Serum IgE Levels Research Articles

Anti-allergic effect of vitamin C through inhibiting degranulation and regulating TH1/TH2 cell polarization.

Food allergy has become a global public health problem. This study aimed to explore the possible anti-allergic effect of vitamin C (VC). A rat basophilic leukemia (RBL)-2H3 cell degranulation model was used to assess the effect of VC on degranulation in vitro, and an ovalbumin (OVA)-induced BALB/c mouse allergy model was used to assess the anti-allergy effect of VC in vivo. In vitro, VC significantly attenuated the release of β-hexosaminidase, tryptase and histamine, and also reduced cytokine production (interleukins 4 and 6, tumor necrosis factor α) significantly (P < 0.05), with the inhibitory effect demonstrating a positive correlation with VC dose. In vivo, compared with the OVA group, the levels of serum immunoglobulins E and G1 of the VC low-dose (VCL) group (50 mg kg-1) and high-dose (VCH) group (200 mg·kg-1) were significantly reduced (P < 0.05). Furthermore, the plasma histamine level was also significantly decreased (P < 0.05). Moreover, TH2 cell polarization in mice of the VCL and VCH groups was significantly inhibited (P < 0.05), promoting the TH1/TH2 cell polarization balance. Additionally, VC treatment enhanced the expression of CD80 (P < 0.05) in spleen and small intestine tissues, while significantly inhibiting the expression of CD86 (P < 0.05); notably, high-dose VC treatment was more effective. VC exerted an anti-allergic effect through inhibiting degranulation and regulating TH1/TH2 cell polarization balance. © 2024 Society of Chemical Industry.

Therapeutic and immune-regulation effects of Scutellaria baicalensis Georgi polysaccharide on pseudorabies in piglets.

Pseudorabies virus (PRV) can cause fatal encephalitis in newborn pigs and escape the immune system. While there is currently no effective treatment for PRV, Scutellaria baicalensis Georgi polysaccharides (SGP) and Rodgersia sambucifolia Hemsl flavonoids (RHF) are traditional Chinese herbal medicines with potential preventive and therapeutic effects against PRV infection. In order to explore which one is more effective in the prevention and treatment of PRV infection in piglets. We investigate the therapeutic effects of RHF and SGP in PRV-infected piglets using clinical symptom and pathological injury scoring systems. The immune regulatory effects of RHF and SGP on T lymphocyte transformation rate, cytokines, T cells, and Toll-like receptors were also measured to examine the molecular mechanisms of these effects. The results showed that SGP significantly reduced clinical symptoms and pathological damage in the lungs, liver, spleen, and kidneys in PRV-infected piglets and the T lymphocyte conversion rate in the SGP group was significantly higher than that in the other treatment groups, this potential dose-dependent effect of SGP on T lymphocyte conversation. Serum immunoglobulin and cytokine levels in the SGP group fluctuated during the treatment period, with SGP treatment showing better therapeutic and immunomodulatory effects in PRV-infected piglets than RHF or the combined SGP + RHF treatment. In conclusion, RHF and SGP treatments alleviate the clinical symptoms of PRV infection in piglets, and the immunomodulatory effect of SGP treatment was better than that of the RHF and a combination of both treatments. This study provides evidence for SGP in controlling PRV infection in piglets.

Serum Immunoglobulin E Level and Its Relationship with Eosinophil Count among Patients with Allergic Rhinitis in Tertiary Hospital in Bauchi, Northeastern Nigeria: A Cross-Sectional Study.

Allergic rhinitis is an immunoglobulin E-mediated hypersensitivity disease of the mucous membrane of the nasal airway. There is a paucity of information regarding serum immunoglobulin E level and its relationship with eosinophil count among patients with allergic rhinitis in our facility and Northeastern Nigeria. To determine serum immunoglobulin E level and its relationship with eosinophil count among patients with allergic rhinitis. It was a cross-sectional study of consecutive patients diagnosed with allergic rhinitis that were recruited from the ear, nose, and throat surgery and respiratory medicine clinics of ATBUTH, Bauchi, Bauchi State, Northeastern Nigeria, from January 01, 2022, to May 31, 2023. Five milliliters of blood were analyzed for immunoglobulin E estimation using an immunoglobulin E ELISA kit and determination of eosinophil count using pack five hematologic autoanalyzer. Extracted data were analyzed using IBM SPSS version 23.0 software. There were 61 patients studied comprising 22 (36.1%) males and 39 (63.9%) females with a male-to-female ratio of 1:1.7. Their ages range from 18 to 77 years old. The mean age, serum IgE level, and eosinophil counts of all three patients were 38.65 ± 14.34 years, 371.24 ± 82.63 IU/ml, and 3.35 ± 2.87%, respectively. All (100%) participants had raised serum IgE levels, and 88.5% had normal eosinophil count. There was no significant correlation between the serum IgE level and eosinophil counts (r = -0.206; P = 0.112). All of the participants had a high serum IgE level. There was no significant association between serum IgE and eosinophil count.

The role of matrix metalloproteinase-2 and miR-196a2 in bronchial asthma pathogenesis and diagnosis

BackgroundBronchial asthma is a persistent inflammatory respiratory condition that restricts the passage of air and causes hyperresponsiveness. Chronic asthma can be classified into three categories: mild, moderate, and severe. Remodeling took place as the extracellular matrix accumulated in the walls of the airways. Inflammation occurs as a result of the damage caused by matrix metalloproteinase-2 (MMP-2) to basement membrane type IV collagen. The severity of asthma may be associated with miR-196a2. The objective of our study was to investigate the underlying mechanisms and clinical relevance of miR-196a2 and MMP-2 serum levels in relation to the severity of asthma. MethodsThis study recruited 85 controls and 95 asthmatics classified as mild, moderate, or severe. Expression of miR-196a2 was measured by quantitative reverse transcriptase PCR. Using the enzyme-linked immunosorbent assay (ELISA), MMP-2, IL-6, and total immunoglobulin E (IgE) levels in the serum of asthmatics of various grades were compared to a control group. MMP-2's diagnostic and prognostic potential was determined using ROC curve analysis. This study also measured blood Eosinophils and PFTs. We examined MMP-2's connections with IgE, blood Eosinophils, and PFTs. ResultsThe current investigation found that miR-196a2 expression was significantly higher in the control group than in asthmatic patients as a whole. The study found that severe asthmatics had higher MMP-2, IL-6, and IgE serum levels than healthy controls. We identified the MMP-2 serum concentration cutoff with great sensitivity and specificity. Significant relationships between MMP-2 serum level and miR-196a2 expression in the patient group with severe asthmatics were found. The MMP-2, IL-6, and IgE serum levels were considerably higher in mild, moderate, and severe asthmatics than controls. The miR-196a2 expression and MMP-2 serum concentration correlated positively with IgE and blood eosinophils % and negatively with all lung function tests in the asthmatic patient group.Conclusion: the study revealed that the elevated miR-196a2 expression and serum concentration of MMP-2, IL-6, and IgE associated with elevated blood eosinophils % is associated with pathophysiology and degree of asthma severity. The miR-196a2 expression and MMP-2 serum concentration have a promising diagnostic and prognostic ability in bronchial asthma.

The Effects of Budesonide Inhalation Treatment on the Expression Levels of Serum IL-6, TGF-β1, and IgE and Pulmonary Function in Patients with Cough Variant Asthma and an Evaluation of Treatment Efficacy.

To retrospectively study the effects of budesonide inhalation combined with conventional symptomatic treatment on serum inflammatory factor expression levels and pulmonary function in patients with cough variant asthma (CVA) and to evaluate treatment efficacy. This retrospective cohort study included 200 patients diagnosed with CVA at the Second Hospital of Jiaxing between January 2022 and June 2023 and given conventional symptomatic treatment plus budesonide inhalation were included in this study. Patients were divided into a no remission group, a partial remission group and a complete remission group based on treatment effect. The expression levels of serum inflammatory factors, cough symptom scores, and small airway function indicators in the three groups of patients at different time points were compared. In the three groups of CVA patients, after receiving budesonide inhalation combined with conventional symptomatic treatment, the expression levels of serum IL-5, IL-6, IL-8, TNF-α, TGF-β1, and IgE and number of eosinophils significantly decreased (P <0.05). There were statistically significant differences in the IL-6 and TGF-β1 levels among the three groups of CVA patients at T1, T2 and T3. There were statistically significant differences in IgE levels, number of eosinophils, cough symptom scores, and small airway function indicators between T2 and T3 (P<0.05). The receiveroperatingcharacteristic (ROC) curve prediction analysis revealed significant differences in the expression of IL-6 and TGF-β1 at T1, T2, and T3. Budesonide inhalation combined with conventional symptomatic treatment can significantly reduce the levels of serum inflammatory factors in patients with CVA to reduce inflammation and the allergic response, thereby reducing the cough symptom score, improving pulmonary function, and improving therapeutic efficacy. In addition, IL-6 and TGF-β1 can be used as early predictors of budesonide inhalation efficacy.

Monotropein Alleviates Ovalbumin-Induced Asthma in Mouse Model by Inhibiting AKT/NF-κB Pathway

Introduction: Clinical management of asthma remains as a prevalent challenge. Monotropein (MON) is a naturally occurring cyclic enol ether terpene glycoside with medical application potential. This study aims to evaluate the potential therapeutic effects of MON in the mouse model of chronic asthma. Methods: An ovalbumin (OVA)-induced asthmatic mouse model was established to evaluate the therapeutic effect of MON at different doses (20, 40, and 80 mg/kg). The potential involvement of protein kinase B (AKT)/nuclear factor kappa B (NF-κB) pathway in the effect of MON was investigated by the administration of an AKT activator SC79. Histological changes in pulmonary tissues were examined by hematoxylin and eosin staining. The profiles of inflammatory cytokines (interleukin [IL]-4, IL-5, IL-13, and tumor necrosis factor [TNF]-α) in bronchoalveolar lavage fluid (BALF), and OVA-specific IgE in blood samples were analyzed by enzyme-linked immunosorbent assay (ELISA). The oxidative stress in the lung tissues was determined by measuring malondialdehyde level. The phosphorylation activation of AKT and NF-κB was examined by immunoblotting in the lung tissues. Results: MON treatment suppressed the infiltration of inflammatory cells in the airways of OVA-induced asthma mice and reduced the thickness of the bronchial wall and smooth muscle layer in a dose-dependent manner. MON treatment also reduced the levels of OVA-specific IgE in serum and cytokines in BALF in asthma-induced mice, and attenuated the oxidative stress in the lung tissues. OVA induced the phosphorylation of AKT and NF-κB proteins in the lung tissues of asthmatic mice, which was significantly suppressed by MON treatment. The co-administration of AKT activator SC79 impaired the therapeutic effect of MON on asthma-induced mice. Conclusion: Our data demonstrated the potential therapeutic effect of MON on asthmatic mouse model, suggesting that MON attenuated the inflammatory and oxidative damages in ling tissues by dampening the AKT/NF-κB signaling pathway.

Bergapten inhibits airway inflammation and MRGPRX2-mediated mast cells activation by targeting NR4A1

Asthma is a serious global health problem affecting 300 million persons around the world. Mast cells (MCs) play a major role in airway hyperresponsiveness (AHR) and inflammation in asthma, their exact effector mechanisms remain unclear. Here, we aim to investigate the inhibitory effect of Bergapten (BER) on MRGPRX2-mediated MCs activation through asthma model.Mouse model of asthma was established to examine the anti-asthmatic effects of BER. Calcium (Ca2+) influx, β-hexosaminidase and histamine release were used to assess MCs degranulation in vitro. RNA-Seq technique was conducted to study the gene expression profile. RT-PCR and Western Blotting were performed to examine targeting molecules expression. BER inhibited AHR, inflammation, mucous secretion, collagen deposition and lung MCs activation in asthma model. BER dramatically reduced levels of IL4, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF), as well as inflammatory cells. BER also reduced serum IgE levels. Pretreatment MCs with BER inhibited substance P (SP)-induced Ca2+ influx, degranulation and cytokines release from MCs. BER also reduced the phosphorylation levels of PKC, PLC, IP3R, AKT and ERK, which were induced by SP. Furthermore, RNA-seq analysis showed that SP up-regulated 68 genes in MCs, while were reversed by BER. Among these 68 genes, SP up-regulated NR4A1 expression, and this effect was inhibited by BER. Meanwhile, knockdown of NR4A1 significantly attenuated SP-induced MCs degranulation. In conclusion, NR4A1 plays a major role in MRGPRX2-mediated MCs activation, BER inhibited AHR and inflammation in asthmatic model by inhibiting MCs activation through MRGPRX2-NR4A1 pathway.

Research Note: Effects of the intermittent feeding of microencapsulation essential oil on laying performance, egg quality, immune response, intestinal morphology, and oxidation status of laying hens

The aim of this study was to evaluate the effect of microencapsulated essential oils (MEO) on the laying performance, egg quality, immunity, intestinal morphology, and oxidative status of laying hens. A total of 640 Hy-line Brown laying hens, 41 weeks of age, were randomly divided into four groups, each with 8 replicates containing 20 birds per replicate. The dietary conditions tested included a basal diet (Control) or the basal diet supplemented with various levels of MEO at 100 mg/kg (MEO100), 300 mg/kg (MEO300), and 500 mg/kg (MEO500). The three treatment groups were intermittently fed MEO, following an alternating schedule of 1 week on and 1 week off for a total of 56 days. Results showed that feeding MEO at levels of 300 and 500 mg/kg improved both egg production and feed conversion ratios compared to the control group. Hens consumed MEO-supplemented diets exhibited a significant decrease in the breaking egg ratio (P<0.05) compared to those fed the control diet. Shell thickness and Haugh unit values significantly increased in the groups receiving 300 and 500 mg/kg of MEO (P<0.05). Both the MEO300 and MEO500 treatments led to improvements in immunoglobulin (IgA, IgM, and IgG) and cytokine (IL-2 and IFN-γ) levels in serum. Hens in the MEO300 and MEO500 groups exhibited higher values for parameters related to intestinal morphometry compared to the control group. Furthermore, supplementation with 300 and 500 mg/kg of MEO enhanced the antioxidant capacity of plasma, as evidenced by increased activities of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), and catalase (CAT) (P<0.05). In summary, the intermittent feeding of MEO improved egg production, enhanced antioxidative processes, immune functions, and intestinal morphology, leading to an amelioration in the egg quality of laying hens. Our data demonstrate that supplementation of 300 mg/kg of MEO in feed can significantly improve animal health and egg quality. Implementation of these feeding practices could have a positive economic impact on poultry and egg industry.

The Therapeutic Potential of Copper Peptides on Atopic Dermatitis Lesions in BALB/c mice and Human Keratinocytes

PURPOSE: Atopic dermatitis (AD), often referred to as eczema, is a chronic disease characterized by skin inflammation, itchiness, irritation, and dryness. It is caused mainly by immune dysregulation. Copper peptides (CP) have been used for a variety of skin-related purposes. In this study, we examined the effect of CP on AD induced in BALB/c mice.METHODS: BALB/c mice were separated into the following five groups: control, AD-only, AD+CP10, AD+CP100, and AD+CERA. AD was induced using house dust mite (HDM) extract and 2,4-dinitrochlorobenzene (DNCB). The mice received CP or ceramide (CERA; positive control) based on their group allocation. Histopathological analysis was performed to assess the effect of CP on mast cell infiltration. Dermal and epidermal thickness were measured using microphotographs of hematoxylin-and-eosin-stained tissue. We examined the serum immunoglobulin E (IgE) levels and mRNA gene expression of pathogenic cytokines in the mouse ear tissue and in human keratinocytes.RESULTS: CP treatment decreased dermal and epidermal mouse ear thickness and mast cell infiltration in the ear tissue in a dosedependent manner. It also decreased the serum IgE levels and the mRNA gene expression of pathogenic cytokines in the ear tissue and in the human keratinocytes. Interestingly, the therapeutic effect of CP was more robust than that of CERA.CONCLUSIONS: These results indicate that CP may have therapeutic potential against AD.

Allergic bronchopullmonary aspergillosis (ABPA) - an Update

Allergic bronchopulmonary aspergillosis (ABPA) is a regular occurrence in everyday pneumology. ABPA should be considered in patients with severe asthma, in mould allergic patients with very high serum IgE levels and in patients with cystic fibrosis. The aim should be to make the diagnosis as early as possible in the course of the disease to avoid late complications such as bronchiectasis and fibrotic lung remodelling. Symptoms are highly variable and rather non-specific, overlapping with those of the underlying primary disease. However, clearly defined diagnostic criteria exist, so that the diagnosis can be made relatively easily if one thinks of it. In therapy, systemic steroids and antifungals (mainly azoles) play the leading role. However, biologics have been gaining in importance in recent years, especially in cases of insufficient therapy response or occurrence of side effects to standard therapies, as well as an alternative in permanently steroid-dependent patients.

Unraveling the Role of RNase L Knockout in Alleviating Immune Response Activation in Mice Bone Marrow after Irradiation.

Ionizing radiation (IR) induces severe hematopoietic injury by causing DNA and RNA damage as well as activating the immune responses, necessitating the development of effective therapeutic strategies. Ribonuclease L (RNase L) as an innate immune response pathway is triggered by exogenous and endogenous abnormal dsRNA under viral infection and dyshomeostasis, thereby activating the immune responses. Thus, we investigated the effect of RNase L on irradiation-induced bone marrow damage using RNase L knockout (RNase L-/-) mice. Phenotypic analysis revealed that RNase L knockout mitigates irradiation-induced injury in the bone marrow. Further investigation into the mechanism of RNase L by RNA-seq, qRT-PCR, and CBA analysis demonstrated that RNase L deficiency counteracts the upregulation of genes related to immune responses induced by irradiation, including cytokines and interferon-stimulated genes. Moreover, RNase L deficiency inhibits the increased levels of immunoglobulins in serum induced by irradiation. These findings indicate that RNase L plays a role in the immune response induced by irradiation in the bone marrow. This study further enhances our understanding of the biological functions of RNase L in the immune response induced by irradiation and offers a novel approach for managing irradiation-induced bone marrow injury through the regulation of RNase L activation.

Oral Ingestion of Yuzu Seed Oil Suppresses the Development of Atopic Dermatitis-like Skin Lesions in NC/Nga Mice.

Long-term oral ingestion of unheated yuzu seed oil in humans reduces lipid peroxides in the blood. Moreover, yuzu seed oil contains limonin, which can induce antioxidant and anti-inflammatory effects by activating the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Previously, Nrf2 has been shown to reduce atopic dermatitis (AD). Therefore, we hypothesized that ingesting unheated yuzu seed oil can regulate AD through Nrf2. An AD model was established using NC/Nga mice through repeated local exposure to mite antigens. Unheated and purified yuzu seed oil (100 µL/mice) or water (control, 100 µL/mice) was administered orally once a day using a gastric cannula for rodents for 28 days. On day 28, mice in the unheated yuzu seed oil group exhibited significantly lower clinical skin severity scores and ear thickness than those in the purified yuzu seed oil and water groups. Serum histamine levels remained unaltered among the three AD-induced groups. Serum Dermatophagoides farina body (Dfb)-specific immunoglobulin E (IgE) levels were significantly lower in the unheated yuzu seed oil group. Oral ingestion of yuzu seed oil in NC/Nga AD model mice significantly suppressed dermatitis deterioration and decreased serum IgE levels. Clinical trials (n = 41) have already confirmed that unheated yuzu oil is safe for long-term intake, further suggesting its potential use in improving AD symptoms.

Effect of Hita Tenryo Water™, a natural mineral water, on allergic symptoms induced by cedar in mice

The number of patients with allergies to pollen and food is increasing worldwide. In Japan, the prevalence of cedar pollinosis, a type I allergy, is nearly 30% and accounts of hay fever are rising. A potential natural remedy for these allergic diseases may be Hita Tenryo Water™ (referred to simply as Hita Tenryo water), water that is pumped from deep underground in the Hita region of Oita, Japan, which has been the subject of various research reports. Here, we investigated the potential of using Hita Tenryo water to suppress the onset of cedar pollinosis in a mouse model and explored the immunological mechanism of the suppression. Test model mice were given Hita Tenryo water ad libitum to drink and received intraperitoneal administration of (i) tap water (Hw1), (ii) 25% Hita Tenryo water (Hw2) or (iii) 100% Hita Tenryo (Hw3). There were no significant differences in body weight change, feed intake, or water intake among the groups during the experimental period. We examined nose rubbing and sneezing as allergic symptoms. The frequency of rubbing and sneezing tended to decrease in the Hw1 and Hw2 group, and significantly decreased in the Hw3 group compared to control. Total IgE levels in serum were also significantly reduced in Hita Tenryo water intraperitoneal administration groups. In vitro examination of the rate of release of β-hexosaminidase from BL-2H3 cells showed that there were no significantly differences between Hita Tenryo water-treated and control cells. In addition, measurement of Th2-related cytokine levels in concanavalin A-stimulated peripheral blood mononuclear cells revealed a significant decrease in IL-4, IL-6, and IL-10 levels in medium (p < 0.01). In contrast, production of IFN-γ significantly increased (p < 0.01). These results indicate that Hita Tenryo water may alleviate and/or suppress allergic symptoms.

Immune signatures predict response to house dust mite subcutaneous immunotherapy in patients with allergic rhinitis.

Identifying predictive biomarkers for allergen immunotherapy response is crucial for enhancing clinical efficacy. This study aims to identify such biomarkers in patients with allergic rhinitis (AR) undergoing subcutaneous immunotherapy (SCIT) for house dust mite allergy. The Tongji (discovery) cohort comprised 72 AR patients who completed 1-year SCIT follow-up. Circulating T and B cell subsets were characterized using multiplexed flow cytometry before SCIT. Serum immunoglobulin levels and combined symptom and medication score (CSMS) were assessed before and after 12-month SCIT. Responders, exhibiting ≥30% CSMS improvement, were identified. The random forest algorithm and logistic regression analysis were used to select biomarkers and establish predictive models for SCIT efficacy in the Tongji cohort, which was validated in another Wisco cohort with 43 AR patients. Positive SCIT response correlated with higher baseline CSMS, allergen-specific IgE (sIgE)/total IgE (tIgE) ratio, and frequencies of Type 2 helper T cells, Type 2 follicular helper T (TFH2) cells, and CD23+ nonswitched memory B (BNSM) and switched memory B (BSM) cells, as well as lower follicular regulatory T (TFR) cell frequency and TFR/TFH2 cell ratio. The random forest algorithm identified sIgE/tIgE ratio, TFR/TFH2 cell ratio, and BNSM frequency as the key biomarkers discriminating responders from nonresponders in the Tongji cohort. Logistic regression analysis confirmed the predictive value of a combination model, including sIgE/tIgE ratio, TFR/TFH2 cell ratio, and CD23+ BSM frequency (AUC = 0.899 in Tongji; validated AUC = 0.893 in Wisco). A T- and B-cell signature combination efficiently identified SCIT responders before treatment, enabling personalized approaches for AR patients.

Morita-Baylis-Hillman adduct 2-(3-hydroxy-1-methyl-2-oxoindolin-3-il) acrylonitrile (CISACN) ameliorates the pulmonary allergic inflammation in CARAS model by increasing IFN-γ/IL-4 ratio towards the Th1 immune response

Combined allergic rhinitis and asthma syndrome (CARAS) is an airway-type 2 immune response with a profuse inflammatory process widely affecting the world population. Due to the compromise of quality of life and the lack of specific pharmacotherapy, the search for new molecules becomes relevant. This study aimed to evaluate the effectiveness of the Morita-Bailys-Hillman adduct (CISACN) treatment in the CARAS experimental model. Female BALB/c mice were ovalbumin (OVA) -sensitized and -challenged and treated with CISACN. The treatment decreased the eosinophil migration to the nasal and lung cavities and tissues and the goblet cell hyperplasia/hypertrophy, attenuated airway hyperactivity by reducing the hyperplasia/hypertrophy of the smooth muscle and the extracellular matrix's thickness. Also, the treatment reduced the clinical signs of rhinitis as nasal rubbing and sneezing in a histamine-induced nasal hyperreactivity assay. The immunomodulatory effect of CISACN was by reducing OVA-specific IgE serum level, and IL-33, IL-4, IL-13, and TGF-β production, dependent on IFN-γ increase. Furthermore, the effect of CISACN on lung granulocytes was by decreasing the p-p38MAPK/p65NF-κB signaling pathway. Indeed, CISACN reduced the p38MAPK and p65NF-κB activation. These data demonstrated the anti-inflammatory and immunomodulatory effects of the CISACN with scientific support to become a pharmacological tool to treat airway inflammatory diseases.

Immunomodulatory and anti-angiogenesis effects of excavatolide B and its derivatives in alleviating atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin condition primarily driven by T helper 2 (Th2) cytokines, resulting in skin barrier defects, angiogenesis, and inflammatory responses. The marine natural product excavatolide B (EXCB), isolated from the Formosan Gorgonian coral Briareum stechei, exhibits anti-inflammatory and analgesic properties. To enhance solubility, EXCB is chemically modified into the derivatives EXCB-61 salt and EXCB-79. The study aims to investigate the therapeutic effects of these compounds on dinitrochlorbenzene (DNCB)-induced skin damage and to elucidate the underlying anti-inflammatory and anti-angiogenesis mechanism. In vitro, using lipopolysaccharide (LPS)-induced RAW 264.7 cells, all compounds at 10 μM significantly inhibited expression of inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2), vascular endothelial growth factor (VEGF), and cytokines (interleukin (IL)−1β, IL-6, and IL-17A). In vivo, topical application of these compounds on DNCB-induced AD mice alleviated skin symptoms, reduced serum levels of IgE, IL-4, IL-13, IL-17, and interferon-γ, and moderated histological phenomena such as hyperplasia, inflammatory cell infiltration, and angiogenesis. The three compounds restored the expression of skin barrier-related proteins (loricrin, filaggrin, and claudin-1) and reduced the expression of angiogenesis-related proteins (VEGF and platelet endothelial cell adhesion molecule-CD31) in the tissues. This is the first study to indicate that EXCB, EXCB-61 salt, and EXCB-79 can treat AD disease by reducing inflammation and angiogenesis. Hence, they may be considered potential candidates for the development of new drugs for AD.

Regulatory T and B cells in pediatric Henoch–Schönlein purpura: friends or foes?

Background and objectivesHenoch–Schönlein purpura (HSP) is the most common immunoglobulin A-mediated systemic vasculitis in childhood. We studied immune dysregulation in HSP by analyzing regulatory T (Treg), T helper 3 (Th3), and regulatory B cell (Breg) subpopulations that might intervene in immune activation, IgA production, and HSP clinical manifestations.MethodsThis prospective study included 3 groups of children: 30 HSP on acute phase, 30 HSP on remission, and 40 healthy controls (HCs) matched on age. Treg, Breg, and Th3 were analyzed by flow cytometry. Serum immunoglobulin and cytokine levels were quantified by ELISA and Luminex.ResultsTreg frequencies were higher in acute HSP than in remitting HSP and HCs (6.53% [4.24; 9.21] vs. 4.33% [3.6; 5.66], p = 0.002, and vs. 4.45% [3.01; 6.6], p = 0.003, respectively). Activated Th3 cells (FoxP3 + Th3 cells) tend to be more abundant in HSP than in HCs (78.43% [50.62; 80.84] vs. 43.30% [40.20; 49.32], p = 0.135). Serum IgA, IL-17, and latency-associated peptide (a marker of the anti-inflammatory cytokine TGF-beta production) were significantly and inflammatory cytokines TNF-alpha, IL-1-beta, and IL-6 were non-significantly higher in HSP than HCs. Bregs were identical between the groups, but, in patients with renal impairment, Breg percentage was lower compared to those without. Treg removal in PBMC culture resulted in an increase in IgA production in HSP proving a negative regulatory role of Tregs on IgA production.ConclusionsIn pediatric HSP, immune activation persists in spite of an increase in Th3 and Tregs. Th3 could be involved in IgA hyperproduction, inefficiently downregulated by Tregs. Lack of Bregs appears linked to renal impairment.

Immunoglobulin replacement therapies in inborn errors of immunity: a review.

Immunoglobulins (Ig) were used as a therapeutic modality for the first time in a patient with X-linked agammaglobulinemia in 1952 by Colonel Ogden Bruton, decades before the molecular mechanisms causing the disease were unraveled. In many autoimmune and inflammatory illnesses, human immunoglobulin has been employed as a significant immunomodulatory and immunosuppressive drug. In patients with inborn errors of immunity (IEI), immunoglobulin remains a cornerstone of management. IEIs are notable causes of recurrent infections and autoimmunity due to inheritable single-gene defects in genes encoding for different components of the immune system. As there is decreased immunoglobulin production in IEIs with antibody defects, immunoglobulin replacement is the mainstay of therapy in these disorders. Although serum immunoglobulin levels may not be low in combined immune defects, immunoglobulin replacement is still necessary in these disorders due to a deficiency of functional antibodies and qualitative defects of immunoglobulins. Commercial immunoglobulin preparations are generated from plasma donated by thousands of donors. Immunoglobulin preparations are usually available in two forms: intravenous and subcutaneous immunoglobulins. In the developed world, both intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (SCIg) are available, and SCIg is preferred over IVIg for replacement therapy in patients with IEIs. In developing countries, IVIg remains the mainstay of replacement therapy. The rate of adverse events has significantly reduced over the last few years due to advancements in the production process. In this review article, we discuss different aspects of the use of Ig (indications, dosing, mechanism of action, route, adverse effects) in patients with IEIs.

MULTIPLE GIANT CHALAZIA IN HYPERIMMUNOGLOBULINEMIA E SYNDROME: A CASE REPORT

Introduction : Hyperimmunoglobulinemia E syndrome (HIES) is a rare primary immunodeficiency disorder that manifests as elevated level of serum immunoglobulin E (IgE) higher than 1.000 IU/mL and multisystem disorder characterized by recurrent skin and pulmonary abscesses caused by autosomal dominant or recessive disorder with gene mutation. We present a case of multiple giant chalazion ina patient with HIES.&#x0D; Case Illustration : A 15-year-old boy was referred to Ophthalmology Department with multiple giant lumps on the left eyelid for the last 2 weeks. He had a history of recurrent multiple lumps on the left lower eyelid in the last 1 year. He was diagnosed with HIES since 8 years ago. He had normal visual acuity of both eyes. Multiple giant chalazion were observed on the left upper and lower eyelid. The patient also presented with scalp and neck infection. Laboratory studies showed elevated total serum IgE level of 53,032 IU/mL and eosinophilia.&#x0D; Discussion : Ocular manifestations in HIES patients are not common. Some cases reported chalazia, keratoconus, and blepharitis. Surgical incision drainage was performed in our patient. Medications and surgical intervention had produced only transient improvement. The patient was treated conservatively. Riskof chalazia recurrence remains unknown as reported cases presented with diverse clinical presentation and follow-up serum IgE evaluation is not routinely performed.&#x0D; Conclusion : Recurrent multiple giant chalazia may occur as an ophthalmic feature of HIES. HIES should be considered and investigated in patients presenting with recurrent giant chalazia.

MULTIPLE GIANT CHALAZIA IN HYPERIMMUNOGLOBULINEMIA E SYNDROME: A CASE REPORT

Abstract&#x0D; Introduction : Hyperimmunoglobulinemia E syndrome (HIES) is a rare primary immunodeficiency disorder that manifests as elevated level of serum immunoglobulin E (IgE) higher than 1.000 IU/mL and multisystem disorder characterized by recurrent skin and pulmonary abscesses caused by autosomal dominant or recessive disorder with gene mutation. We present a case of multiple giant chalazion ina patient with HIES.&#x0D; Case Illustration : A 15-year-old boy was referred to Ophthalmology Department with multiple giant lumps on the left eyelid for the last 2 weeks. He had a history of recurrent multiple lumps on the left lower eyelid in the last 1 year. He was diagnosed with HIES since 8 years ago. He had normal visual acuity of both eyes. Multiple giant chalazion were observed on the left upper and lower eyelid. The patient also presented with scalp and neck infection. Laboratory studies showed elevated total serum IgE level of 53,032 IU/mL and eosinophilia.&#x0D; Discussion : Ocular manifestations in HIES patients are not common. Some cases reported chalazia, keratoconus, and blepharitis. Surgical incision drainage was performed in our patient. Medications and surgical intervention had produced only transient improvement. The patient was treated conservatively. Riskof chalazia recurrence remains unknown as reported cases presented with diverse clinical presentation and follow-up serum IgE evaluation is not routinely performed.&#x0D; Conclusion : Recurrent multiple giant chalazia may occur as an ophthalmic feature of HIES. HIES should be considered and investigated in patients presenting with recurrent giant chalazia.