Publications by authors named "Prussin C"

Article Synopsis
  • - A study was conducted to test dexpramipexole, a new oral drug aimed at reducing eosinophils in patients with eosinophilic asthma, to see if it is safe and effective.
  • - In a trial involving 103 participants, those taking dexpramipexole (especially the 150 mg and 75 mg doses) showed significant reductions in eosinophil levels compared to the placebo group and maintained a good safety profile.
  • - The results indicate that dexpramipexole effectively lowers eosinophils, but more extensive studies are needed to evaluate its overall impact on asthma outcomes.
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  • This study investigates the reliability of measuring eosinophil granule proteins in blood and urine to better assess disease activity in eosinophil-related disorders treated with novel therapies like mepolizumab and benralizumab.
  • While urine eosinophil-derived neurotoxin (uEDN) levels increased during clinical relapse, plasma levels were more variable and correlated with absolute eosinophil counts and prednisone dosage, indicating that uEDN may serve as a noninvasive biomarker.
  • Findings suggest that measuring eosinophil granule proteins, especially in urine, could improve the understanding of disease activity in conditions like hypereosinophilic syndrome (HES) and eos
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  • - The study investigated the oral drug dexpramipexole for treating chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilia, finding it significantly lowered eosinophil counts in patients over six months.
  • - Out of 16 subjects, 13 completed the treatment, showing a 94% reduction in blood eosinophils and a 97% reduction in tissue eosinophils, although there was no significant decrease in nasal polyp scores or other clinical symptoms.
  • - The treatment was well tolerated, with no severe side effects reported, indicating that while eosinophil levels dropped dramatically, it did not translate into symptom relief for the patients.
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  • Hypereosinophilic syndromes (HESs) involve a high eosinophil count in the blood and damage to organs, typically treated with glucocorticoids (GC), but high doses can cause side effects.
  • A study tested dexpramipexole, a drug shown to reduce eosinophil counts safely in an ALS trial, as a potential GC-sparing treatment for HESs, giving 150 mg twice daily to participants.
  • Results showed 40% of subjects had more than a 50% decrease in their necessary GC dose, and tissue biopsies revealed fewer eosinophils, suggesting dexpramipexole could effectively lower GC use without serious side effects, although
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  • Eosinophil-associated diseases (EADs) are rare disorders marked by the presence of eosinophils in tissues and blood, leading to various health issues, but research faces challenges in models and methods.
  • A review of eosinophil research since 2012 highlighted gaps in basic and clinical studies, emphasizing the need for better understanding of eosinophil biology, phenotypes, and biomarkers.
  • The need for improved tools in clinical trials, including better scoring systems and patient-reported outcomes, was stressed to enhance research collaboration and drug development in the field.
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  • Th2 cells are essential for the development of eosinophil-driven type 2 inflammation caused by allergens.
  • Recent research highlights a subset of Th2 cells, called pathogenic effector Th2 (peTh2) cells, that have stronger disease-causing abilities compared to typical Th2 cells.
  • The article reviews the characteristics and functions of peTh2 cells in both animal studies and human cases, focusing on their potential as a target for treating allergic eosinophilic inflammation.
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  • Neoplastic accumulation of mast cells in systemic mastocytosis (SM) is linked to activating mutations in the KIT receptor, which can affect redox balance in the body.
  • The study found that reactive oxygen species (ROS) levels increased in both indolent and aggressive forms of SM, while DJ-1 protein levels showed a complex response based on the severity of the disease and mast cell burden.
  • The research suggests that targeting IL-6 may be a promising therapy for advanced mastocytosis, as it could reduce DJ-1 levels and make the cancerous mast cells more susceptible to oxidative damage.
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  • Biomarkers are increasingly utilized in both research and clinical settings to diagnose diseases, predict their progression, and track treatment responses.
  • This review focuses on biomarkers related to mast cells, basophils, and eosinophils, which are key players in allergic inflammation.
  • The study highlights specific surface markers and products from these cells that could aid in clinical research and improve decision-making in allergy-immunology practices.
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Background: IL-6, levels of which are reported to be increased in association with mastocytosis, asthma, and urticaria, is used in conjunction with stem cell factor to generate CD34(+) cell-derived primary human mast cell (HuMC) cultures. Despite these associations, the effects on and mechanisms by which prolonged exposure to IL-6 alters HuMC numbers and function are not well understood.

Objectives: We sought to study the effect of IL-6 on HuMC function, the mechanisms by which IL-6 exerts its effects, and the relationship of these findings to mastocytosis.

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Article Synopsis
  • IL-5(+) pathogenic effector T(H)2 cells (peT(H)2) are a specific subpopulation of T(H)2 cells known for their strong pro-inflammatory functions, previously studied mainly in mouse models of allergies.
  • The research aimed to identify specific markers for human peT(H)2 cells and to explore their role in allergic eosinophilic disorders, involving patients with eosinophilic gastrointestinal disease and atopic dermatitis.
  • Findings revealed that peT(H)2 cells have distinct markers and produce higher levels of cytokines IL-5 and IL-13, and are significantly more abundant in patients with allergic conditions compared to healthy individuals, suggesting their key role in allergic inflammation.
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  • Intracellular cytokine staining (ICCS) is a cutting-edge technique that uses fluorescent antibodies and flow cytometry to study cytokine expression in individual cells.* -
  • Recent improvements in flow cytometry allow ICCS to measure multiple cytokines at once, revealing complex cellular responses and enabling simultaneous analysis of other important cellular markers.* -
  • The protocol includes steps for stimulating cells in the lab, fixing them for analysis, and staining cell surfaces, making ICCS a powerful method compared to older techniques like ELISPOT and T cell cloning.*
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  • A new multiplex suspension array system was developed to measure major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil derived neurotoxin (EDN), and eosinophil peroxidase (EPO) simultaneously in serum, addressing previous measurement inefficiencies.
  • The assay demonstrated high reliability and correlation with traditional ELISA methods while requiring significantly less serum for effective sensitivity.
  • It identified increased concentrations of eosinophil proteins in subjects with eosinophilic gastrointestinal disorders, indicating its potential for assessing eosinophilic disease severity.
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Article Synopsis
  • - Eosinophilic gastroenteritis (EGE) is part of a group of conditions called eosinophilic gastrointestinal disorders, which includes other types like eosinophilic esophagitis (EoE) and gastroenteritis.
  • - EGE symptoms can vary widely, ranging from nausea and vomiting to serious issues like protein loss or bowel obstruction that might need surgery.
  • - While systemic corticosteroids effectively treat EGE, they can cause significant side effects, highlighting the urgent need for better treatment options.
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Article Synopsis
  • ATRA, a form of vitamin A, enhances Th2 cytokine responses through its receptor RARα, affecting two human Th2 cell subpopulations differently: IL-5- Th2 and IL-5+ Th2.
  • In experiments, ATRA increased the production and proliferation of IL-5+ Th2 cells specifically in response to allergens, while the RARα antagonist Ro415253 decreased their output.
  • The study indicates that targeting RARα could be a therapeutic strategy for managing allergic inflammation, as its effects are mostly seen in the highly differentiated IL-5+ Th2 cells.
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  • - Hypereosinophilic syndromes (HESs) are chronic conditions where excess eosinophils (a type of white blood cell) cause various health issues and can be life-threatening.
  • - Existing treatments, like imatinib, have helped improve patient outcomes, but there's a need for more effective and safer treatment options.
  • - This review discusses eosinophil biology and highlights possible new drug targets and treatments that are currently being researched or used for other diseases.
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  • - X-linked hyper-IgM syndrome (XHM) is an immune deficiency due to mutations in the CD40 ligand, and researchers tested a CD40 agonist antibody, CP-870,893, on two patients with biliary Cryptosporidiosis.
  • - CP-870,893 successfully activated B cells and other immune cells in the lab, and when used on patients, it reduced white blood cell levels in their blood and decreased stool shedding of the parasite.
  • - Although initial results were promising, including T cell activation, issues arose as patients' immune responses and oocyst shedding returned after stopping the treatment, suggesting further research into CD40 agonists like CP-870,893 is needed for XHM patients
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  • The study explores the functions of Th2 cytokine genes IL-4, IL-5, and IL-13, proposing that Th2 cells have distinct subpopulations based on cytokine expression and immune functions.
  • Researchers identified two main Th2 subpopulations: a minority IL-5(+) group (20% of Th2 cells) and a majority IL-5(-) group, with differences in differentiation, memory characteristics, and cytokine production.
  • The findings reveal that IL-5(+) Th2 cells are more differentiated and have specific epigenetic changes that enhance IL-5 expression, suggesting these subpopulations may have varying contributions to immune responses and related diseases.
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  • The study investigated the effects of anti-IgE therapy on allergen-specific T cell responses in patients with food sensitization, focusing on its role in inhibiting Th2 cell activation linked to allergens.* -
  • Nine subjects participated in a 16-week trial using omalizumab, and results showed that most had strong food allergen-specific T cell responses, primarily from CD4 T cells, with a notable Th2 inclination.* -
  • Contrary to initial expectations, the therapy did not significantly reduce any measures of T cell response, suggesting that IgE might not have a major role in promoting allergen presentation as previously thought.*
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T(H)2 immune responses are required for the 2 fundamental pathological processes characteristic of allergic disease: IgE-mediated hypersensitivity and eosinophilic inflammation. The 3 established T(H)2 cytokines, IL-4, IL-5, and IL-13, each play a nonredundant role in allergic disease pathology. The recent explosion of T(H) subpopulations combined with the wide availability of polychromatic cytokine staining has facilitated the discovery of T(H)2 lineage heterogeneity.

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Article Synopsis
  • - IgE plays a crucial role in allergic reactions by binding to receptors on mast cells and basophils, which helps initiate and sustain hypersensitivity responses
  • - Mast cells, basophils, and eosinophils are key players in both allergic inflammation and the immune system's responses to pathogens
  • - The review discusses the roles of these immune components in the development of allergic diseases and how they contribute to the overall inflammatory process
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  • Both anaphylactic food allergy and eosinophil-associated gastrointestinal disorders showcase different clinical features but are linked by T(H)2 immune responses and food-specific IgE levels.
  • The study found two distinct subpopulations of T(H)2 cells: IL-5+ T(H)2 cells were much more prevalent in allergic eosinophilic gastroenteritis (AEG) compared to peanut allergy (PA), indicating a different immune response pattern.
  • The findings suggest that T(H)2 responses are not uniform; IL-5+ T(H)2 cells are primarily reliant on AEG, while IL-5(-) T(H)2 responses correlate stronger with peanut allergy, highlighting a divergence in immunopathology between the two
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