NHERF2 as a Novel Biomarker for Distinguishing MAC Pulmonary Disease from Tuberculosis Based on Proteome Analysis of Serum Extracellular Vesicles
Nontuberculous mycobacterial pulmonary disease (NTM-PD), mainly caused by <i>Mycobacterium avium</i> complex (MAC), and pulmonary tuberculosis (TB) are emerging health problems worldwide. However, because their clinical features are often similar, it remains difficult to differentiate NTM-PD from TB when the diagnosis cannot be made by sputum culture. To investigate potential serum biomarkers, we conducted non-targeted proteome analysis on serum extracellular vesicles (EVs) collected from 10 patients with MAC pulmonary disease (MAC-PD), 7 patients with TB, and 10 healthy controls. A total of 2614 proteins were identified in the discovery cohort. The EV protein signature from patients with NTM-PD and TB reflected infectious diseases and inflammatory response pathways. Among the identified proteins, the expression of Na<sup>+</sup>/H<sup>+</sup> exchanger regulatory factor 2 (NHERF2) was significantly elevated in patients with MAC-PD compared with healthy controls and patients with TB. Moreover, upregulation of NHERF2 was confirmed by immunoblotting of serum EVs and immunohistochemistry of lungs with mycobacterial infection. Our findings highlight that NHERF2 in serum EVs might be a potential biomarker for distinguishing MAC-PD from TB, possibly reflecting the pathogenesis of MAC-PD.
Authors
- Kazutake Tsujikawa (ORCID: https://orcid.org/0000-0003-1870-9790)
- M Itoh (ORCID: https://orcid.org/0000-0001-7917-2830)
- Atsushi Kumanogoh (ORCID: https://orcid.org/0000-0003-4749-7117)
- Yujiro Naito
- Shohei Koyama (ORCID: https://orcid.org/0000-0002-6897-9417)
- Koji Ueda (ORCID: https://orcid.org/0000-0001-9066-4959)
- Yukihiro Yano (ORCID: https://orcid.org/0000-0002-6829-1778)
- Kentaro Masuhiro (ORCID: https://orcid.org/0000-0002-8785-1726)
- Kota Iwahori (ORCID: https://orcid.org/0000-0002-9891-6003)
- Izumi Nagatomo (ORCID: https://orcid.org/0000-0001-5382-4327)
- Satoshi Nojima (ORCID: https://orcid.org/0000-0002-5124-0026)
- Hiroaki Hase
- Ryuya Edahiro (ORCID: https://orcid.org/0000-0001-5009-6408)
- Hanako Yoshimura (ORCID: https://orcid.org/0000-0002-3717-3963)
- Takatoshi Enomoto (ORCID: https://orcid.org/0000-0002-1771-6684)
- Yoshito Takeda (ORCID: https://orcid.org/0000-0003-2905-6537)
- Reina Hara (ORCID: https://orcid.org/0000-0001-7013-4328)
- Mana Nakayama
- Maiko Naito (ORCID: https://orcid.org/0000-0002-4360-7043)
- Kotaro Miyake (ORCID: https://orcid.org/0000-0002-6441-1699)
- Yuya Shirai (ORCID: https://orcid.org/0000-0002-0518-9020)
- Haruhiko Hirata (ORCID: https://orcid.org/0000-0002-1134-7283)
- T. Matsuki (ORCID: https://orcid.org/0000-0002-4416-6083)
- Takayuki Shiroyama (ORCID: https://orcid.org/0000-0002-2816-9428)
- Masahide Mori (ORCID: https://orcid.org/0009-0007-9223-3854)
- Makoto Yamamoto
Institutions
- Japan Agency for Medical Research and Development (JP)
- Toneyama National Hospital (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
- Japanese Foundation For Cancer Research (JP)
- Osaka International University (JP)
- The University of Osaka (JP)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-01-29
- DOI
- https://doi.org/10.3390/ijms26031155
- Citations
- 4
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 3.22
Funders
- Uehara Memorial Foundation
- Japanese Respiratory Foundation
- Japan Society for the Promotion of Science