Alpha = 95.0%). CONCLUSIONS: In general, Phl p 4 is the main allergenic component in pollen sensitized asthma patients, while Amb a 1 is the main allergenic component in pollen sensitized rhinitis patients. Sensitization to Bet v 4 may lead to more severe symptoms, and this result may be applied in future clinical precise diagnosis.

Identification and Characterization of Pectate Lyase as a Novel Allergen in Artemisia sieversiana Pollen.

INTRODUCTION: Artemisia species are widely spread in north hemisphere. Artemisia sieversiana pollen is one of the common pollen allergens in the north of China. At present, seven allergens were identified and had been listed officially from A. sieversiana pollen, but the remaining allergens are still insufficiently studied, which need to be found. METHODS: Pectate lyase was purified from the extracts of A. sieversiana pollen by anion exchange, size exclusion, and HPLC-hydrophobic interaction chromatography. The gene of A. sieversiana pectate lyase (Art si pectate lyase) was cloned and expressed in Escherichia coli. The enzyme activity and circular dichroism (CD) spectrum of natural and recombinant proteins were analyzed. The allergenicity of Art si pectate lyase was characterized by enzyme-linked immunosorbent assay (ELISA), Western blot, inhibition ELISA, and basophil activation test. The allergen's physicochemical properties, three-dimensional structure, sequence profiles with homologous allergens and phylogenetic tree were analyzed by in silico methods. RESULTS: Natural Art si pectate lyase (nArt si pectate lyase) was purified from A. sieversiana pollen extracts by three chromatographic strategies. The cDNA sequence of Art si pectate lyase had a 1191-bp open reading frame encoding 396 amino acids. Both natural and recombinant pectate lyase (rArt si pectate lyase) exhibited similar CD spectrum, and nArt si pectate lyase had higher enzymatic activity. Moreover, the specific immunoglobulin E (IgE) binding rate against nArt si pectate lyase and rArt si pectate lyase was determined as 40% (6/15) in patients' serum with Artemisia species pollen allergy by ELISA. The nArt si pectate lyase and rArt si pectate lyase could inhibit 76.11% and 47.26% of IgE binding activities to the pollen extracts, respectively. Art si pectate lyase was also confirmed to activate patients' basophils. Its structure contains a predominant motif of classic parallel helical core, consisting of three parallel ß-sheets, and two highly conserved features (vWiDH, RxPxxR) which may contribute to pectate lyase activity. Moreover, Art si pectate lyase shared the highest sequence identity of 73.0% with Art v 6 among currently recognized pectate lyase allergen, both were clustered into the same branch in the phylogenetic tree. CONCLUSION: In this study, pectate lyase was identified and comprehensively characterized as a novel allergen in A. sieversiana pollen. The findings enriched the allergen information for this pollen and promoted the development of component-resolved diagnosis and molecular therapy of A. sieversiana pollen allergy.

Immunoglobulin E-Mediated Food Sensitization in a Moroccan Pediatric Population with Celiac Disease.

INTRODUCTION: Celiac disease is a chronic autoimmune disorder that occurs following the ingestion of gluten, in genetically predisposed individuals. Patients with celiac disease, especially children, are likely prone to develop allergic reactions to different food allergens. However, the relationship between food allergy and celiac disease remains not elucidated. The aim of this pioneering study was to evaluate the prevalence of allergic food sensitization in children with celiac disease in Morocco. METHODS: A total of 57 children with confirmed celiac disease, including 25 males and 32 females with a mean age of 8.6 ± 4.4 years, underwent a food allergen-specific immunoglobulin E (IgE) screening. This screening was conducted using a multiparametric immunodot assay (Euroline Food "Maghreb," Euroimmun). Statistical analysis was performed using R software. RESULTS: Among the 57 cases tested, the overall rate of IgE-mediated sensitization to food allergens was found to be 48% (27/57), dominated by chicken, with 51.9% (14/27), followed by almond, 40.7% (11/27), sesame, 40.7% (11/27), potato 33.3% (9/27), and apple 18.5% (5/27). Of the s-IgE positive cases, 74% were sensitized at least to one allergen, 37% (10/27) were sensitized to both chicken and almond allergens. A significant correlation was observed between almond, sesame, chicken, and potato. CONCLUSION: The current study highlighted a high prevalence of food allergen sensitization in children with celiac disease. This underlines the potential benefit in screening for food allergy in celiac patients.

Associations between Total Immunoglobulin E Levels and Urinary Albumin Excretion: A Cross-Sectional Study.

INTRODUCTION: The association between total immunoglobulin E (IgE) levels and urinary albumin excretion has not been fully established. Current study aimed to evaluate the association between total IgE levels and urinary albumin-to-creatinine ratio (UACR) among adult Americans. METHODS: Current cross-sectional study utilized data from the 2005 to 2006 National Health and Nutrition Examination Survey, including individuals aged 20 years and above. To assess the relationships between total IgE levels and UACR, both multivariable linear regression models and smooth curve fitting were employed. RESULTS: The study included a total of 3,400 participants (weighted mean age: 46.6 ± 0.8 years), with 1,625 females (weighted percentage: 47.8%). After adjusting for potential confounders, we observed a positive association between higher total IgE levels on a log2 scale and increased UACR (ß = 3.34; 95% CI: 1.40-5.28, p = 0.002). Furthermore, the association displayed a non-linear dose-response pattern. The interaction test revealed a significant distinction in the correlation between total IgE and UACR when stratified by hyperlipidemia (p for interaction <0.001). The results remained robust in sensitivity analyses. CONCLUSION: Our study revealed a significant and independent association between elevated total IgE levels and an increased UACR, which also exhibited a distinct non-linear pattern, highlighting the intricate nature of the connection between IgE levels and UACR.

Peanut oral immunotherapy using an extensively heated and baked novel composition of peanuts.

BACKGROUND: Oral immunotherapy (OIT) is an increasingly acceptable therapeutic option for peanut-allergic (PA) children, despite significant side effects. Major peanut allergenic proteins are heat-resistant and are not rendered hypoallergenic after baking or cooking. Lyophilized peanut protein-MH (LPP-MH) is a novel composition from developing peanuts, enabling cooking-induced reduction in allergenicity. We aimed to explore the safety and efficacy of OIT, with extensively heated and baked (EHEB) LPP-MH in PA children. METHODS: In a single-arm, single-center, pilot study, PA children with a single highest tolerated dose of <100 mg peanut protein were placed on a 40-week OIT protocol with 300 mg daily of heat-treated LPP-MH. A repeat open peanut food challenge was performed after 40 weeks of treatment and at a 6-12 months of follow-up visit. RESULTS: Thirty-three children with PA were enrolled, with a mean cumulative tolerated dose (MCTD) of 71.2 mg PP (95% CI 45-100 mg). After 40 weeks, 32/33 patients were able to consume more than 300 mg of natural PP, with MCTD of 1709 mg (CI 365-3675 mg). There were no severe allergic reactions requiring epinephrine, during any of the observed LPP-MH challenges or any treatment related doses at home. After 6-12 months on daily maintenance, the MCTD was 8821 mg (95% CI 1930-13,500 mg). This enabled most children age-appropriate dietary inclusion of peanuts. CONCLUSION: An OIT protocol with heat-treated LPP-MH, a novel composition from developing peanuts, seems a potentially safe and efficacious OIT modality for PA children, enabling the introduction of dietary levels of peanut proteins in highly allergic PA children. Validation in randomized controlled studies is mandated.

Molecular allergology: a clinical laboratory tool for precision diagnosis, stratification and follow-up of allergic patients.

Identification of the molecular culprits of allergic reactions leveraged molecular allergology applications in clinical laboratory medicine. Molecular allergology shifted the focus from complex, heterogeneous allergenic extracts, e.g. pollen, food, or insect venom, towards genetically and immunologically defined proteins available for in vitro diagnosis. Molecular allergology is a precision medicine approach for the diagnosis, stratification, therapeutic management, follow-up and prognostic evaluation of patients within a large range of allergic diseases. Exclusively available for in vitro diagnosis, molecular allergology is nonredundant with any of the current clinical tools for allergy investigation. As an example of a major application, discrimination of genuine sensitization from allergen cross-reactivity at the molecular level allows the proper targeting of the culprit allergen and thus dramatically improves patient management. This review aims at introducing clinical laboratory specialists to molecular allergology, from the biochemical and genetic bases, through immunological concepts, to daily use in the diagnosis and management of allergic diseases.

Type 2 Biomarkers and Their Clinical Implications in Bronchiectasis: A Prospective Cohort Study.

PURPOSE: Bronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood. This study explores the clinical significance of these biomarkers in bronchiectasis patients. METHODS: In a cross-sectional cohort study, bronchiectasis patients, excluding those with asthma or allergic bronchopulmonary aspergillosis, underwent clinical and radiological evaluations. Bronchoalveolar lavage samples were analyzed for cytokines and microbiology. Blood eosinophil count (BEC), serum total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO) were measured during stable disease states. Positive type 2 biomarkers were defined by established thresholds for BEC, total IgE, and FeNO. RESULTS: Among 130 patients, 15.3% demonstrated BEC ≥ 300 cells/µL, 26.1% showed elevated FeNO ≥ 25 ppb, and 36.9% had high serum total IgE ≥ 75 kU/L. Approximately 60% had at least one positive type 2 biomarker. The impact on clinical characteristics and disease severity was variable, highlighting BEC and FeNO as reflective of different facets of disease severity and exacerbation risk. The combination of low BEC with high FeNO appeared to indicate a lower risk of exacerbation. However, Pseudomonas aeruginosa colonization and a high neutrophil-to-lymphocyte ratio (NLR ≥ 3.0) were identified as more significant predictors of exacerbation frequency, independent of type 2 biomarker presence. CONCLUSIONS: Our study underscores the distinct roles of type 2 biomarkers, highlighting BEC and FeNO, in bronchiectasis for assessing disease severity and predicting exacerbation risk. It advocates for a multi-biomarker strategy, incorporating these with microbiological and clinical assessments, for comprehensive patient management.

Clinical Presentation of Atopic Dermatitis.

Atopic dermatitis, commonly known as eczema, is a chronic inflammatory dermatosis that can affect individuals from infancy to adulthood. Also referred to as "the itch that rashes," atopic dermatitis is classically associated with significant pruritus that is accompanied by characteristic cutaneous and other clinical findings. The diagnosis of atopic dermatitis can be challenging due to the wide range of clinical presentations based on patient factors such as age, skin type, ethnicity, and other comorbid conditions. This chapter reviews the classical findings as well as the less common manifestations of atopic dermatitis.

Lipidomics reveals the serum profiles of pediatric allergic rhinitis and its severity.

Allergic rhinitis (AR) is a prevalent upper airway chronic inflammatory disease in children worldwide. The role of bioactive lipids in the regulation of AR has been recognized, but the underlying serum lipidomic basis of its pathology remains unclear. We utilized ultra-performance liquid chromatography (UPLC)-Q-Exactive Orbitrap/mass spectrometry (MS) to investigate the serum lipidomic profiles of children with AR. The lipidomic analysis identified 42 lipids that were differentially expressed (p < 0.05, fold change > 2) between the AR (n = 75) and normal control groups (n = 44). Specifically, the serum levels of diacylglycerol (DG), triacylglycerol (TG), fatty acid (FA), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine, phosphatidyl-ethanolamine, and cardiolipins were significantly higher in the AR group. The diagnostic potential of the identified lipids was further evaluated using receiver operating characteristic curve analysis. The analysis revealed that five lipids, including FA 30:7, LPC O-18:1, LPC 18:0, LPC 16:0, and DG 34:0, had area under the curve values greater than 0.9 (p < 0.05). Furthermore, serum levels of IgE and IL-33, markers of AR severity, were found to have a significant positive correlation (p < 0.05) with DGs, LPCs, TGs, and FAs in AR patients. This study revealed the lipid disorders associated with AR and its severity, providing new insights into the pathological process of AR.

Successful infliximab treatment in siblings with Netherton syndrome: Unveiling a novel SPINK5 gene variant and literature review.

Netherton syndrome (NS) is a rare autosomal recessive genodermatosis. In this article, we present two siblings with NS who harbour a novel variant in the SPINK5 gene and were treated with infliximab infusions. Both patients exhibited the characteristic clinical triad of NS, and their whole exome sequencing analysis revealed a homozygous variant, c.1820+53G>A, in the SPINK5 gene. Notably, this is the first documented instance of homozygosity for this particular variant. Despite the absence of a specific treatment, both patients achieved total clearance of the skin lesions, and a significant decrease in total IgE levels was documented.

Role of serum-specific immunoglobulin E in egg allergy: a comprehensive study of Portuguese pediatric patients.

INTRODUCTION: Food allergies represent a growing public health concern, particularly among children. This study aims to examine egg allergy in pediatric patients and analyze the value of serum-specific immunoglobulin E (sIgE) levels as predictive biomarkers for oral food challenge (OFC) outcomes. METHODS: Retrospective study, involving pediatric patients with suspected IgE-mediated egg allergy, conducted at a tertiary hospital. RESULTS: Data from 176 pediatric patients were analyzed, revealing a higher male prevalence (59.1%). Most cases (40.3%) presented symptoms in the first year of life, predominantly mucocutaneous symptoms (46%). OFC results varied across various forms of egg presentation, with cooked egg being the most frequently tested food. Positive OFCs were observed in 14.6% (n = 36) of cases. The study identified specific egg protein biomarkers for positive OFC, with ovalbumin for raw egg (sIgE > 1.28 KUA/L; area under the curve [AUC] = 0.917; sensitivity [S] 100%; and specificity [Sp] 92%), ovomucoid for cooked egg (sIgE > 0.99 KUA/L; AUC = 0.788, 95%; S: 79%; and Sp: 74%), and ovomucoid for baked egg (sIgE> 4.63 KUA/L; AUC = 0.870; S: 80%; and Sp: 85%) showing predictive capacities. CONCLUSIONS: The findings underscore the importance of considering various forms of egg presentation in the diagnosis and management of egg allergy. The findings highlight the valuable discriminatory capacity and provided reliable biomarkers, such as ovalbumin for raw egg and ovomucoid for cooked and baked egg in risk assessment, aiding in predicting OFC outcomes and helping clinicians to make informed decisions in diagnosing and managing egg allergies, thus improving patient care and quality of life.