Serum IgE Levels Research Articles

Fluconazole worsened lung inflammation, partly through lung microbiome dysbiosis in mice with ovalbumin-induced asthma

Innate immunity in asthma may be influenced by alterations in lung microbiota, potentially affecting disease severity. This study investigates the differences in lung inflammation and microbiome between asthma-ovalbumin (OVA) administered with and without fluconazole treatment in C57BL/6 mice. Additionally, the role of inflammation was examined in an in vitro study using a pulmonary cell line. At 30 days post-OVA administration, allergic asthma mice exhibited increased levels of IgE and IL-4 in serum and lung tissue, higher pathological scores, and elevated eosinophils in bronchoalveolar lavage fluid (BALF) compared to control mice. Asthma inflammation was characterized by elevated serum IL-6, increased lung cytokines (TNF-α, IL-6, IL-10), and higher fungal abundance confirmed by polymerase chain reaction (PCR). Fluconazole-treated asthma mice displayed higher levels of cytokines in serum and lung tissue (TNF-α and IL-6), increased pathological scores, and a higher number of mononuclear cells in BALF, with undetectable fungal levels compared to untreated mice. Lung microbiome analysis revealed similarities between control and asthma mice; however, fluconazole-treated asthma mice exhibited higher Bacteroidota levels, lower Firmicutes, and reduced bacterial abundance. Pro-inflammatory cytokine production was increased in supernatants of the pulmonary cell line (NCI-H292) after co-stimulation with LPS and beta-glucan (BG) compared to LPS alone. Fluconazole treatment in OVA-induced asthma mice exacerbated inflammation, partially due to fungi and Gram-negative bacteria, as demonstrated by LPS+BG-activated pulmonary cells. Therefore, fluconazole should be reserved for treating fungal asthma rather than asthma caused by other etiologies.

Characterizing Non-T2 Asthma: Key Pathways and Molecular Implications Indicative of Attenuated Th2 Response.

Non-Type 2 (non-T2) asthma is characterized by a lack of allergic sensitization and normal to low total IgE levels. We aimed to explore molecular mechanisms and pathways differentiating non-T2 from T2-high pediatric asthma. We analyzed peripheral blood RNA samples from 11 non-T2 and 17 T2-high pediatric asthma patients using bulk RNA sequencing. Differentially expressed genes (DEGs) were identified, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and Protein-Protein Interaction (PPI) network construction. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) were employed to explore significance of these DEGs. We utilized independent public datasets GSE145505 to validate our findings. We investigated Th cytokine profiles in an independent cohort of pediatric patients with non-T2 asthma (n = 38) and T2-high asthma (n = 64). We demonstrated that the total serum IgE levels of children with non-T2 asthma (128.4 ± 159.5IU/mL) was significantly lower than that of those with T2-high asthma (405.8 ± 252.1IU/mL). Our analysis revealed 136 DEGs distinguishing non-T2 from T2-high asthma. IPA identified predicted inhibition of IgE-FcεRI signaling pathways in non-T2 asthma. Our DEG data showed the expression of IGHV4-39, IGLV1-40, IGLV1-47, IGLV1-44, IGHV1-69, IGLV6-57, IGLV3-19, IGLV3-1, and IGLC7 were downregulated in our non-T2 asthma patient. The non-T2 group exhibited significantly higher concentrations of IL-2, IFN-γ, IL-6, and IL-17A compared to the T2-high group. Our integrated analysis differentiated non-T2 from T2-high asthma by revealing downregulation of specific immunoglobulin genes influencing FcεRI signaling, elevated Th1 cytokines and Th17 cytokines might affect IgE associated sensitization and alter Th2 allergic response.

IgE immunoadsorption: technical background, functionality, and first clinical experience

Summary Background The prevalence of allergic diseases has risen in the 21st century, drawing attention to specific therapeutic and preventive strategies. Due to the key role of immunoglobulin E (IgE) in the development of allergic reactions, IgE represents a key target treatment. In this scenario, IgE immunoadsorption (IgE-IA) has been investigated as a procedure that selectively removes circulating IgE antibodies from the bloodstream of patients with atopy. Methods This narrative review aims to critically summarize the current insights regarding IgE-IA in the context of the management of allergic diseases, ranging from the rationale to the technical aspects, as well as the benefits and unmet needs. Results IgE-IA might be a treatment strategy in well-selected patients with allergic diseases. IgE depletion through sessions of IgE-IA results in immediate clinical improvement and might be useful in acute situations when a rapid clinical response is required or when classic approaches are contraindicated or ineffective. Due to the reduced effectiveness over time, IgE-IA could be a valid first approach before starting another IgE depletion therapy, such as omalizumab, when its commencement would otherwise be contraindicated by too-high serum IgE levels. Conclusion Overall, IgE-IA is safe and well tolerated; however, this procedure is currently difficult to implement in routine clinical practice because of costs, time demands, need for hospitalization, and the invasiveness of the procedure, with the associated risks related to the necessity of venous catheterization.

Влияние избыточной массы тела и ожирения на спирометрические, гематологические показатели, уровень общего иммуноглобулина Е и интерлейкина-6 в сыворотке крови у детей и подростков с бронхиальной астмой

There is undoubtedly insufficient number of studies dedicated to the interleukin-6 (IL-6) in blood serum of children and adolescents with bronchial asthma (BA) and those are contradictory. Connection between the IL-6 serum level and systemic markers of type 2 inflammation in BA in children and adolescents depending on the nutritional status remains a subject to discussion as well. The purpose of this research was to study the effect of excess body weight (BW) and obesity on spirometric, hematological parameters, total immunoglobulin E (IgE), IL-6 levels in blood serum of children and adolescents with BA. Materials and methods used: a single-center observational cross-sectional pilot study of 76 adolescents aged 6 to 17 y/o (75% (57) boys) with BA was conducted. All were measured for anthropometric and spirometric parameters, body composition, hematological parameters, total IgE and IL-6 levels in blood serum. Dysanapsis was diagnosed when three conditions were simultaneously met: 1. high or high-to-normal zFVC (above 0.674), 2. normal zFEV1 (above -1.645), and 3. low FEV1/FVC index (below 80%). Results: the number of monocytes (109/l) in peripheral blood and the serum IL-6 level (pg/ml) were statistically significantly higher in the group of patients with overweight and obesity compared to patients with underweight/normal BW (0.55 [0.49; 0.77] v 0.51 [0.42; 0.58], p=0.043 and 1.99 [1.20; 5.78] v 1.28 [0.31; 2.43], p=0.002, respectively). In patients with excess BW and obesity, an inverse statistically significant relationship was found between the serum IL-6 level, zFEV1/FVC and the dysanapsis ratio (R=-0.53, p=0.009, R=-0.61, p=0.002, respectively). Conclusion: formation of an obstructive pattern in children and adolescents with BA with excess BW and obesity may be associated with non-T2-dependent inflammatory mechanisms.

Association of immunoglobulin E levels with glioma risk and survival.

Previous epidemiologic studies have reported an association of serum immunoglobulin E (IgE) levels with reduced glioma risk, but the association between IgE and glioma prognosis has not been characterized. This study aimed to examine how sex, tumor subtype, and IgE class modulate the association of serum IgE levels with glioma risk and survival. We conducted a case-control study using participants from the University of California, San Francisco Adult Glioma Study (1997-2010). Serum IgE levels for total, respiratory and food allergy were measured in adults diagnosed with glioma (n = 1319) and cancer-free controls (n = 1139) matched based on age, sex, and race and ethnicity. Logistic regression was adjusted for patient demographics to assess the association between IgE levels and glioma risk. Multivariable Cox regression adjusted for patient-specific and tumor-specific factors compared survival between the elevated and normal IgE groups. All statistical tests were 2-sided. Elevated total IgE was associated with reduced risk of IDH-wildtype (RR = 0.78, 95% CI: 0.71-0.86) and IDH-mutant glioma (RR = 0.73, 95% CI: 0.63-0.85). In multivariable Cox regression, positive respiratory IgE was associated with improved survival for IDH-wildtype glioma (RR = 0.79, 95% CI: 0.67-0.93). The reduction in mortality risk was significant in females only (RR = 0.75, 95% CI: 0.57-0.98) with an improvement in median survival of 6.9 months (P<.001). Elevated serum IgE was associated with improved prognosis for IDH-wildtype glioma, with a more pronounced protective effect in females than males, which has implications for the future study of IgE-based immunotherapies for glioma.

Treatment of refractory immune-mediated necrotizing myopathy with efgartigimod

ObjectiveWe aimed to explore the efficacy and safety of efgartigimod in patients with refractory immune-mediated necrotizing myopathy (IMNM).MethodsThis open-label pilot observational study included seven patients with refractory IMNM, all of whom received intravenous efgartigimod treatment. The clinical response was assessed after 4 weeks of efgartigimod treatment according to the 2016 American College of Rheumatology–European League Against Rheumatism response criteria for adult idiopathic inflammatory myopathy. Serum levels of immunoglobulin as well as anti–signal recognition particle (SRP) and anti–3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies were measured using enzyme-linked immunosorbent assays and commercial line immunoblot assays. Safety assessments included evaluations of adverse events and severe adverse events.ResultsThe seven patients with refractory IMNM included five cases with anti-HMGCR antibodies and two cases within anti-SRP antibodies. Four of the seven patients achieved clinical responses. The total improvement score for the responders at 4 weeks were 32.5, 40.0, 47.5, and 70.0, and those at 8 weeks were 27.5, 47.5, 57.5, and 70.0. In comparison to the responsive patients, the non-responsive patients had longer durations [8 (-) versus 2 (1–5) years, P = 0.03], and more chronic myopathic features by muscle biopsy (67% versus 0%, P = 0.046). Serum immunoglobulin G levels (11.2 ± 2.5 versus 5.7 ± 2.5, P = 0.007) and anti-HMGCR/SRP antibody levels (97.2 ± 6.9 versus 41.8 ± 16.8, P = 0.002) were decreased after treatment compared with baseline levels. Adverse events were reported in one of the seven patients, who showed mild headache.ConclusionsDespite its small size, our study demonstrated that promoting the degradation of endogenous immunoglobulin G may be effective for patients with IMNM. Efgartigimod may be a promising option for cases of refractory IMNM to shorten duration and minimize chronic myopathic features.

Nephrotic Syndrome and Recurrent Infection

Nephrotic syndrome is characterized by the leakage of protein from the blood into the urine along with the triad of proteinuria, albuminuria, and peripheral edema. Loss of protein leads to the loss of immunoglobulin and complements. X-linked agammaglobulinemia (XLA), or Bruton disease, is a primary immunodeficiency disease caused by a defect in the development of B cells in the bone marrow and a low serum level of immunoglobulins. The present case involves a 12-year-old boy with nephrotic syndrome, osteomyelitis, and recurrent infections. We discovered that he had XLA. This report underscores the importance of considering inborn errors of immunity in cases of protein loss, such as nephrotic syndrome.

Therapeutic potential of plasma-treated solutions in atopic dermatitis

Atopic Dermatitis (AD) is a prevalent inflammatory skin disease that is currently incurable. Plasma-treated solutions (PTS) (e.g., culture media, water, or normal saline, previously exposed to plasma) are being studied as novel therapy. Recently, PTS is gaining attention due to its advantages over non-thermal plasma (also known as cold atmospheric plasma). Thus, we explore the application of PTS in treating AD. In vivo experiments demonstrated that PTS significantly alleviated AD-like symptoms. It reduced mast cell and macrophage infiltration, decreased scratching times and serum IgE levels. These therapeutic effects of PTS on AD mice were associated with the activation of the antioxidant molecule Nrf2. In vitro experiments revealed that PTS could decrease ROS level and regulate cytokine expression (such as IL-6, IL-10, IL-13 and CCL17) in TNF-α/IFN-γ-stimulated keratinocytes and LPS-stimulated M1 macrophages. Additionally, PTS could upregulate the expression of antioxidant stress molecules such as Nrf2, HO-1, NQO1 and PPAR-γ in both cell types. Overall, PTS demonstrated potent therapeutic potential for AD without notable side effects. Our research provided a promising approach to AD treatment and may serve as a potential therapeutic strategy in other inflammatory skin diseases.

Pathophysiology of Congenital High Production of IgE and Its Consequences: A Narrative Review Uncovering a Neglected Setting of Disorders.

Elevated serum IgE levels serve as a critical marker for uncovering hidden immunological disorders, particularly inborn errors of immunity (IEIs), which are often misdiagnosed as common allergic conditions. IgE, while typically associated with allergic diseases, plays a significant role in immune defense, especially against parasitic infections. However, extremely high levels of IgE can indicate more severe conditions, such as Hyper-IgE syndromes (HIES) and disorders with similar features, including Omenn syndrome, Wiskott-Aldrich syndrome, and IPEX syndrome. Novel insights into the genetic mutations responsible for these conditions highlight their impact on immune regulation and the resulting clinical features, including recurrent infections, eczema, and elevated IgE. This narrative review uniquely integrates recent advances in the genetic understanding of IEIs and discusses how these findings impact both diagnosis and treatment. Additionally, emerging therapeutic strategies, such as hematopoietic stem cell transplantation (HSCT) and gene therapies, are explored, underscoring the potential for personalized treatment approaches. Emphasizing the need for precise diagnosis and tailored interventions aims to enhance patient outcomes and improve the quality of care for those with elevated IgE levels and associated immunological disorders.

Impact of Dupilumab on Skin Surface Lipid-RNA Profile in Severe Asthmatic Patients.

The analysis of skin surface lipid-RNAs (SSL-RNAs) provides a non-invasive method for understanding the molecular pathology of atopic dermatitis (AD), but its relevance to asthma remains uncertain. Although dupilumab, a biologic drug approved for both asthma and AD, has shown efficacy in improving symptoms for both conditions, its impact on SSL-RNAs is unclear. This study aimed to investigate the impact of dupilumab treatment on SSL-RNA profiles in patients with severe asthma. An SSL-RNA analysis was performed before and after administering dupilumab to asthma patients requiring this intervention. Skin samples were collected non-invasively from patients before and after one year of dupilumab treatment. Although 26 patients were enrolled, an SSL-RNA analysis was feasible in only 7 due to collection challenges. After dupilumab treatment, improvements were observed in asthma symptoms, exacerbation rates, and lung function parameters. Serum levels of total IgE and periostin decreased. The SSL-RNA analysis revealed the differential expression of 218 genes, indicating significant down-regulation of immune responses, particularly those associated with type 2 inflammation, suggesting potential improvement in epithelial barrier function. Dupilumab treatment may not only impact type 2 inflammation but also facilitate the normalization of the skin. Further studies are necessary to fully explore the potential of SSL-RNA analysis as a non-invasive biomarker for evaluating treatment response in asthma.

Blood eosinophil count correlates with alveolar damage in emphysema-predominant COPD

BackgroundAlthough blood eosinophil count is recognized as a useful biomarker for the management of chronic obstructive pulmonary disease (COPD), the impact of eosinophils in COPD has not been fully elucidated. Here we aimed to investigate the relationships between the blood eosinophil count and various clinical parameters including lung structural changes.MethodsNinety-three COPD patients without concomitant asthma were prospectively enrolled in this study. Blood eosinophil count, serum IgE level, serum periostin level, and chest computed tomography (CT) scans were evaluated. Eosinophilic COPD was defined as COPD with a blood eosinophil count ≧ 300/µL. We examined the correlation between the blood eosinophil count and structural changes graded by chest CT, focusing specifically on thin airway wall (WT thin) and thick airway wall (WT thick) groups. In a separate cohort, the number of eosinophils in the peripheral lungs of COPD patients with low attenuation area (LAA) on chest CT was assessed using lung resection specimens.ResultsThe mean blood eosinophil count was 212.1/µL, and 18 patients (19.3%) were categorized as having eosinophilic COPD. In the whole group analysis, the blood eosinophil count correlated only with blood white blood cells, blood basophils, C-reactive protein level, and sputum eosinophils. However, the blood eosinophil count positively correlated with the percentage of LAA and negatively correlated with the diffusing capacity for carbon monoxide in the WT thin group. Lung specimen data showed an increased number of eosinophils in the peripheral lungs of COPD patients with LAA on chest CT scans compared to normal controls.ConclusionsSome COPD patients without concomitant asthma showed a phenotype of high blood eosinophils. Alveolar damage may be related to eosinophilic inflammation in patients with COPD without asthma and thickening of the central airway wall.

The Relationship Between Serum IgE Level and IL-4 and IL-13 Cytokines in Colorectal Cancer Patients

ABSTRACT Background Colorectal cancer (CRC) is the most common malignancy of the digestive system in the world. Immune cells and molecules in tumor microenvironment are crucial.Identifying immune system components in cancer aids in biomarker discovery. This study investigated the serum IgE levels and expression of IL-4 and IL-13 in the tissue and serum of CRC patients and explored their possible association with pathological and clinical factors. Materials and methods Thirty-six patients with CRC and 36 healthy individuals were involved in the study. Tissues and blood samples were collected. Serum levels of IgE and IL-4 and IL-13 were analyzed using the ELISA method. The quantitative Real-Time PCR (qRT-PCR) technique was used to assess the expression levels of the cytokines in CRC tissue samples in comparison with the adjacent control tissue. Results Our results revealed that the serum level of IL-4 and IL-13 and also their gene expression levels were significantly decreased in CRC patients compared to the controls. The results of this study revealed that there is no significant difference in the serum levels of IgE between CRC patients and the control group. Conclusion All in all, the results of the current research suggest that the expression levels of IL-13, IL-4, and IgE vary between CRC tissue.

Hematopoietic PI3Kδ deficiency aggravates murine atherosclerosis through impairment of regulatory T cells.

Chronic activation of the adaptive immune system is a hallmark of atherosclerosis. As PI3Kδ is a key regulator of T and B-cell differentiation and function, we hypothesized that alleviation of adaptive immunity by PI3Kδ inactivation may represent an attractive strategy counteracting atherogenesis. As expected, lack of hematopoietic PI3Kδ in atherosclerosis-prone Ldlr-/- mice resulted in hindered T- and B-cell numbers, CD4+ effector T cells, Th1 response, and immunoglobulin levels. However, despite markedly impaired peripheral proinflammatory Th1 cells and atheromatous CD4+ T cells, the unexpected net effect of hematopoietic PI3Kδ deficiency was aggravated vascular inflammation and atherosclerosis. Further analyses revealed that PI3Kδ deficiency impaired numbers, immunosuppressive functions, and stability of regulatory CD4+ T cells (Tregs), whereas macrophage biology remained largely unaffected. Adoptive transfer of wild-type Tregs fully restrained the atherosclerotic plaque burden in Ldlr-/- mice lacking hematopoietic PI3Kδ, whereas PI3Kδ deficient Tregs failed to mitigate disease. Numbers of atheroprotective B-1 and proatherogenic B-2 cells as well serum immunoglobulin levels remained unaffected by adoptively transferred wild-type Tregs. In conclusion, we demonstrate that hematopoietic PI3Kδ ablation promotes atherosclerosis. Mechanistically, we identified PI3Kδ signaling as a powerful driver of atheroprotective Treg responses, which outweigh PI3Kδ driven proatherogenic effects of adaptive immune cells like Th1 cells.

High malignancy rate in IgE-deficient children.

Recent epidemiological studies have increasingly highlighted the antitumor efficacy of IgE owing to the increased malignancy rate in IgE-deficient patients. The purpose of this study, the largest for children, was to determine whether malignant diagnoses in children are associated with IgE deficiency (IgE <2.5 kIU/L). A total of 6821 pediatric patients were reviewed, focusing on patients with IgE below 2.5 kIU/L (n = 599). The causes of IgE testing were evaluated by categorizing them as having cancer, allergies, suspected or diagnosed immunodeficiency, and other conditions. In all but one patient with malignancy, IgE levels were measured after the diagnosis of the disease. Malignancies were observed much more frequently in the low IgE group than in the normal group (10/599, 1.7% and 7/6222, 0.11%; OR = 15.07; 95% CI: 5.72-39.75; p <.0001). According to our analysis, 70% of the patients had leukemia/lymphoma, which is consistent with studies showing that hematologic malignancies are the most frequent cancers linked to IgE deficiency. No increase in the prevalence of cancer was observed in IgE-deficient patients with suspected or diagnosed immunodeficiency. In conclusion, we observed a higher rate of previous malignancy (particularly hematologic cancer) in children with low serum IgE levels. Larger investigations would offer insightful information about the function of low IgE levels in predicting malignancy risk and improving the present diagnostic procedures.

Effects of Tralokinumab on Clinical and Laboratory Indexes in Atopic Dermatitis: A 24-Week Real-World Study.

Background: Tralokinumab, a monoclonal anti-IL-13 antibody, is approved for treating atopic dermatitis (AD). Real-world data on its effectiveness and safety are limited. Objective: To evaluate the real-world effectiveness and safety of tralokinumab and the transition of laboratory indexes during 24-week treatment for AD patients. Methods: This retrospective study included 104 patients with moderate-to-severe AD treated with tralokinumab 300 mg every 2 weeks after primary 600 mg. Clinical and laboratory indexes were assessed until week 24. Results: At week 24, achievement rates of Eczema Area and Severity Index 75 (EASI 75), EASI 90, and investigator's global assessment 0 out of 1 in systemic therapy-naïve patients, 83.3%, 72.2%, and 44.4%, respectively, were higher than those in systemic therapy-experienced patients, 46.7%, 20.0%, and 6.7%, respectively. Serum levels of immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and lactate dehydrogenase (LDH) significantly decreased at week 24, whereas neutrophil-to-lymphocyte ratio (NLR) and systemic inflammation response index (SIRI) significantly decreased at week 12 from baseline. Twenty-nine patients (27.9%) experienced mild treatment-emergent adverse events. Conclusions: Tralokinumab treatment showed prosperous therapeutic effects and good tolerability in real-world practice for AD, with higher effectiveness in patients without prior systemic therapy compared with those with prior systemic therapy. Tralokinumab treatment significantly decreased clinical and laboratory indexes, EASI, Peak Pruritus-Numerical Rating Scale, IgE, TARC, LDH, NLR, and SIRI.

Predominantly antibody deficiencies: An important underlying cause of recurrent pneumonia in adults

RATIONALE Limited information exists concerning the causes of recurrent pneumonia in adults, particularly regarding immunodeficiencies or inborn errors of immunity. OBJECTIVES This study aims to evaluate the etiology of recurrent pneumonia in the adult population, with a focus on humoral deficiency and inborn errors of immunity. METHODS A cross-sectional non-interventional study was conducted in Cali, Colombia, from January 2019 to March 2021. Consecutive patients, aged over 14 years but under 65 years, with a history of recurrent pneumonia, were included after providing consent. The study involved a thorough review of their past medical records and radiological studies. All participants underwent complete blood count and serum immunoglobulin level measurements (IgG, IgA, IgM and IgE). Further testing was carried out based on the evaluation of a clinical immunologist. RESULTS Sixty-six (66) individuals, comprising 34 females and 32 males, were enrolled in the study. The onset of symptoms occurred at an average age of 14 years (ranging from 5 to 36 years). The analysis revealed that the most prevalent cause of recurrent pneumonia was inborn errors of immunity (20 cases, 30.3%), followed by idiopathic (9 cases, 13.7%), bronchiectasis (7 cases, 10.7%), primary ciliary dyskinesia (6 cases, 9.0%), asthma (6 cases, 9.0%), and post-tuberculosis complications (5 cases, 7.6%). CONCLUSION Predominantly antibody deficiencies, along with other inborn errors of immunity, were identified as an important factor contributing to recurrent pneumonia in adults. These findings highlight the importance of these conditions as major etiological factors in the context of recurrent pneumonia in the Colombian adult population.

The prevalence of patients suffering from chronic spontaneous urticaria, in whom omalizumab cannot be stopped even after six years.

Omalizumab (OMA) was the first FDA-approved biological drug for severe chronic spontaneous urticaria (CSU), and until today is the only beneficial and truly safe one. The objectives were: To assess the prevalence of CSU patients in whom OMA cannot be stopped over time. We also asked if biomarkers (e.g., anti-TPO antibodies and total IgE) could assist in anticipating this issue. We used our prospective registry of 93 patients, which included CSU disease duration, the onset of OMA treatment, Urticaria Activity Score (UAS7) during follow-up, co-morbidities, serum IgE levels and the presence of anti-TPO antibodies. Finally, we assessed the response to OMA during a period of six years. Out of the 93 treated CSU patients, OMA was stopped in ten patients after six months being defined as failures. In another ten patients, OMA was discontinued after 2-4 years of therapy, achieving a remission. Seventy-three patients are still treated between 2 and 6 years, having different degrees of response. Of these, in thirty-eight (52%) patients, we could not stop OMA even after six years due to CSU relapses. The prevalence of lower serum IgE levels and anti-TPO antibody positivity was significantly higher in CSU patients in whom OMA could not be stopped. This is the first study where OMA-treated CSU patients were followed up to six years. In half of them, long-term therapy of six years is still required.

Dietary supplementation of Astragalus flavonoids regulates intestinal immunology and the gut microbiota to improve growth performance and intestinal health in weaned piglets.

Astragali Radix (AS) is a widely used herb in traditional Chinese medicine, with calycosin as its main isoflavonoid. Our previous study discovered that calycosin triggers host defense peptide (HDP) production in IPEC-J2 cells. The aim of this study is to investigate the alleviation effects of AS total flavone and AS calycosin on growth performance, intestinal immunity, and microflora in weaned piglets. Sixty-four piglets were assigned randomly to 4 treatment groups, (1) CON: the basal diet, (2) P-CON: the basal diet plus antibiotics (1 g/kg), (3) AS-TF: the basal diet plus AS total flavone at 60 mg/day per piglet, (4) AS-CA: the basal diet plus AS calycosin at 30 mg/day per piglet. Each treatment consists of 4 replicates with 4 piglets per replicate. Results showed that treatment with AS-TF and AS-CA enhanced average daily growth and average daily feed intake compared to the CON group (P < 0.01), while AS-CA significantly reduced the diarrhea rate (P < 0.05). Both AS-TF and AS-CA significantly increased serum immunoglobulin (Ig) A and IgG levels, with AS-CA further boosting intestinal mucosal secretory IgA levels (P < 0.05). Histological analysis revealed improvements in the morphology of the jejunum and ileum and goblet cell count by AS-TF and AS-CA (P < 0.05). Supplementation of AS-TF and AS-CA promoted the expression of several intestinal HDPs (P < 0.05), and the effect of AS-CA was better than that of AS-TF. In addition, the AS-TF and AS-CA regulated jejunal microbial diversity and composition, with certain differential bacteria genera were showing high correlation with serum cytokines and immunoglobulin levels, suggesting that the intestinal flora affected by AS-TF and AS-CA may contribute to host immunity. Overall, AS CA and AS TF all improved growth performance and health, likely by enhancing nutrition digestibility, serum and intestinal immunity, and intestinal microbial composition. They showed the similar beneficial effect, indicating AS CA appears to be a major compound contributing to the effects of AS TF. This study demonstrated the positive effect of AS flavonoids on weaned piglets and provided a scientific reference for the efficient use of AS products.

Unveiling Potent Anti-Asthmatic Effect of Curcumin in Combination with Salmeterol in Swiss Albino Mice

Background: Asthma is a long-term inflammatory respiratory condition marked by alterations in the airways and an increase in inflammatory cell infiltration. It has been observed that Curcumin possesses immune-modulating, anti-inflammatory, and relaxing properties for smooth muscle in the airways. Salmeterol is believed to ease the smooth muscles of the airways. Objective: Swiss Albino mice were used in the research to examine the combination anti-asthmatic effects of Curcumin and Salmeterol in asthma produced by ova albumin and milk induced eosinophilia and leucocytosis. Methods: The mice received pre-treatment with Curcumin (10 mg/kg, 20 mg/kg intraperitoneally) as well as Salmeterol (5 mg/kg) after being stimulated with an Ovalbumin (OVA) challenge and milk. After the induction period, various hematological, biochemical, molecular (ELISA), and histological analyses were performed. Results: The findings demonstrated that the combined treatment decreased the animal’s overall leukocyte and eosinophil numbers in a manner that was dose-dependent. Additionally, the therapy reduced albumin and overall protein amount in serum, BALF and lung tissues, facilitated changes in haematological parameters, and reduced the rise of Th2 cytokines (IL-4, TNF-α, IL-13) levels that is induced by OVA in lungs and BALF, total IgE level in serum. The combined action of Curcumin and Salmeterol reduced OVA-induced inflammatory influx and ultrastructural abnormalities, according to histopathological evaluation. Conclusion: The findings of this investigation demonstrate that curcumin and salmeterol together possess anti-asthmatic effects through suppressing Th2 triggered immune response and possessing an anti-inflammatory effect and anti-allergic effect. Thus combination of treatments might be a novel technique for managing asthma.

Development of fast-dissolving sublingual nanofibers containing allergen and curcumin for immune response modulation in a mouse model of allergic rhinitis.

Curcumin (CUR) has been considered a potential therapeutic agent for allergic reactions due to its antioxidant and anti-inflammatory activities. Nanofibers have attracted increasing attention in drug delivery. The aim of this study was to investigate the combined therapeutic effects of curcumin and allergen in nanofiber-based treatments in order to increase the effectiveness of sublingual immunotherapy (SLIT) efficacy in a mouse model of allergic rhinitis. Nanofibers containing CUR (1.25% and 2.5%) and ovalbumin 2% (OVA) as an allergen were prepared via electrospinning and characterized. BALB/c mice were sensitized with OVA to the induced allergic rhinitis model. SLIT with free and/or nanofibers was carried out. IL-4, INF-γ, and IgE serum levels were measured using ELISA. Splenocyte proliferation was evaluated by the MTT assay. Lung and nasal histological examinations and nasal lavage fluid (NALF) cell counting were carried out. Nanofibers containing 1.25% CUR and 2% OVA were chosen as the optimal formulations. SLIT treatment with the CUR and OVA nanofiber co-administration led to a significantly decreased serum IgE. Nanofiber containing 2.5 µg of CUR/mouse combined with OVA nanofiber showed a significant decrease in IL-4 and an increase in IFN-γ compared to other groups. NALF assessment showed a significant decrease in specific cell and eosinophil counts in the treated nanofiber groups. The histopathological results of NAL in the optimal formulations were near normal, with diminished cellular infiltration and inflammation. Our findings suggest that co-sublingual administration of allergen and CUR nanofibers can be considered as potential immunomodulatory agents.