Total Serum IgE Levels Research Articles

Immunoglobulin E autoantibodies in atopic dermatitis associate with Type-2 comorbidities and the atopic march.

Autoreactive immunoglobulin E (IgE) antibodies to self-peptides within the epidermis have been identified in patients with atopic dermatitis (AD). Prevalence, concomitant diseases, patient characteristics, and risk factors of IgE autoantibody development remain elusive. We aimed to determine IgE autoantibodies in serum samples (n = 672) from well-characterized patients with AD and controls (1.2-88.9 years). Atopic dermatitis patients were sub-grouped in AD with comorbid Type-2 diseases ("AD + Type 2"; asthma, allergic rhinitis, food allergy, n = 431) or "solely AD" (n = 115). Also, subjects without AD but with Type-2 diseases ("atopic controls," n = 52) and non-atopic "healthy controls" (n = 74) were included. Total proteins from primary human keratinocytes were used for the immunoassay to detect IgE autoantibodies. Values were compared to already known positive and negative serum samples. Immunoglobulin E autoantibodies were found in 15.0% (82/546) of all analyzed AD-patients. "AD + Type 2" showed a higher prevalence (16.4%) than "solely AD" (9.6%). "Atopic controls" (9.6%) were comparable with "solely AD" patients, while 2.7% of healthy controls showed IgE autoantibodies. Of those with high levels of IgE autoantibodies, 15 out of 16 were patients with "AD + Type 2". AD patients with IgE autoantibodies were younger than those without. Patients with IgE autoreactivity also displayed higher total serum IgE levels. Factors that affected IgE autoantibody development were as follows: birth between January and June, cesarean-section and diversity of domestic pets. Immunoglobulin E autoantibodies in AD seem to associate with the presence of atopic comorbidities and environmental factors. The potential value of IgE autoantibodies as a predictive biomarker for the course of AD, including the atopic march, needs further exploration.

The ratio of total IgE level at week 16 to baseline significantly correlated with the clinical response to omalizumab in moderate to severe allergic rhinitis patients

ObjectiveTo analyze whether the ratio of total IgE level at week 16 to baseline could be used as an indicator to evaluate clinical efficacy of patients treated with omalizumab. MethodsWe retrospectively analyzed the clinical characteristics of 62 patients with moderate-to-severe allergic rhinitis treated with omalizumab, and compared the pre-and post-treatment nasal visual analog scale (n-VAS) scores, the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Rhinitis Control Assessment Test (RCAT), improvement in nasal congestion, number of acute episodes of rhinitis, and total IgE levels in serum. The relationship between the efficacy of treatment with omalizumab and the change in total IgE levels before and after treatment was further analyzed. ResultsThis study included 62 patients with moderate-to-severe allergic rhinitis, of which 48 demonstrated significant improvement after 16 weeks of omalizumab therapy; the results of 16 weeks’ omalizumab treatment in 14 patients did not show significant improvements in allergic rhinitis symptoms based on RACT scores. After 16 weeks of omalizumab treatment, the RQLQ score decreased from (36.6 ± 13.7) at baseline level to (9.1 ± 12.6) after 16 weeks treatment.The ratio of total IgE at week 16 to total IgE levels at baseline was (2.9 ± 1.4) KU/L in 62 patients. And the ratio of total IgE levels at week 16 to total IgE levels at baseline was (3.3 ± 1.4) KU/L for responders and (1.6 ± 0.5) KU/L for non-responders. ConclusionThe ratio of total IgE level at week 16 to baseline significantly correlated with the clinical response to omalizumab in moderate to severe allergic rhinitis patients, when the ratio of total IgE level at week 16 to baseline was ≥2.0. Omalizumab effectively treated patients with moderate-to-severe allergic rhinitis, and improved their quality of life.

Association of Interleukin-4 in Immunoglobulin-E Mediated Asthma: A Cross Sectional Study

Backgrounds: Interleukin 4 (IL 4) is a cytokine associated with the cause of several allergic diseases such as asthma due to their function in the differentiation of T helper type 2 lymphocytes and induction of the IgE isotype switch. Object: The study aims to determine the association IL-4 level with total serum IgE levels and asthma severity. Methods: A cross-section study was performed. Eighty-seven subjects were recruited from Karbala Teaching Hospital for Children in the period extending from January 25 to May 24, 2022, including children with asthma, were subjected to measure IL 4 level using Elabscience ELISA kit and measured total IgE level using AccuBind IgE ELISA kit. Results: Eighty-seven subjects of asthmatic children in which the mean age was 7.833 ± 3.652. There are 65.52% and 34.48% of asthmatic children (male and female, respectively). Total serum IgE was 398.889 ± 227.156 IU/ml, while the IL-4 level was 5.18 ± 8.224. There was a significant difference in IL 4 levels depending on asthma severity (P= 0.037). IL-4 levels in severe persistent asthma were higher than IL-4 levels in mild and moderate persistent asthma. Further, there was a highly significant difference in IL 4 levels depending on asthma controlled (P= 0.004). IL-4 levels in not well-controlled asthma were higher than IL-4 levels in well and partial controlled asthma. In addition, there was no significant correlation between IL-4 levels and total serum IgE levels (P=0.436). Conclusion: IL 4 has an important role in predicting asthma severity and asthma control in children. These findings have important implications for the treatment of IgE-mediated asthma. Despite this, IL 4 levels have no significant correlation with total serum IgE levels. J MEDICINE 2023; 24(2): 89-95

NLRP3 inflammasome (rs10754558) gene polymorphism in patients with atopic dermatitis

The nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome is a high molecular weight protein complex that has been linked to a variety of allergic and inflammatory disorders in humans, including atopic dermatitis (AD). Polymorphisms in NLRP3 genes could lead to immune dysregulation. This case-control study aimed to assess the association between NLRP3 inflammasome (rs10754558) gene polymorphism in AD and the incidence and severity of the disease. We included 62 subjects in each of the AD and control groups. Serum total IgE levels and NLRP3 inflammasome (rs10754558) gene polymorphism were assessed and compared between the two study groups and among the AD group as arranged by disease severity. The AD group showed significantly higher levels of serum total IgE compared to controls (p˂0.001). Serum IgE levels were also significantly associated with AD severity. The (rs10754558) G allele was significantly predominant among AD participants (OR: 2.33; 95% CI: 1.1 -4.92) and 51.6% of the AD group was carriers of the GG genotype. Moreover, there was a substantial correlation between NLRP3 (rs10754558) G allele and AD score index for disease severity (OR: 7.17; 95% CI: 1.47 – 35.7). In conclusion, NLRP3 inflammasome (rs10754558) gene polymorphism G allele could be an important factor in the predisposition and exacerbation of AD.

410 Dupilumab treatment reduces total IgE levels in patients 6 months and older with moderate-to-severe atopic dermatitis

Abstract Atopic dermatitis (AD) is a type 2 inflammatory disease characterized by elevations in several biomarkers including serum IgE—a key downstream mediator in the type 2 adaptive immune response. Patients with moderate-to-severe AD were enrolled for 16 weeks in any of six randomized, placebo-controlled, phase 3 studies: in LIBERTY AD PRESCHOOL, (NCT03346434 part B) patients aged 6 months to 5 years were treated with dupilumab 200/300 mg every 4 weeks (q4w) + topical corticosteroids (TCS; n = 83) or placebo + TCS (n = 79); in LIBERTY AD PEDS (NCT03345914), patients aged 6–11 years were treated with dupilumab + TCS [100/200 mg q2w (n = 122), 300 mg q4w (n = 122)] or placebo + TCS (n = 123); in LIBERTY AD ADOL (NCT03054428), patients aged 12–17 years were treated with dupilumab [200/300 mg q2w (n = 82), 300 mg q4w (n = 83)] or placebo (n = 85); and in LIBERTY AD CHRONOS/SOLO1/SOLO2 (NCT02260986/NCT02277743/NCT02277769, pooled), patients aged ≥18 years were treated with dupilumab [300 mg q2w (n = 563),300 mg qw (n = 781) ] or placebo (n = 775). The TCS were allowed in CHRONOS only. At Week 16, dupilumab treatment significantly (P < 0.0001) reduced median total serum IgE levels [kU/L (IQR)] compared with placebo in patients aged 6 months to 5 years [843 (207–3300) vs. 3625 (540.5–8585)], 6–11 years [1519 (532–3808) vs. 3862 (1166–9999)], 12–17 years [1391 (436–2842) vs. 4569 (800.5–10000)] and ≥18 years [1340 (229–4360) vs. 3722 (555–10000)]. Dupilumab treatment reduced total serum IgE levels in patients aged 6 months and older with moderate-to-severe AD. Overall safety was consistent with the known dupilumab safety profile.

A CCR4 antagonist attenuates atopic dermatitis-like skin inflammation by inhibiting the recruitment and expansion of Th2 cells and Th17 cells.

CCR4 is a major trafficking receptor for T-helper (Th) 2 cells and Th17 cells and is considered as a potential therapeutic target for atopic dermatitis (AD). The CCR4 ligands CCL17 and CCL22 have been reported to be upregulated in the skin lesions of AD patients. Of note, thymic stromal lymphopoietin (TSLP), a master regulator of the Th2 immune response, promotes the expression of CCL17 and CCL22 in AD skin lesions. Here, we investigated the role of CCR4 in an AD mouse model induced by MC903, a TSLP inducer. Topical application of MC903 to ear skin increased the expression of not only TSLP but also CCL17, CCL22, the Th2 cytokine IL-4, and the Th17 cytokine IL-17A. Consistently, MC903 induced AD-like skin lesions as shown by increased epidermal thickness; increased infiltration of eosinophils, mast cells, type 2 innate lymphoid cells, Th2 cells, and Th17 cells; and elevated serum levels of total IgE. We also found increased expansion of Th2 cells and Th17 cells in the regional lymph nodes (LNs) of AD mice. Compound 22, a CCR4 inhibitor, ameliorated AD-like skin lesions with reduction of Th2 cells and Th17 cells in the skin lesions and regional LNs. We further confirmed that compound 22 diminished the expansion of Th2 cells and Th17 cells in the coculture of CD11c+ dendritic cells (DCs) and CD4+ T cells derived from the regional LNs of AD mice. Collectively, CCR4 antagonists may exhibit anti-allergic effects by inhibiting both the recruitment and expansion of Th2 cells and Th17 cells in AD.

CORRELATION BETWEEN TOTAL SERUM IgE LEVELS AND SOME CHARACTERISTICS IN VIETNAMESE PEMPHIGOID PATIENTS

Objectives: To determine the correlation between total serum IgE levels and some clinical and subclinical characteristics in pemphigoid patients.Methods: A cross-sectional study on 42 pemphigoid patients, all of which were newly diagnosed. Information was collected from patient interviews and medical records. Total serum IgE levels were determined using a total IgE ELISA following the manufacturer’s instructions. Eosinophil counts were analyzed on the same day when serum samples were taken. For IgE DIF staining of perilesional skin, IgE Goat anti-Human, FITC was used, incubation was performed overnight at 4oC.Results: Among 42 pemphigoid patients, the average age was 73.2 ± 15.5 years old. 60% of pemphigoid patients had elevated total serum IgE levels, the mean value was 121.6 ± 101.8 UI/mL. Total serum IgE levels were significantly correlated with eosinophil counts (r = 0.61; p < 0.05) and the BPDAI urticaria/erythema (U/E) score (r = 0.50; p < 0.05). However, total circulating IgE levels were not significantly associated with total BPDAI score (p > 0.05). DIF IgE staining on perilesional skin of pemphigoid patients had a positive rate of 14.3%.Conclusion: Total serum IgE values correlated with some clinical and subclinical characteristics in pemphigoid patients. IgE autoantibodies were present in the skin of pemphigoid patients, supporting the hypothesis that IgE potentially modulates pruritus associated with pemphigoid.

The Very Low IgE Producer: Allergology, Genetics, Immunodeficiencies, and Oncology.

Opposite to other immunoglobulin (Ig) classes and subclasses, there is no consensus on the definition of normal levels of serum total IgE. However, longitudinal studies on birth cohorts produced growth charts of total IgE levels in helminth-free and never atopic children and defining the normal ranges of total serum IgE concentration at the individual, rather than population, level. Accordingly, very 'low IgE producers' (i.e., children whose tIgE level belong to the lowest percentiles) became atopic while keeping their total IgE levels in a range considered 'normal' if compared to the general age-matched population but 'abnormally high' if projected on the tIgE growth chart against the trajectory of that child's own percentile levels. In 'low IgE producers', the IgE-specific activity, i.e., the ratio between allergen-specific and total IgE, is more important than the absolute specific IgE levels to confirm causality between allergen exposure and allergic symptoms. Patients with allergic rhinitis or peanut anaphylaxis but low or undetectable allergen-specific IgE levels must therefore be reconsidered considering their total IgE levels. Low IgE producers have been also associated with common variable immunodeficiency, lung diseases, and malignancies. A few epidemiological studies have shown a higher risk of malignancies in very low IgE producers, leading to a debated hypothesis proposing a novel, evolutionistic-relevant function for IgE antibodies for antitumor immune surveillance.

Association of Maternal Asthma and Total Serum Immunoglobulin E levels with Obstetric Complications: The Japan Environment and Children's Study.

To evaluate the association between maternal asthma (MA) and obstetric complications, while considering subdivided total serum immunoglobulin E (IgE) levels. Data of the participants enrolled in the Japan Environment and Children's Study between 2011 and 2014 were analyzed. In total, 77,131 women with singleton live births at and after 22weeks of gestation were included. MA was defined based on a self-administered questionnaire. Women with MA were stratified based on the quartile of total serum IgE levels during pregnancy as follows: low IgE levels (< 52.40IU/mL), moderate IgE levels (52.40-331.00IU/mL), and high IgE levels (> 331.00IU/mL). The adjusted odds ratios (aORs) for preterm births (PTB), small for gestational age (SGA) infants, gestational diabetes mellitus, and hypertensive disorders of pregnancy (HDP) were calculated using multivariable logistic regression, while considering women without MA as reference and maternal socioeconomic factors as confounders. The aORs for SGA infants and HDP in women with MA and high total serum IgE levels were 1.26 (95% confidence interval [CI], 1.05-1.50) and 1.33 (95% CI, 1.06-1.66), respectively. The aOR for SGA infants among women with MA and moderate total serum IgE levels was 0.85 (95% CI, 0.73-0.99). The aOR for PTB among women with MA and low total serum IgE levels was 1.26 (95% CI, 1.04-1.52). MA with subdivided total serum IgE levels was associated with obstetric complications. Total serum IgE level may be a potential prognostic marker to predict obstetric complications in pregnancies with MA.

The G allele of the ADAM33 T1 polymorphism (rs2280091) is a risk factor associated with asthma severity among the Iraqi Arab population

BackgroundThe gene encoding a disintegrin and metalloproteinase domain 33 (ADAM33) is known to be associated with asthma in different ethnic groups. In Iraq, among the Arab ethnic background, this association has not yet been highlighted. MethodsOne hundred and ninety-two asthmatics were examined; 118 males and 74 females (mean age 38.23 ± 9.13 years). The control group was 183; 110 males and the rest were females. The SNP of rs2280091 A/G (T1) was studied here to determine adam33 genotyping status using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). The level of total IgE was measured using enzyme-linked immunosorbent assay (ELISA). ResultsSignificant differences (p = 0.004) in the frequencies of the ADAM33 mutant allele carriers between patients and controls were found OR = 1.62 (95% CI 1.16–2.27). This association was significant in individuals who carried homozygous (GG) or heterozygous (AG) variant type genotypes in a reference with carriers of wild-type (AA) genotypes. The odds ratios were 1.70 (95% CI 1.11–2.60, p = 0.013), 2.97 (95% CI 1.00–8.75, p = 0.047), 1.79 (95% CI 1.18–2.71 p = 0.005) for those who carried (wt/vt), (vt/vt), and (wt/vt + vt/vt), respectively. Correlation based on gender shows the presence of a significant association (p = 0.01a) for female mutant allele carriers OR = 1.96 (95% CI 1.15–3.36), but not in the case of male. Significant difference (p = 0.02) in the frequencies of mutant G allele carrier compared to wild A allele carrier was also found correlated in patients with severe asthma than moderate or mild asthma, OR = 1.78 (95% CI 1.10–2.89). Serum total IgE level in patients with GG genotype (219.37 ± 108.49) was significantly higher than in patients with AG and AA genotypes, respectively (193.22 ± 85.83), (157.11 ± 92.10), (P = 0.001). ConclusionsCarries of GG and AG alleles T1 ADAM33 polymorphism are at a high risk of developing functional susceptibility of asthma.

Therapeutic efficacy and mechanism of a solubilized Sturgeon oil in a mouse model of house dust mite-induced atopic dermatitis

Abstract The therapeutic effect and action mechanism of solubilized Sturgeon oil (SSO) against atopic dermatitis (AD) were examined in NC/Nga mice. SSO was prepared from the fish oil obtained from Sturgeons using physical solubilization processes. AD was induced by topical application of house dust mite (HDM) extract on the dorsal skin of NC/Nga mice, and then treated with SSO. SSO exerted potent therapeutic activity on AD symptoms. Histological analysis revealed that SSO reduced epidermal hyperplasia and suppressed infiltration of mast cells and eosinophils in the dorsal skin. In addition, SSO significantly reduced the serum total IgE and HDM-specific IgE levels in AD-induced NC/Nga mice. Analysis of the dorsal skin tissues showed that SSO significantly downregulated the expression levels of IL-4, 5, 13, 17A and COX-2, while upregulated the expression levels of IL-10 and filaggrin. In vitro studies also showed that SSO suppressed the production of Th2 cytokines including IL-4, 5 and 13, while increasing the production of IL-10, from anti-CD3/CD28-stimulated Th2 cells. These results show that SSO exerts therapeutic effect on AD in NC/Nga mice through Th2-related immunomodulatory activities.

Analysis of intronic SNP (rs4147358) and expression of SMAD3 gene in Atopic Dermatitis: A case-control study

BackgroundAtopic Dermatitis (AD) is a multifactorial cutaneous disorder associated with chronic inflammation of the skin. Growing evidence points to TGF-β/SMAD signaling as a key player in mediating inflammation and the subsequent tissue remodeling, often resulting in fibrosis. This study investigates the role of a core transcription factor involved in TGF-β signaling i.e., SMAD3 genetic variants (rs4147358) in AD predisposition and its association with SMAD3 mRNA expression, serum IgE levels, and sensitization to various allergens in AD patients. MethodsA total of 246 subjects including 134 AD cases and 112 matched healthy controls were genotyped for SMAD3 intronic SNP by PCR-RFLP. mRNA expression of SMAD3 was determined by quantitative Real-Time PCR (qRT-PCR), Vitamin-D levels by chemiluminescence, and total serum IgE levels by ELISA. In-vivo allergy testing was performed for the evaluation of allergic reactions to house dust mites (HDM) and food allergens. ResultsA significantly higher frequency of mutant genotype AA (cases: 19.4% vs controls: 8.9%) (OR = 2.8, CI = 1.2 – 6.7, p = 0.01) was observed in AD cases. The mutant allele ‘A’ also showed a 1.9-fold higher risk for AD compared to the wild allele ‘C’ indicating that the carriers of the A allele have a higher risk for AD predisposition (OR-1.9, CI = 1.3–2.8, p < 0.001). In addition, quantitative analysis of SMAD3 mRNA in peripheral blood showed 2.8-fold increased expression in AD cases as compared to healthy controls. Stratification analysis revealed the association of the mutant AA genotype with deficient serum Vitamin D levels (p = 0.02) and SMAD3 mRNA overexpression with HDM sensitization (p = 0.03). Furthermore, no significant association of genotypes with SMAD3 mRNA expression was observed. ConclusionOur study indicates that SMAD3 intronic SNP bears a significant risk of AD development. Moreover, overexpression of SMAD3 mRNA and its association with HDM sensitization highlights the possible role of this gene in AD pathogenesis.

461 Total serum IgE levels as a predictor for clinical response to omalizumab in patients with chronic spontaneous urticaria: A systematic review and meta-analysis

461 Total serum IgE levels as a predictor for clinical response to omalizumab in patients with chronic spontaneous urticaria: A systematic review and meta-analysis

Gene variants and mRNA expression analysis of SOCS3 and its association with serum IL-4 levels in atopic diseases

BackgroundThe suppressors of cytokine signaling (SOCS) are a class of negative regulators for several aspects of cytokine signaling that have been attributed to the pathophysiology of inflammatory disorders. Given the role of the SOCS3 gene in regulating Th2 cell proliferation, our study aimed to analyze two SOCS3 SNPs viz. rs8074003 and rs7222391, and their potential influence on IL-4 levels and SOCS3 mRNA expression besides analyzing the interaction of the SOCS3 genotypes with the various clinicopathological parameters. MethodsA total of 314 subjects including 154 atopic cases and 160 healthy controls were genotyped for SOCS3 polymorphisms by PCR-RFLP. SOCS3 mRNA was quantified by Real-Time PCR. The serum IL-4 and total IgE levels were determined by ELISA and Vitamin-D levels were quantified by chemiluminescence. ResultsThe CC genotype of rs8074003 was more frequent in atopic cases and posed a 3- fold risk of atopy (p = 0.001) whereas CG and GG genotypes were widespread in the controls (p = 0.1). For the other SNP rs7222391, there was no difference in genotypic and allelic distribution. The SOCS3 mRNA expression and serum IL-4 levels were substantially increased in the atopic cases with a significant positive correlation between them (p < 0.05). ConclusionSOCS3 SNP rs8074003 poses a convincing risk of atopic disease development. The SOCS3 expression and IL-4 levels were up-regulated in total atopy and in its different presentations. It seems plausible to target SOCS3 and IL-4 as a potential target for the diagnosis of atopy and for the development of reliable personalized therapeutic strategies to control atopic conditions.

Real-world efficacy of anti-IL-5 treatment in patients with allergic bronchopulmonary aspergillosis

Despite standard treatment with systemic corticosteroids and/or antifungal triazoles, a substantial proportion of patients with allergic bronchopulmonary aspergillosis (ABPA) experience frequent relapses and require long-term treatment despite unfavorable adverse effects. We investigated the efficacy and safety of anti-interleukin (IL)-5/IL-5 receptor α chain (Rα) monoclonal antibodies (mAbs) in patients with ABPA complicated by asthma. ABPA cases treated with anti-IL-5/IL-5Rα mAbs were collected from 132 medical institutes in 2018 and published case reports in Japan. Clinical outcomes, laboratory and physiological data, and radiographic findings during 32 weeks before and after treatment were retrospectively evaluated. We analyzed 29 cases of ABPA: 20 treated with mepolizumab and nine with benralizumab. Treatment with anti-IL-5/IL-5Rα mAbs reduced the frequency of exacerbations (p = 0.03), decreased the dose of oral corticosteroids (p < 0.01), and improved pulmonary function (p = 0.01). Mucus plugs in the bronchi shrank or diminished in 18 patients (82%). Despite the clinical/radiographical improvement, serum levels of total IgE, the key biomarker for the pharmacological response in ABPA, were unchanged. Anti-IL-5/IL-5Rα mAbs that directly target eosinophils are promising candidates for the treatment of patients with ABPA, especially those with mucus plugs in the bronchi.

Effect of Calycosin on Airway Inflammation and Airway Remodeling in Allergic Asthma Mouse Model

Background: This study aimed to construct a TDI-induced mouse model of asthma, and evaluate the potential effects and possible molecular mechanisms of Calycosin on airway inflammation and airway remodeling in mouse model. Material and methods: ELISA method was applied to detect the total serum IgE level and the inflammatory cytokine level in the bronchoalveolar lavage fluid. The total number of cells and the proportion of inflammatory cells in BALF were evaluated under an optical microscope. HE was employed to assess and score the infiltration of peritracheal and perivascular inflammatory cells in lung tissue, and PAS staining was used to assess the proportion of goblet cells in the airway epithelium and the thickness of airway epithelial reticular basement membrane in each group of mice. WB was used to detect the expressions of HMGB1 and a-SMA in cells. Immunofluorescence staining was used to detect the expressions of HMGB1 and a-SMA in 16HBEs. Results: The airway hyperresponsiveness of the Calycosin TDI asthma mice decreased, the inflammatory factors in BALF and the total serum IgE levels decreased, the airway epithelial goblet cell metaplasia and the thickness of the airway epithelial reticular basement membrane were improved, thus reducing the up-regulation of HMGB1 and a-SMA expression of 16HBES induced by TDI-HSA. Conclusion: In our study, in the TDI-induced mouse model of asthma, the administration of drug to inhibit the activation of AKT can reduce airway inflammation and airway remodeling. These findings have enriched the current understanding of Calycosin and provided a basis for future research. However, there are also some limitations: How does TDI activate the AKT signaling pathway? After the activation of the AKT pathway, the mechanism by which the expressions of HMGB1, α-SMA and Collagen-I were up-regulated has not been fully elucidated.

Investigations of a combination of atopic status and age of asthma onset identify asthma subphenotypes

Objective Subphenotypes of asthma may be determined by age onset and atopic status. We sought to characterize early or late onset atopic asthma with fungal or non-fungal sensitization (AAFS or AANFS) and non-atopic asthma (NAA) in children and adults in the Severe Asthma Research Program (SARP). SARP is an ongoing project involving well-phenotyped patients with mild to severe asthma. Methods Phenotypic comparisons were performed using Kruskal-Wallis or chi-square test. Genetic association analyses were performed using logistic or linear regression. Results Airway hyper-responsiveness, total serum IgE levels, and T2 biomarkers showed an increasing trend from NAA to AANFS and then to AAFS. Children and adults with early onset asthma had greater % of AAFS than adults with late onset asthma (46% and 40% vs. 32%; P < 0.00001). In children, AAFS and AANFS had lower % predicted FEV1 (86% and 91% vs. 97%) and greater % of patients with severe asthma than NAA (61% and 59% vs. 43%). In adults with early or late onset asthma, NAA had greater % of patients with severe asthma than AANFS and AAFS (61% vs. 40% and 37% or 56% vs. 44% and 49%). The G allele of rs2872507 in GSDMB had higher frequency in AAFS than AANFS and NAA (0.63 vs. 0.55 and 0.55), and associated with earlier age onset and asthma severity. Conclusions Early or late onset AAFS, AANFS, and NAA have shared and distinct phenotypic characteristics in children and adults. AAFS is a complex disorder involving genetic susceptibility and environmental factors.

Topical Administration of Gardenia jasminoides Extract Regulates Th2 Immunity in OVA-Induced Mice.

A key feature of an allergic immune response is a T helper type 2 (Th2)-mediated response with production of allergen-specific IgE antibodies. Gardenia jasminoides extract with the crocin removed (GJExCR) has been shown to inhibit IgE-mediated allergic disease. To evaluate the efficacy and mechanism-of-action of this inhibition, GJExCR was used in an ovalbumin (OVA)-induced allergy model in BALB/C mice. Sensitization of BALB/C mice with OVA and aluminum hydroxide was performed on days 1 and 14 by intraperitoneal injection, followed by OVA challenge to the dorsal skin for 2 weeks before removal. Seven days post-challenge, mice were treated with GJExCR topically every day for 11 days. Enzyme-linked immunosorbent assay, flow cytometry analysis, real-time PCR, and western blot were performed to determine IgE and Th2 cytokine levels. Following OVA challenge, Th2 cytokine expression and both total and OVA-specific serum IgE levels increased, of which OVA-specific IgE and Th2 cytokine levels decreased after GJExCR treatment. Flow cytometry analysis revealed that GJExCR treatment decreased CD4+ and CD8+ T cell populations in the spleen and lymph nodes. In addition, treatment with GJExCR downregulated signal transducer and activator of transcription 1 (STAT1) activation and Th2 cytokine levels as compared to control. GJExCR containing geniposide downregulated STAT1 activation in HaCaT cells. These findings demonstrate that GJExCR exerts its anti-allergy effect via inhibition of STAT1 activation, thus regulating the immune response via modulation of Th2 cytokine release and IgE levels. Therefore, we propose GJExCR as a potential treatment for allergic hypersensitivity reactions.

Dupilumab Efficacy in Patients with Uncontrolled Moderate-to-Severe Type 2 Asthma Regardless of Perennial Aeroallergen Sensitization.

Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukins-4/-13, key and central drivers of type 2 (T2) inflammation in multiple diseases. In phase 3 QUEST (NCT02414854), dupilumab vs placebo significantly reduced asthma exacerbation rates (AER) and improved pre-bronchodilator forced expiratory volume in 1 second (FEV1) in patients with uncontrolled, moderate-to-severe asthma, with greater effects in patients with elevated T2 biomarkers (≥150 eosinophils/µL or fractional exhaled nitric oxide [FeNO] ≥25 parts per billion). Overall safety was consistent with the known dupilumab safety profile. This post hoc analysis assessed dupilumab efficacy in QUEST patients with T2 asthma with evidence of an allergic phenotype (baseline serum IgE ≥30 IU/mL and aeroallergen-specific IgE ≥0.35 IU/mL) by number of aeroallergen sensitizations: 1, 2, 3, or ≥4. Non-sensitized patients (serum total IgE <30 IU/mL without evidence of allergic phenotype) were also assessed. Endpoints were annualized AER, change from baseline in pre-bronchodilator FEV1 and asthma control (5-item Asthma Control Questionnaire [ACQ-5]), and FeNO and serum total IgE levels over the 52-week treatment period. In all subgroups by number of allergens sensitized, dupilumab vs placebo reduced AER by 35-67% and improved both pre-bronchodilator FEV1 at Week 12 (least squares mean differences: 0.10-0.26 L across subgroups) and ACQ-5 score at Week52 (-0.26 to -0.43). Dupilumab significantly reduced FeNO and total IgE levels at Week 52 compared with placebo. Similar results were observed in non-sensitized patients. Dupilumab improved clinical outcomes and reduced biomarker levels in patients with uncontrolled, moderate-to-severe T2 asthma irrespective of allergen sensitization status or number. ClinicalTrials.gov Identifier: NCT02414854.

Dupilumab for chronic rhinosinusitis with nasal polyps: real-life retrospective 12-month effectiveness data.

Dupilumab, an IL-4/13 receptor inhibitor, is approved for the treatment of uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). We evaluated the effectiveness and safety of dupilumab for CRSwNP based on retrospective 12-month follow-up data of 41 patients. We analysed nasal endoscopy scores, patient-reported outcome measures (PROMs), 12-item SniffinSticks odor identification test (SSIT-12), total serum IgE, serum Eosinophilic Cationic Protein (ECP), and total blood eosinophil count (BEC). We performed statistical analysis using non-parametric ANOVA-type models and Spearman's correlation. At month 1, endoscopy scores, PROMs and SSIT-12 showed meaningful improvements that were maintained until month 12. Initial elevations in both median ECP and BECs returned to near baseline levels by month 12. The percentage of patients withBEC ≤ 0.6 remained increased at month 12 (42.1%) compared to baseline (19.5%). Total serum IgE levels decreased progressively and correlated with nasal polyp scores at month 12. "Adequate response" was reached in 86.8% of our cohort. Our data suggest that dupilumab is effective for the treatment of CRSwNP. The potential for short- and long-term BEC elevations in some CRSwNP patients should be carefully monitored.