I n a study published in The Journal of Allergy and Clinical Immunology, researchers sought to identify novel biomarkers from serum extracellular vesicles that reflect tissue pathology in bronchial asthma (BA).
“Clinically, compared to sputum samples, blood samples are much easier to collect and can be collected repeatedly. Therefore, identification of biomarkers of BA that reflect tissue pathology and can be easily detected in serum is urgently needed,” wrote Hanako Yoshimura, MD, and colleagues. “In chronic airway diseases, in cluding BA, rapidly accumulating evidence has demonstrated that extracellular vesicles have a potential role as biomarkers and drug delivery systems in precision medicine and pathology.”
They conducted data-independent acquisition (DIA) of serum extracellular vesicles from four healthy controls, four patients with noneosinophilic asthma (NEA), and four patients with eosinophilic asthma (EA) to identify novel biomarkers for BA. The researchers then validated EA-specific biomarkers in a larger cohort of 61 patients with BA and 23 controls. They performed further validation on 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps.
The researchers identified a total of 3,032 pro – teins, with 23 showing differential expression in EA. Using ingenuity pathway analysis, the investigators determined that the protein signatures for each phenotype reflected disease characteristics. They identified 5 EA-specific biomarkers: galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. Gal10 in extracellular vesicles demonstrated superior diagnostic capability and airway obstruction detection compared with eosinophils. In patients with rhinosinusitis, researchers identified 1,752 and 8,413 proteins from extracellular vesicles and tissues, respectively. Among the 11 biomarkers identified from EVs and tissues in patients with chronic rhinosinusitis with nasal polyps, five (including Gal10 and eosinophil peroxidase) showed significant correlations between extracellular vesicles and tissues. Gal10 release from extracellular vesicles was associated with eosinophil extracellular trapped cell death both in vitro and in vivo.
The researchers concluded that novel biomarkers such as Gal10 from serum extracellular vesicles reflected disease pathophysiology in BA and may represent a new target for liquid biopsy approaches.
“Monitoring the levels of eosinophil granules and associated proteins could be advantageous over monitoring eosinophil counts alone for personalized medicine in heterogeneous BA. Additionally, it may be useful as a tool to identify patients with BA or COPD with type 2 inflammation among those with low blood eosinophil counts,” Dr. Yoshimura and coauthors explained.