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

OBJECTIVES We aimed to identify disease-specific surface proteins on extracellular vesicles (EVs) as novel serum biomarkers of polymyositis and dermatomyositis (PM/DM). METHODS We performed liquid chromatography-tandem mass spectrometry (LC/MS) on… Click to show full abstract

OBJECTIVES We aimed to identify disease-specific surface proteins on extracellular vesicles (EVs) as novel serum biomarkers of polymyositis and dermatomyositis (PM/DM). METHODS We performed liquid chromatography-tandem mass spectrometry (LC/MS) on purified EVs from sera of 10 PM/DM, 23 patients with other autoimmune diseases and 10 healthy controls (HC). We identified membrane proteins preferentially present in EVs of PM/DM patients by bioinformatics and biostatistical analyses. We developed EV sandwich ELISA for directly detecting serum EVs expressing disease-specific membrane proteins and evaluated their clinical utility using sera of 54 PM/DM, 24 rheumatoid arthritis (RA), 20 systemic lupus erythematosus (SLE), 13 systemic sclerosis, 25 Duchenne and Becker muscular dystrophy (DMD/BMD) patients, and 36 HC. RESULTS LC/MS analysis identified 1,220 proteins in serum EVs. Of these, Plexin D1 was enriched in those from PM/DM patients relative to HC or patients without PM/DM. Using a specific EV sandwich ELISA, we found that levels of Plexin D1-positive EVs (Plexin D1+ EVs) in serum were significantly greater in PM/DM patients than in HC, RA or 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. CONCLUSION We have identified levels of circulating Plexin D1+ EVs as a novel serum biomarker for PM/DM.

Keywords: extracellular vesicles; polymyositis dermatomyositis; plexin; plexin evs; serum

Journal Title: Rheumatology
Year Published: 2021

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