Galectin-10 in serum extracellular vesicles reflects asthma pathophysiology
Authors: Hanako Yoshimura, Yoshito Takeda, Yuya Shirai, Makoto Yamamoto, Daisuke Nakatsubo, Saori Amiya, Takatoshi Enomoto, Reina Hara, Yuichi Adachi, Ryuya Edahiro, Moto Yaga, Kentaro Masuhiro, Taro Koba, Miho Itoh-Takahashi, Mana Nakayama, So Takata, Yuki Hosono, Sho Obata, Masayuki Nishide, Akinori Hata, Masahiro Yanagawa, Satoko Namba, Michio Iwata, Momoko Hamano, Haruhiko Hirata, Shohei Koyama, Kota Iwahori, Izumi Nagatomo, Yasuhiko Suga, Kotaro Miyake, Takayuki Shiroyama, Kiyoharu Fukushima, Shinji Futami, Yujiro Naito, Takahiro Kawasaki, Kenji Mizuguchi, Yusuke Kawashima, Yoshihiro Yamanishi, Jun Adachi, Mari Nogami-Itoh, Shigeharu Ueki, Atsushi Kumanogoh
Journal: Journal of Allergy and Clinical Immunology (2024)

BackgroundNovel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes.ObjectiveWe sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs).MethodsWe performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps.ResultsWe identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo.ConclusionNovel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches. Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes. We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs). We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps. We identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo. Novel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches.