​Asthma is a multifactorial and heterogeneous disease resulting from interactions between multiple genetic and environmental factors. It is defined by chronic inflammation of the airways and by bronchial hyperreactivity responsible for the characteristic symptoms of the disease (wheezing, coughing and dyspnea). In most children, asthma is controlled with mild to moderate doses of inhaled corticosteroids. However, nearly 5% of children with severe asthma (SA) remain symptomatic despite high doses of corticosteroids.
Allergy is the most common cause of asthma and, in children, the disease has long been considered a type 2 disorder, i.e. mediated by cytokines* secreted by type 2 T-helper lymphocytes, the Th2. However, recent studies have shown that bronchoalveolar lavage (BAL) from children with SA may instead have a mixed immune signature, with a dominant Th1 response. To date, very few studies have attempted to characterize without a priori the immune signature of SA children compared to non-asthmatic children. Most studies have focused on a single immune cell or cytokine type, with sometimes conflicting results.

As the inflammatory profiles of SA children are particularly complex, the authors propose here to identify immune signatures associated with the clinical phenotypes of SA syndrome, by conducting a global study on a cohort of 20 children with SA and 10 control subjects of the same age with chronic respiratory disorders other than asthma. They seek to identify sets of immune constituents that would distinguish SA children from control subjects by comprehensive analysis of cells and soluble components measured in BAL and blood. A first analysis showed the lack of correlation between local and circulating immune factors, and the association of some immunological parameters with demographic and clinical data. All data were then modeled using multivariate (partial least squares discriminant analysis, PLS-DA) and univariate (Mann-Whitney tests) supervised analyses, which were then combined and allowed the identification of the most discriminating and significant constituents between groups. A model capable of distinguishing children with SA from controls with a specificity of 80% and a sensitivity of 100% was obtained. Moreover, among severe asthmatics, a specific signature distinguishes "frequent exacerbators" (having had more than 2 exacerbations in the previous year) from non-frequent exacerbators. Circulating "biomarkers" are proposed to help in the diagnosis and follow-up of these patients in a non-invasive way.

Despite some limitations (small number of subjects included and lack of healthy controls), untargeted multivariate analysis of a large set of immune constituents may allow the identification of a biological immune signature of SA, which will help to better define its pathogenesis and endotypes, and thus identify new targets for its diagnosis, prediction and personalized treatment.

*Cytokines are soluble proteins that act as messengers by ensuring communication between the cells of the immune system, including T lymphocytes.

Contact : Karine Adel-Patient karine.patient@cea.fr