Role Of Immunoglobulin Research Articles

Endothelin Inhibitors in Chronic Kidney Disease: New Treatment Prospects.

The endothelin system is reported to play a significant role in glomerular and tubulointerstitial kidney disease. In the kidney, endothelins are produced in mesangial cells and the glomerular basement membrane by the endothelium and podocytes. The endothelin system regulates glomerular function by inducing proliferation, increasing permeability and in effect proteinuria, and stimulating inflammation, tubular fibrosis, and glomerular scarring. Endothelin A receptor antagonists have been proven to delay the progression of chronic kidney disease and play a protective role in immunoglobulin A nephropathy, focal segmental glomerulosclerosis, and diabetic nephropathy. There are several ongoing research studies with ETAR antagonists in nondiabetic nephropathy, Alport disease, vasculitis and scleroderma nephropathy, which results are promising. Some reports suggest that the endothelin system might contribute to ischemia-reperfusion injury, acute graft rejection and deterioration of graft function. Endothelin inhibition in renal transplantation and its influence on graft survival is the future direction needing further research. The most frequent side effects associated with ETAR antagonists is fluid retention. Additionally, it should be considered if selective ETAR antagonists therapy needs to be co-administered with sodium-glucose co-transporter 2 inhibitors, renin-angiotensin-aldosterone inhibitors or diuretics and which patients should be recruited to such treatment to minimize the risk of adverse outcomes.

The Internalization Pathways of Liposomes, PLGA, and Magnetic Nanoparticles in Neutrophils.

Neutrophils are emerging as promising candidates for cell-based nanodrug delivery to tumors due to their unique biological properties. This study aims to investigate the mechanisms of nanoparticle internalization by neutrophils, specifically focusing on liposomes, poly(lactic-co-glycolic acid) (PLGA), and magnetite nanoparticles. Understanding these mechanisms could enhance the efficiency of neutrophil-based nanodrug delivery for cancer treatment. Neutrophils were isolated from the peripheral blood of mice bearing 4T1 mammary adenocarcinoma. Confocal microscopy, transmission electron microscopy, and flow cytometry were employed to evaluate the uptake of liposomes, PLGA, and magnetite nanoparticles by neutrophils. The effects of cultivation conditions, such as the presence or absence of plasma in the growth medium, were also examined. Additionally, the roles of immunoglobulins (IgG/IgM) and cell surface receptors (Fc and scavenger receptors) in nanoparticle internalization were explored. All types of nanoparticles were successfully internalized by neutrophils, though the mechanisms of uptake varied. Plasma presence in the medium significantly influenced nanoparticle binding, particularly for PLGA nanoparticles. Internalization of PLGA nanoparticles was found to depend on the presence of IgG/IgM in the medium and Fc receptors on neutrophil surfaces, while scavenger receptors were not involved. Understanding the distinct endocytosis pathways for different nanoparticles can improve the efficacy of neutrophil loading with nanodrugs, potentially advancing the development of neutrophil-based cancer therapies. The findings underscore the importance of the extracellular environment in modulating nanoparticle uptake.

Immunoglobulins: Mechanistic Approaches in Moderation of Various Inflammatory and Anti-Inflammatory Pathways.

Immunoglobulins (Ig) are proteins that help fight infections. IgG (IgG1, IgG2, IgG3, IgG4), IgM, IgA, IgD, and IgE are the five immunoglobulin subtypes that make up the majority of our immune system. Beneficial effects have been observed on the administration of Ig in diseases like Kawasaki, multiple myositis, chronic inflammatory demyelinating polyneuropathy (CIDP), and immune thrombocytopenia purpura (ITP). The Fc region, FcγRs, and FcRn of the IgG interact to provide both pro- and anti-inflammatory effects. IgM blocks immune-mediated inflammation using N-like glycans. It has been demonstrated that IgM demonstrates its antiinflammatory activity through IgM anti-leukocyte auto-antibodies (IgM-ALA). Since IgA is the second most prevalent and important Ig that operates on the primary objective in the immune system, which exhibits inhibitory signals in the body and generates inflammation in host cells, it plays a critical role in controlling mucosal homeostasis in the gastrointestinal (GI) tract. Additionally, it has been discovered that activating FcαRI boosts cytokine responses at different levels. IgD, a mysterious class of Ig once discovered, has a role in many disorders, including myeloma and Hodgkin's disease. The stability of IgD with development shows a different role, which has an advantage for the host's survival. IgE is mainly associated with many allergic diseases (food allergies), mediates type 1 responses, and has defenses against parasitic infections, which makes it an important parameter for monoclonal antibodies. Studies showed the possible roles of immunoglobulins, from which it came to light that immunoglobulins have their functions as agonists and antagonists in inflammation.

The role of immunoglobulin in cerebrospinal fluid on the differential diagnosis of autoimmune encephalitis and viral encephalitis in children

BackgroundA case-control study was conducted to analyze the role of cerebrospinal fluid immunoglobulin in the differential diagnosis of autoimmune encephalitis and viral encephalitis in children.MethodsOne hundred and twenty patients with autoimmune encephalitis (AE) treated in our hospital from February 2021 to February 2022 were included as the observation group (AE group). 100 patients with viral encephalitis (VE group) were selected as the control group. The clinical data of all patients were collected and analyzed retrospectively. Immunoglobulin G (IgG) and immunoglobulin A (IgA)in cerebrospinal fluid of the two patients were measured by immune turbidimetry. Immunoglobulin M (IgM), and the diagnostic value of immunoglobulin in cerebrospinal fluid (CSF) in patients with AE was analyzed by receiver working curve (ROC).ResultsThe level of IgG in the cerebrospinal fluid of the AE group was higher than that of the VE group, and the level of IgM was lower than that of the VE group, and the difference was statistically significant (P < 0.05). There was no significant difference in IgA levels between the two groups (P > 0.05). In terms of Magnetic Resonance (MR) features, the paraventricular, hippocampal, occipital and parietal lobes were more involved in AE patients, frontal and temporal lobes were more involved in VE patients, and paraventricular and occipital lobes were involved in MS. The proportion of bilateral extensive lesions in both groups was significantly higher than 50%. The proportions of patients in the AE group involving the lateral ventricle, insula, and parietal lobes were significantly higher than those in the VE group, and the proportions involving the basal ganglia, temporal lobes, and frontal lobes were significantly lower than those in the VE group, and the differences were statistically significant (All P < 0.05). The Area Under Curve (AUC) of IgG, IgA and IgM alone in the diagnosis of AE were 0.795(0.587–0.762), 0.602(0.502–0.631) and 0.627(0.534–0.708), respectively with the sensitivity values of 81.24% and 65.608, respectively and the specificity values of 65.08%, 57.54% and 75.01% respectively. The AUC of IgA + IgM in the diagnosis of AE was 0.733(0.617–0.849), and the sensitivity and specificity are 62.58% and 75.07% respectively. The AUC of IgA + IgG in the diagnosis of AE was 0.823(0.730–0.917), and the sensitivity and specificity were 81.24% and 67.54% respectively. The AUC of IgG + IgM in the diagnosis of AE was 0.886(0.814 ~ 0.958), and the sensitivity and specificity were 84.48% and 77.59% respectively. The AUC of IgA + IgM + IgG in the diagnosis of AE was 0.924 (0.868–0.981) with the sensitivity of 93.82%, and the specificity of 77.56%.ConclusionThe level of immunoglobulin in cerebrospinal fluid can be used as an effective reference index for the diagnosis of AE. The combined detection of IgA, IgM and IgG can improve the accuracy, sensitivity and specificity of AE.

Association of serum total IgE and allergen-specific IgE with insulin resistance in adolescents: an analysis of the NHANES database

BackgroundRecent studies have found that total immunoglobulin E (IgE) and allergen-specific IgE were associated with some metabolic diseases. However, the role of IgE in metabolism among adolescents is still unclear. Herein, this study aims to investigate the associations of serum total IgE and allergen-specific IgE with insulin resistance (IR) in adolescents, in order to provide some reference for the prevention and treatment of metabolic diseases in a young age.MethodsData of 870 adolescents were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 2005–2006 in this cross-sectional study. Weighted univariate and multivariate logistic regression analyses were utilized to screen covariates and explore the relationships of serum total IgE and allergen-specific IgE with IR. The evaluation indexes were odds ratios (ORs) and 95% confidence intervals (CIs). In addition, these relationships were also assessed in subgroups of allergy history, asthma history, and number of allergens.ResultsAmong eligible adolescents, 168 had IR. No significant association between serum total IgE level and IR was found. However, adolescents with higher level of allergen-specific IgE to rye grass [OR = 0.47, 95%CI: (0.25–0.91)], white oak [OR = 0.57, 95%CI: (0.37–0.88)], or peanut [OR = 0.38, 95%CI: (0.15–0.97)] seemed to have lower odds of IR, whereas those had higher level of shrimp-specific IgE [OR = 2.65, 95%CI: (1.21–5.84)] have increased odds of IR. In addition, these associations between allergen-specific IgE and IR were also discovered in adolescents who had allergy history or asthma history, or had different numbers of allergens.ConclusionPaying attention to different allergens in adolescents may be important in the early identification of IR among this high-risk population. The study results relatively provided some reference for further exploration on IR prevention.

Artificial intelligence-driven design of the assembled major cat allergen Fel d 1 to improve its spatial folding and IgE-reactivity

BackgroundCat-derived allergens are considered as one of the most common causes of allergic diseases worldwide. Fel d 1 is a major cat allergen and plays an important role in immunoglobulin E (IgE)-reaction diagnosis. However, the two separate chains of Fel d 1 exhibited lower IgE-reactivity than its complete molecule of an assembled form, which makes it difficult to efficiently prepare and limits the application of Fel d 1 in molecular diagnosis of cat allergy. MethodsWe first applied artificial intelligence (AI) based tool AlphaFold2 to build the 3-dimensional structures of Fel d 1 with different connection modes between two chains, which were evaluated by ERRAT program and were expressed in Escherichia coli. We then calculated the expression ratios of soluble form/inclusion bodies form of optimized Fel d 1. The Circular Dichroism (CD), High Performance Liquid Chromatography-Size Exclusion Chromatography (HPLC-SEC) and reducing/non-reducing SDS-PAGE were performed to characterize the folding status and dimerization of the optimized fusion Fel d 1. The improvement of specific-IgE reactivity to optimized fusion Fel d 1 was investigated by enzyme linked immunosorbent assay (ELISA). ResultsAmong several linkers, 2 × GGGGS got the highest scores, with an overall quality factor of 100. The error value of the residues around the junction of 2 × GGGGS was lower than others. It exhibited highest proportion of soluble protein than other Fel d 1 constructs with ERRAT (GGGGS, KK as well as direct fusion Fel d 1). The results of CD and HPLC-SEC showed the consistent folding and dimerization of two fused subunits between the optimized fusion Fel d 1 and previously well-defined direct fusion Fel d 1. The overall IgE-binding absorbance of optimized fusion Fel d 1 tested by ELISA was improved compared with that of the direct fusion Fel d 1. ConclusionWe firstly provided an AI-design strategy to optimize the Fel d 1, which could spontaneously fold into its native-like structure without additional refolding process or eukaryotic folding factors. The improved IgE-binding activity and simplified preparation method could greatly facilitate it to be a robust allergen material for molecular diagnosis of cat allergy.

Case of Autoimmune Haemolytic Anaemia (Aiha) in an Immunocompetent 1-Month-Old Child with Congenital Cytomegalovirus (cCMV) Infection

Here we report a case of congenital CMV infection with rare presentation as haemolytic anaemia in a 50-day-old infant. Clinical manifestations of our patient were pallor, jaundice, hepatosplenomegaly, and a deranged coagulation profile. Congenital CMV being the most common viral congenital infection should be suspected in every neonate and infant presenting with haemolytic anaemia. It is also the most common non-genetic cause of SNHL and not much is yet there for its prevention except for primary prevention as the role of immunoglobulin is still under trial.

MZB1-mediated IgA secretion suppresses the development and progression of colorectal cancer triggered by gut inflammation

Colorectal cancer (CRC) ranks among the top causes of mortality globally. Gut inflammation is one crucial risk factor that augments CRC development since patients suffering from inflammatory bowel disease have an increased incidence of CRC. The role of immunoglobulin (Ig)A in maintaining gut homeostasis and preventing inflammation has been well established. Our earlier work demonstrated that the marginal zone and B1 cell-specific protein (MZB1) promotes gut IgA secretion and its absence results in pronounced dextran sulfate sodium salt (DSS)-induced colitis. In the present study, we explored the role of MZB1 in CRC development using the azoxymethane (AOM)/DSS-induced CRC model. We observed an increase in both the number and size of the tumor nodules in Mzb1-/- mice compared with Mzb1+/+ mice. The increase in CRC development and progression in Mzb1-/- mice was associated with reduced intestinal IgA levels, altered gut flora, and more severe gut and systemic inflammation. Oral administration of the monoclonal IgA, W27, alleviated both the gut inflammation and AOM/DSS-induced CRC. Notably, cohousing Mzb1+/+ and Mzb1-/- mice from the 10th day after birth led to similar CRC development. Our findings underscore the pivotal role of MZB1-mediated IgA secretion in suppressing the onset and progression of CRC triggered by gut inflammation. Moreover, our study highlights the profound impact of microbiota composition, modulated by gut IgA levels, on gut inflammation. Nonetheless, establishing a direct correlation between the severity of colitis and subsequent CRC development and the presence or absence of a particular microbiota is challenging.

Necesidades no cubiertas en asma alérgica grave

Severe asthma affects 3%-10% of the world's population, according to estimates by the Global Initiative for ASTHMA (GINA). Allergic asthma is one of the most common phenotypes of severe asthma and it is characterized by allergen-induced type2 inflammation in which immunoglobulinE (IgE) is a key mediator, making it an important therapeutic target. The introduction of targeted biological therapies or treatments has entered the management for severe asthma in the era of precision medicine, and the goal of treatment is clinical remission of the disease. There is a significant percentage of patients with severe allergic asthma who do not respond to treatments and whose symptoms are not controlled. In this paper, a group of experts in the management of severe allergic asthma reviewed and evaluated the most relevant evidence regarding the pathophysiology and phenotypes of severe allergic asthma, the role of IgE in allergic inflammation, allergen identification, techniques, biomarkers and diagnostic challenges, available treatments and strategies for disease management, with a special focus on biological treatments. From this review, recommendations were developed and validated through a Delphi consensus process with the aim of offering improvements in the management of severe allergic asthma to the professionals involved and identifying the unmet needs in the management of this pathology.

A Bibliometric Analysis of Global Research on Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are a clinical syndrome characterized by the abrupt onset of major personality, movement, and behavioral changes in a patient with a history of streptococcal infection. We aimed to do a bibliometric analysis of the published research on PANDAS. All the published articles available on the PubMed database from the time of inception till August 2022 were included in the study. All the PubMed IDs (PMID) of the articles were entered in Harvard Catalyst, a free online software, for bibliometric analysis, and data were extracted and verified. A total of 289 relevant published articles were identified. The average number of authors per article was 4.89 and the average number of times an article was cited was 11.19 (excluding self-citation). The H-index of the published articles was 31. The Journal of Child and Adolescent Psychopharmacology published the maximum number of articles ( n = 36). The highest number of average citations (39.50 citations/articles) was for the articles published in the American Journal of Psychiatry. The most common type of articles were journal articles ( n = 259) and of which 27 were original research articles. Most of the original research discusses the effectiveness of various interventions (penicillin and other antibiotic prophylaxis, role of immunoglobulin), neuropsychiatric symptoms, and outcomes in the longitudinal course. Though PANDAS is a well-researched entity, more clinical trials, and large-scale studies will help provide better insight on this subject.

Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Sibeprenlimab in Healthy Participants.

Sibeprenlimab blocks the cytokine "A Proliferation-Inducing Ligand" (APRIL), which may play a key role in immunoglobulin A nephropathy pathogenesis. A phase 1 study of subcutaneous (SC) sibeprenlimab evaluated preliminary safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy participants. This was an open-label, single-ascending-dose study. Twelve participants in each of 4 sequential dosing cohorts received 1 SC dose of sibeprenlimab (200mg [1×1mL injection], 400mg [2×1mL injections], 400mg [1×2mL injection], or 600mg [1 mL+2mL injections]) and underwent 16-week follow-up for adverse events, pharmacokinetics, and pharmacodynamics (serum APRIL, immunoglobulin [Ig] levels). Sibeprenlimab in single SC doses of 200-600mg was slowly absorbed into the systemic circulation, with a median time to maximum serum concentration of approximately 6-10.5 days, and a mean elimination half-life of approximately 8-10 days. Serum APRIL, IgA, IgM, and, to a lesser extent, IgG decreased in a dose-dependent and reversible manner. Maximal reduction in serum IgA was approximately 60% at the 400- and 600-mg doses and 40% at 200mg. Serum APRIL rapidly decreased to near the lower limit of quantification, and duration of suppression was dose-dependent, with near complete suppression until weeks 4-6 at the 400-mg dose and week 8 at the 600-mg dose. Adverse events occurred in 30/48 (62.5%) participants; none were serious or led to study discontinuation. Sibeprenlimab rapidly and sustainably reduced target APRIL and Ig biomarkers in a dose-dependent and reversible manner, with acceptable preliminary safety and pharmacokinetics.

P-505 Role of intramuscular immunoglobulin in improving the live birth rate in ANA positive women with recurrent pregnancy loss

Abstract Study question In ANA positive women with Recurrent Pregnancy Loss, could addition of intramuscular Immunoglobulin along with appropriate adjuvant therapy improve the live birth rate ? Summary answer In ANA positive RPL patients, addition of Intramuscular immunoglobulin along with glucocorticoids and low dose aspirin improves the live birth rate What is known already RPL is a frustrating condition which affects 1-3% of women trying to conceive. Presence of ANA is associated with autoimmunity, which affects trophoblast development and vascular remodeling process thereby resulting in pregnancy loss. Latest ESHRE guidelines also suggest ANA testing for explanatory purpose. Aspirin has anti-platelet and anti-inflammatory effects, and glucocorticoids exhibit a beneficial effect in autoimmune diseases. Therefore, they are considered conventional adjuvant therapies in ANA-positive women with RPL. Addition of Immunoglobulin for RPL patients benefits by the down-regulation of primary antibody production, the modulation of complement activation and Suppresses Nk cell cytotoxicity Study design, size, duration 72 ANA positive patients with Unexplained RPL were enrolled in the study. Anatomical, metabolic ,genetic and other immunological causes for RPL were excluded. Out of 72 patients 36 patients were allotted to the treatment group, who received intramuscular immunoglobulins along with Low dose aspirin and glucocorticoids, remaining 36 patients were allotted to the control group, who received only Aspirin and glucocorticoids. Duration of study extended from jan2021 till Dec 2022 Participants/materials, setting, methods 72 patients with unexplained RPL underwent ANA screening using Indirect Immunofluorescence technique in the pre conception period. Patients with a titre ≥1:80 were considered to be significant and enrolled in the study. Patients were allotted to the Treatment and Control group based on personal choice of the patient after informed consent. Live birth rate was the primary outcome analyzed. Main results and the role of chance There were no significant differences in socio-demographic characteristics between group. Patient characteristics – Age, BMI, Ovarian reserve, sperm factor and number of previous Pregnancy losses were matched.Treatment group who received Intramuscular immunoglobulin once in 3 weeks right from the time of positive pregnancy test till 28 weeks along with low dose aspirin and glucocorticoids had a live birth rate of (23/36 ) 63.8 % whereas Control group who received only Low dose Aspirin (75 mg) and Glucocorticoids had a live birth rate of 41.6 % (15/36). Other obstetric outcomes which were analysed were Pre Eclampsia and GDM which were comparable between both the groups.Preterm labour was marginally higher in the control group. Limitations, reasons for caution Because of limited sample size results need to be interpreted with caution. Screening for ANA antibodies in patients were done only preconceptionally, and we were not aware about their ANA titres in pregnancy. This study involves only patients who conceived with IVF treatment and doesn't include spontaneous natural conception Wider implications of the findings ANA screening in RPL cases is suggested to prognosticate the outcome. Addition of Immunoglobulins significantly increases the live birth rate in these cases. Role of Immunoglobulin in patients with altered cellular immunity has to be further studied which is likely to benefit other cases of unexplained RPL. Trial registration number not applicable

Targeting the Alternative Complement Pathway With Iptacopan to Treat IgA Nephropathy: Design and Rationale of the APPLAUSE-IgAN Study

Targeting the alternative complement pathway (AP) is an attractive therapeutic strategy because of its role in immunoglobulin A nephropathy (IgAN) pathophysiology. Iptacopan (LNP023), a proximal complement inhibitor that specifically binds to factor B and inhibits the AP, reduced proteinuria and attenuated AP activation in a Phase 2 study of patients with IgAN, thereby supporting the rationale for its evaluation in a Phase 3 study. APPLAUSE-IgAN (NCT04578834) is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 study enrolling approximately 450 adult patients (aged≥18 years) with biopsy-confirmed primary IgAN at high risk of progression to kidney failure despite optimal supportive treatment. Eligible patients receiving stable and maximally tolerated doses of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) will be randomized 1:1 to either iptacopan 200 mg or placebo twice daily for a 24-month treatment period. A prespecified interim analysis (IA) will be performed when approximately 250 patients from the main study population complete the 9-month visit. The primary objective is to demonstrate superiority of iptacopan over placebo in reducing 24-hour urine protein-to-creatinine ratio (UPCR) at the IA and demonstrate the superiority of iptacopan over placebo in slowing the rate of estimated glomerular filtration rate (eGFR) decline (total eGFR slope) estimated over 24 months at study completion. The effect of iptacopan on patient-reported outcomes, safety, and tolerability will be evaluated as secondary outcomes. APPLAUSE-IgAN will evaluate the benefits and safety of iptacopan, a novel targeted therapy for IgAN, in reducing complement-mediated kidney damage and thus slowing or preventing disease progression.

Role of IgG food test in patients with allergic diseases

&lt;abstract&gt; &lt;p&gt;The role of immunoglobulin G (IgG) food elimination in allergic diseases is controversial. This main aim is to clarify the beneficial effects of specific immunoglobulin G (sIgG) food elimination on improving allergic diseases. International guidelines disagree about the beneficial roles of IgG food elimination on allergic diseases. However, many studies have proven the role of IgG food elimination on allergic diseases. In atopic dermatitis children, studies have shown that milk, egg, wheat, and soya are positive for sIgGs and there sIgG elimination will improve atopic dermatitis. In allergic rhinitis, the sIgG4 food test is usually positive to seafood, and IgG food elimination will improve both allergic rhinitis and asthma symptoms. In asthma, persistent IgE egg sensitizers have higher sIgG1 to egg than partial IgE egg sensitizers. Additionally, high sIgG1 to egg is a risk factor for future asthma (with sensitivity of 64% and specificity of 74%). In asthma, persistent sIgG1 egg sensitization is risk for future asthma and IgG food elimination will improve asthma (especially milk and egg). In chronic urticaria, the most common positive sIgGs to food are cola nut, yeast, wheat, red kidney bean, pea, corn, and egg white in Saudi Arabia. Women and patient aged &amp;lt; 40 years have higher positive sIgG rates to several foods. In food intolerance, IgG food elimination will improve the symptoms of food intolerance. Furthermore, primary prevention of food intolerance can be achieved by early IgG food elimination. In conclusion, despite those most international guidelines disagree about the beneficial role of IgG food elimination on allergic diseases; some studies support its role. This test may be used if patients' symptoms do not improve after the IgE food tests. Moreover, IgG food companies should offer cheap short lists, such as ImuPro Screen 22 foods or ImuPro Screen Plus 44 foods.&lt;/p&gt; &lt;/abstract&gt;

Elevation of IgE in patients with psoriasis: Is it a paradoxical phenomenon?

Immunoglobulin E (IgE) elevation is a hallmark of allergic conditions such as atopic dermatitis (AD). The pathogenesis of AD is typically associated with high levels of IL-4 and IL-13 produced by activated T helper 2 (Th2) cells. Psoriasis, on the other hand, is an inflammatory skin disease mainly driven by Th17 cells and their related cytokines. Although the immunopathologic reactions and clinical manifestations are often easily distinguished in the two skin conditions, patients with psoriasis may sometimes exhibit AD-like manifestations, such as elevated IgE and persistent pruritic lesions. Given the fact that the effective T cells have great plasticity to re-differentiate in response to innate and environmental factors, this unusual skin condition could be a consequence of a cross-reaction between distinct arms of T-cell and humoral immunity. Here we review the literature concerning the roles of IgE in the development of AD and psoriasis, showing that elevated IgE seems to be an important indicator for this non-typical psoriasis.

The Role of Immunoglobulin G (IgG), IgA and IgE-Antibodies against Helicobacter pylori in the Development of Oxidative Stress in Patients with Chronic Gastritis.

Aim: To study the predominant serum responses (antibodies IgG, IgA, IgE) against H. pylori in relation to the indicators of the system “lipid peroxidation–antioxidant system” in various pathogenetic variants of chronic gastritis (CG). Materials and Methods: Sixty patients with CG, 33 patients with chronic atrophic gastritis (CAG) and 31 patients with chronic allergic gastritis (CALG) were examined. The values of the system of lipid peroxidation and antioxidant protection in plasma were determined in the serum of patients using a spectrophotometric method. Statistical data processing was carried out using the Statistica 7.0 software package (StatSoft, Tulsa, OK, USA). Results: With serum responses “antibodies IgG > IgA” and “high concentrations of IgE antibodies”, we found unidirectional changes in the form of an increase in the amount of diene conjugates, malondialdehyde and an increase in the activity of all enzymes: superoxide dismutase, catalase, glutathione-S-transferase and glutathione peroxidase. With a serum response with low concentrations of IgG, IgA antibodies, multidirectional changes were found in the form of an increase in the amount of diene conjugates, malondialdehyde and a decrease in the activity of all enzymes: superoxide dismutase, catalase, glutathione-S-transferase and glutathione peroxidase relative to the control group. Conclusions: The obtained data testify to the balance of lipid peroxidation and antioxidant system processes and depend on the characteristics of the immune response to H. pylori infection.

MO154: Enteric Budesonide in IGAN Nephropathy: A Real World Clinical Practice

Abstract BACKGROUND AND AIMS The gut–kidney axis seems to have a principal role in immunoglobulin A nephropathy (IgAN) development [1], leading to new treatment approaches. Enteric budesonide, a glucocorticosteroid that release the active drug in the distal ileum, has proved proteinuria reduction and estimated glomerular filtration rate (eGFR) benefit [1, 2]. Moreover, systemic steroid therapy implies severe adverse events that budesonide seems to avoid [1, 3]. Therefore, we aim to evaluate the effect of budesonide treatment in our cohort of patients affected by IgAN. METHOD We retrospectively selected 17 patients, from 19 to 74 years, which were treated with enteric budesonide. All of them, except for a patient with Henoch-Schönlein purpura and microhaematuria, had a renal biopsy-confirmed primary IgAN. Twelve were patients with native kidney disease and five were patients with kidney transplant. Three with native kidney disease were excluded due to the lack of therapeutic compliance. The median dose of budesonide was 9 mg/day for the whole period of treatment. Twelve were already treated with renin-angiotensin system (RAS) blockade, which was continued throughout the follow-up period. During the follow-up (maximum 2 years), creatinine, proteinuria measured as change in urine protein creatinine ratio (UPCR) and haematuria were assessed. RESULTS Baseline characteristics are shown in Table 1. Overall, the median reductions of UPCR at 3, 6, 12 and 24 months were of 33.08%, 54.62%, 15.38% and 15.38%, respectively. At 6 months, the median UPCR was reduced from baseline 1.3 g/g [IQ range (25%–75%): –0.58 to –4.22] to 0.59 g/g [IQ range (25%–75%): –0.17 to –0.85], P = .028. The creatinine remained stable at 6 months, with baseline median 1.57 mg/dL [IQ range (25%–75%): –1.03 to to 2.03], and creatinine at 6 months with median 1.42 mg/dL [IQ range (25%–75%): –1.01 to –1.93]. Five patients (35.7%) did not have haematuria when budesonide was started, which remained stable at 6 months. No corticosteroid-related side effects were observed. No differences were found between patients with native disease or transplant kidney. CONCLUSION Enteric budesonide reduced proteinuria in patients with IgAN nephropathy. Our results suggest that enteric budesonide may represent a new approach to treatment of IgAN in both patients with native and kidney transplant.

AllergoOncology: Role of immune cells and immune proteins.

BackgroundImmune cells and immune proteins play a pivotal role in host responses to pathogens, allergens and cancer. Understanding the crosstalk between allergic response and cancer, immune surveillance, immunomodulation, role of immunoglobulin E (IgE)‐mediated functions and help to develop novel therapeutic strategies. Allergy and oncology show two opposite scenarios: whereas immune tolerance is desired in allergy, it is detrimental in cancer.AimThe current review provides an update on the role of immune cells and immune proteins in allergy and cancer fields.MethodsAuthors investigated the role of relevant immunological markers and the correlation with cancer progression or cancer suppression.ResultsActivated immune cells such as macrophages ‘M1’, dendritic cells (DCs), innate lymphoid cells (ILC2), NK cells, Th1, follicular T helper cells (TFH), TCD8+, B lymphocytes and eosinophils have inhibitory effects on tumourigenesis, while tolerogenic cells such as macrophages ‘M2,’ tolerogenic DCs, ILC3, T and B regulatory lymphocytes appear to favour carcinogenesis. Mastocytes and alarmins can have both effects. RIgE antibodies and CCCL5 chemokine have an anticancer role, whereas IgG4, free light chains, Il‐10, TGF‐β, lipocalin‐2, CCL1 chemokine promote cancer progression. Fundamental is also the contribution of epigenetic changes regulated by the microRNA in cancer progression.ConclusionThis knowledge represents the key to developing new anticancer therapies.

The role of immunoglobulin E and mast cells in hypertension.

Hypertension is the major cause of cardiovascular diseases and global mortality. Immunoglobulin E (IgE), which plays crucial roles in allergic diseases, has been implicated in the pathogenesis of vascular and cardiac remodelling via its receptor (FcεR1). In this study, we aimed to reveal the role of IgE and FcεR1 in hypertension. Herein, we reported that IgE levels were significantly increased in hypertensive patients as well as in hypertensive mice induced by angiotensin II (Ang II). Ang II-induced vascular remodelling and hypertension were significantly alleviated in FcεR1 genetic knockout mice or in mice treated with anti-IgE monoclonal antibody. Similarly, treatment with omalizumab (a clinical IgE antagonist) also markedly inhibited Ang II-induced hypertension. Furthermore, the cellular contribution of IgE-FcεR1 in hypertension was evaluated in mice with FcεR1 conditional knockout in mast cell (MC), smooth muscle cell (SMC), or endothelial cell (EC). Our data revealed that IgE-mediated hypertension is largely dependent on FcεR1 in MCs but not SMCs and ECs. Finally, RNA-seq and signalling pathway analyses of mouse bone marrow-derived MCs suggested that interleukin 6 (IL-6) is one of critical mediators in IgE-mediated hypertension. IL-6 derived from IgE-stimulated MCs promoted reactive oxygen species production and decreased the levels of phosphorylated endothelial nitric oxide synthase in ECs, leading to endothelial dysfunction. Our findings reveal that IgE contributes to the pathogenesis of hypertension, at least partially through activating the IgE-FcεR1 signalling in MCs. Thus, IgE may represent a new therapeutic target for IgE-mediated hypertension.

Malignancy risk in pediatric subjects with undetectable serum IgE

Immunoglobulin E (IgE) is a key mediator in Type I hypersensitivity reactions, and may also be involved in the immune response to parasitic infections. A possible role for IgE in tumor immunosurveillance has been proposed, and IgE deficiency has been associated with an increased risk for various malignancies in adult subjects. However, the association between IgE deficiency and cancer has not been addressed in pediatric populations. We hypothesized that absent serum IgE (< 3 IU/mL) in children could be associated with a higher risk for malignancy.