Eosinophil-mast cell interaction: Mepolizumab leads to a reduction of clinical symptoms and serum tryptase in a patient with eosinophilic asthma and idiopathic mast cell activation

Guillet, Carole; Steinmann, Simona; Lang, Claudia; Maul, Julia‐Tatjana; Schmid‐Grendelmeier, Peter

doi:10.1016/j.jaip.2020.10.020

Cited by 7 publications

(3 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although we did not detect significant effects of benralizumab treatment on other cell types in nasal polyp tissue, the observed trend toward reduced mast cell counts is consistent with prior findings of mast cell reductions in patients with asthma and eosinophilic esophagitis when IL‐5 was inhibited with mepolizumab 32,33 . A reduction in mast cells is also consistent with the downregulation of mast cell gene signatures reported for patients with asthma following treatment with benralizumab 34 .…”

Section: Discussionsupporting

confidence: 89%

Pharmacokinetics/pharmacodynamics of benralizumab in chronic rhinosinusitis with nasal polyps: Phase III, randomized, placebo‐controlled OSTRO trial

Emson,

Han,

Hopkins

et al. 2024

Brit J Clinical Pharma

View full text Add to dashboard Cite

AimsBenralizumab, a humanized, afucosylated monoclonal antibody against the interleukin 5 receptor, α subunit, causes rapid depletion of eosinophils by antibody‐dependent cellular cytotoxicity. We investigated the pharmacokinetic and pharmacodynamic effects of benralizumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) from the phase III OSTRO trial.MethodsPatients received a placebo or 30 mg of benralizumab by subcutaneous injection every 8 weeks (first three doses every 4 weeks) to week 48; a subset of patients continued in an extended follow‐up period to assess treatment durability to week 80. Serum benralizumab concentrations and blood eosinophil and basophil counts were assessed to week 80. Biomarker assessments were performed on nasal polyp tissue biopsies at week 56 and nasal lining fluid at weeks 24 and 56 to examine changes in immune cells and inflammatory mediators.ResultsAmong 185 patients in this analysis, 93 received benralizumab. Serum benralizumab concentrations reached a steady state by week 24 (median concentration 385.52 ng mL−1); blood eosinophils were almost fully depleted and blood basophils were reduced between weeks 16 and 56. Nasal polyp tissue eosinophils decreased with benralizumab from 57.6 cells mm−2 at baseline to 0 cells mm−2 at week 56 (P < .001 vs placebo), and tissue mast cells were numerically reduced. In nasal lining fluid, eosinophil‐derived neurotoxin was significantly reduced at weeks 24 and 56 (P < .001) and interleukin‐17 at week 56 (P < .05) with benralizumab.ConclusionBenralizumab treatment led to rapid, sustained, nearly complete depletion of eosinophils from blood and nasal polyp tissue in patients with CRSwNP.

show abstract

Section: Discussionsupporting

confidence: 89%

Pharmacokinetics/pharmacodynamics of benralizumab in chronic rhinosinusitis with nasal polyps: Phase III, randomized, placebo‐controlled OSTRO trial

Emson,

Han,

Hopkins

et al. 2024

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…It is possibly explained either by the reduced number of eosinophils, which indirectly affects or diminishes the crosstalk of cells and hence lowers the production of basophils, or by the removal of IL-5 may directly, as basophils express the IL-5Ra [ 24 , 25 , 26 , 27 ]. Moreover, a human patient with eosinophilic asthma and an idiopathic mastocytosis receiving mepolozumab showed an eosinophil reduction and surprisingly a parallel significant reduction of mast cell-derived tryptase, strongly linked to mepolizumab applications, thus, further suggesting an eosinophil-mast cell interaction controlled by IL-5 [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Eosinophils Play a Surprising Leading Role in Recurrent Urticaria in Horses

Birkmann,

Jebbawi,

Waldern

et al. 2024

Vaccines

Self Cite

View full text Add to dashboard Cite

Urticaria, independent of or associated with allergies, is commonly seen in horses and often shows a high reoccurrence rate. Managing these horses is discouraging, and efficient treatment options are lacking. Due to an incidental finding in a study on horses affected by insect bite hypersensitivity using the eosinophil-targeting eIL-5-CuMV-TT vaccine, we observed the prevention of reoccurring seasonal urticaria in four subsequent years with re-vaccination. In an exploratory case series of horses affected with non-seasonal urticaria, we aimed to investigate the role of eosinophils in urticaria. Skin punch biopsies for histology and qPCR of eosinophil associated genes were performed. Further, two severe, non-seasonal, recurrent urticaria-affected horses were vaccinated using eIL-5-CuMV-TT, and urticaria flare-up was followed up with re-vaccination for several years. Eotaxin-2, eotaxin-3, IL-5, CCR5, and CXCL10 showed high sensitivity and specificity for urticarial lesions, while eosinophils were present in 50% of histological tissue sections. The eIL-5-CuMV-TT vaccine reduced eosinophil counts in blood, cleared clinical signs of urticaria, and even prevented new episodes of urticaria in horses with non-seasonal recurrent urticaria. This indicates that eosinophils play a leading role in urticaria in horses, and targeting eosinophils offers an attractive new treatment option, replacing the use of corticosteroids.

show abstract

“…The elevated mast cell tryptase levels in severe asthma patients suggest its importance, especially when combined with TSLP and blood eosinophil count, in linking to exacerbation risks. Mepolizumab significantly decreases the serum tryptase levels in patients with eosinophilic asthma and idiopathic mast cell activation syndrome [ 99 ]. Similarly, IL-13, along with biomarkers like periostin, blood eosinophils, and FeNO, is significantly higher in eosinophilic asthmatics [ 100 ].…”

Section: Diagnostic Biomarkers For Eosinophilic Asthmamentioning

confidence: 99%

Eosinophilic Asthma: Pathophysiology and Therapeutic Horizons

Hussain,

Liu

2024

Cells

View full text Add to dashboard Cite

Asthma is a prevalent chronic non-communicable disease, affecting approximately 300 million people worldwide. It is characterized by significant airway inflammation, hyperresponsiveness, obstruction, and remodeling. Eosinophilic asthma, a subtype of asthma, involves the accumulation of eosinophils in the airways. These eosinophils release mediators and cytokines, contributing to severe airway inflammation and tissue damage. Emerging evidence suggests that targeting eosinophils could reduce airway remodeling and slow the progression of asthma. To achieve this, it is essential to understand the immunopathology of asthma, identify specific eosinophil-associated biomarkers, and categorize patients more accurately based on the clinical characteristics (phenotypes) and underlying pathobiological mechanisms (endotypes). This review delves into the role of eosinophils in exacerbating severe asthma, exploring various phenotypes and endotypes, as well as biomarkers. It also examines the current and emerging biological agents that target eosinophils in eosinophilic asthma. By focusing on these aspects, both researchers and clinicians can advance the development of targeted therapies to combat eosinophilic pathology in severe asthma.

show abstract

Eosinophil-mast cell interaction: Mepolizumab leads to a reduction of clinical symptoms and serum tryptase in a patient with eosinophilic asthma and idiopathic mast cell activation

Cited by 7 publications

References 9 publications

Pharmacokinetics/pharmacodynamics of benralizumab in chronic rhinosinusitis with nasal polyps: Phase III, randomized, placebo‐controlled OSTRO trial

Pharmacokinetics/pharmacodynamics of benralizumab in chronic rhinosinusitis with nasal polyps: Phase III, randomized, placebo‐controlled OSTRO trial

Eosinophils Play a Surprising Leading Role in Recurrent Urticaria in Horses

Eosinophilic Asthma: Pathophysiology and Therapeutic Horizons

Contact Info

Product

Resources

About