Asthma is a common chronic bronchial disease affecting 300 million people worldwide. The disease can be severe when it is not managed properly or when it is not controlled by treatments. Asthma is characterized by bronchial inflammation, bronchial hyperreactivity and tissue remodeling. Symptoms include episodes of coughing, dyspnoea and wheezing in relation with bronchial obstruction. The evolution is marked by the occurrence of exacerbations (increase of symptoms), most often triggered by viral infections, mostly due to rhinoviruses. The treatment of asthma is based on inhaled corticosteroid therapy sometimes combined with other treatments that help control the majority of asthma. However, about 10% of patients suffer from persistent symptoms despite these treatments.
Natural killer (NK) cells are important actors of the antiviral innate immune response and are present in high numbers in the lungs. However, their role in severe asthma and its virus-induced exacerbations is unknown.
The purpose of this work is to characterize NK cells in severe asthma in order to identify molecules expressed differently from control subjects. The goal is to assess whether these molecules could be potential biomarkers of a severe asthma subtype, also known as the endotype, and/or be the molecular control for exacerbation. The advantage of identifying biomarkers for inflammatory diseases lies in their usefulness in establishing a correct diagnosis, monitoring the progress of the disease and the effectiveness of treatments. The secondary objectives are to characterize the activation of NK cells in response to in vitro rhinovirus infection of different types, in monoculture or in a model of interaction with a bronchial epithelium, and identify one or more molecules involved in the interaction between bronchial epithelial cells and NK cells.
Consent form read, understood, approved and signed before any study procedure
Membership of a social security scheme or beneficiary of such a scheme
Patient aged over 18
Person subject to a legal protection measure
Vulnerable population: minors, persons under guardianship or trusteeship or persons deprived of their rights to liberty by court order.
women with a known pregnancy
Inability or refusal to comply with research requirements
Parallel
blood sample
Biological/VaccineBlood sample (56mL) taken in a heparin tube
Changes in expression of one or more molecules on the surface of NK cells
Rationale for choice of primary endpoint: Our aim is to phenotype NK cells in different groups of severe asthma patients compared with control subjects, in order to identify at least one marker of disease discrimination on these cells. We are therefore looking for previously unknown changes in the expression of one or more molecules.
Measurement of NK cell activation
Change From Baseline in the expression of CD107, CD69 and interferon-ɣ.
Measurement of NK cell-induced epithelial cell activation and viability
Change From Baseline in epithelial cell cohesion, mucin and cytokine (IL-8, type I interferon, IL-33 and TSLP) production
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