Identification of plexin D1 on circulating extracellular vesicles as a potential biomarker of polymyositis and dermatomyositis.

Kenichi Uto, Koji Ueda, Takaichi Okano, Kengo Akashi, Soshi Takahashi, Yuji Nakamachi, Takamitsu Imanishi, Hiroyuki Awano, Akio Morinobu, Seiji Kawano, Jun Saegusa

Rheumatology (Oxford, England) 2022 Apr 11

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We aimed to identify disease-specific surface proteins on extracellular vesicles (EVs) as novel serum biomarkers of PM/DM. We performed liquid chromatography-tandem mass spectrometry (LC/MS) on purified EVs from sera of 10 PM/DM patients, 23 patients with other autoimmune diseases and 10 healthy controls (HCs). We identified membrane proteins preferentially present in EVs of PM/DM patients by bioinformatics and biostatistical analyses. We developed an EV sandwich ELISA for directly detecting serum EVs expressing disease-specific membrane proteins and evaluated their clinical utility using sera from 54 PM/DM, 24 RA, 20 SLE, 13 SSc and 25 Duchenne and Becker types of muscular dystrophy (DMD/BMD) patients and 36 HCs. LC/MS analysis identified 1220 proteins in serum EVs. Of these, plexin D1 was enriched in those from PM/DM patients relative to HCs or patients without PM/DM. Using a specific EV sandwich ELISA, we found that levels of plexin D1+ EVs in serum were significantly greater in PM/DM patients than in HCs or RA, SLE or DMD/BMD patients. Serum levels of plexin D1+ EVs were greater in those PM/DM patients with muscle pain or weakness. Serum levels of plexin D1+ EVs were significantly correlated with levels of aldolase (rs = 0.481), white blood cells (rs = 0.381), neutrophils (rs = 0.450) and platelets (rs = 0.408) in PM/DM patients. Finally, serum levels of plexin D1+ EVs decreased significantly in patients with PM/DM in clinical remission after treatment. We identified levels of circulating plexin D1+ EVs as a novel serum biomarker for PM/DM. © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Citation

Kenichi Uto, Koji Ueda, Takaichi Okano, Kengo Akashi, Soshi Takahashi, Yuji Nakamachi, Takamitsu Imanishi, Hiroyuki Awano, Akio Morinobu, Seiji Kawano, Jun Saegusa. Identification of plexin D1 on circulating extracellular vesicles as a potential biomarker of polymyositis and dermatomyositis. Rheumatology (Oxford, England). 2022 Apr 11;61(4):1669-1679