Serum proteomic analyses to identify systemic inflammation driving asthma exacerbations

Résumé fourni par la source

Asthma exacerbations represent an unmet clinical need, and the underlying mechanisms are not fully understood. We aimed to identify systematic inflammatory changes that occur during an exacerbation to provide further insight. 44 paired serum samples (baseline/at exacerbation) from the Asthma Phenotyping Exacerbations (APEX) study were analysed. The NULISA™ proteomic analysis platform was used to measure serum levels of 250 inflammatory proteins to identify differential expression (P<0.05). To complement this approach, we measured the same panel of proteins in the Investigating Poor Response to Monoclonal Therapy in Asthma (PROCLAIM) study with 40 paired serum samples (Pre/12 weeks post-mepolizumab - a non-exacerbation cohort). We hypothesised we would see suppression of the inflammatory mediators identified in APEX. 22 proteins were differentially expressed in APEX samples including upregulation of several Type 2 inflammatory cytokines at exacerbation; IL-33 (1.11-fold), IL-13 (1.18-fold) and IL-5 (1.29-fold) but also Type 17 inflammatory protein IL-17A (1.15-fold). Type 1 inflammatory protein, IL-12p70 (-1.14-fold) was downregulated at exacerbation. Of these 22 proteins, IL-5RA expression was reduced post-mepolizumab in PROCLAIM. Inversely, CCL24, IL-22 and TNFSF9 were increased after mepolizumab dosing. IL-5 was elevated in serum post-mepolizumab as described by others. This study is the first-in-kind to examine systemic inflammation during an asthma exacerbation using the NULISA™ assay, with a heterogenous profile observed. Ongoing studies aim to further investigate subgroups of patients with T2/non-T2 airway inflammation at exacerbation.

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