Interaction Between Benralizumab and Basophils in Eosinophilic Asthma

Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz20 enrolled

Overview

In this study, investigators want to evaluation of the impact of benralizumab (Fasenra®, Astra Zeneca) on different cell populations, including basophils and innate lymphoid cells, and several biomarkers, such as miRNAs, cadena α dek receptor pra la interleukin % (IL5Rα) and soluble IL5Rα in patients with severe eosinophilic asthma. For this, basophil and innate cells type 2 (ILC2) populations will be monitored in different point-time of treatment: 8 week (V1), 6 months (V2) and 1 year (V3) in blood and sputum samples. Also, follow-up IL5Rα expression on a cell surface of eosinophils, basophils and ILC2 from peripheral blood and sputum of patients treated with or or without benralizumab. Determination of IL5Rα levels will be performed by flow cytometry

For this: 1. Investigators will monitor basophil miRNAs changes with benralizumab analyzing miRNAS profile of isolated basophil before and after benralizumab treatment. 2. Also, in vitro characterization of benralizumab effects on functionality of human basophils (isolated from allergic asthmatic patients) and human cell line KU812, measuring apoptosis, activation, degranulation and histamine release will be performed.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Asthma; Eosinophilic

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * .It is mandatory that all patients can comprehend the study requirements and provide informed consent for their participation in MEGA. Group A: * Adult people (≥ 18 and ≤ 80 years old) with eosinophilic severe asthma requiring high-dose inhaled corticosteroids plus long-acting beta agonists (with or without long-acting muscarinic antagonist or Montelukast or oral corticosteroids) * Benralizumab treatment approved. Group B: .Patients with allergic asthma (prick test or RAST positive). Exclusion Criteria: * Patients with continuous OCS treatment * Patients with Immunosuppressive drugs * Patients with primary or secondary immune deficiency, * Patients with chronic or/and concomitant disease, presence of severe systemic disease or cancer, * Patients with possible infestation by parasites. * Patients with other acute or chronic active lung disorders Patients with significant psychiatric disorders * Patients with biological treatment will be excludes for group B

Outcomes

Primary Outcomes

Fold changes in number of basophils

Fold changes in number of basophils after 8 week, 6 months and 1 year of benralizumab treatment (Fasenra®, Astra Zeneca) in blood and sputum in patients with severe eosinophilic asthma

Time frame: From 1 to 12 months

Fold changes in number of innate inmmune cells

Fold changes in number of innate immune cells s after 8 week, 6 months and 1 year of benralizumab treatment (Fasenra®, Astra Zeneca) in blood and sputum in patients with severe eosinophilic asthma

Time frame: From 1 to 12 months

The fold changes of IL-5R expression in basophils

The fold changes of IL-5R expression in basophils after 8 week, 6 months and 1 year of benralizumab treatmen

Time frame: From 1 to 12 months

The fold changes of f IL-5R expression in innate lymphoid cells

The fold changes of f IL-5R expression in innate lymphoid cells after 8 week, 6 months and 1 year of benralizumab treatment

Time frame: From 1 to 12 months

Secondary Outcomes

Fold changes of miRNAs profile in basophils

1\. Fold changes of miRNAs profile in basophils after tratment of Benralizumab in in patients with severe eosinophilic asthma treatment.

Time frame: From 6 to 18

Fold changes of serum IL-5R

Fold changes of serum IL-5R (microg/ml) in patients treated with benralizumab

Time frame: Fromm 6 to 12

Effect of benralizumab in basophil apoptosis

The effect of benralizumab in basophil apoptosis isolated from from allergic asthmatic patients will be measure by fold change of annexin V