Rheumatology (Oxford, England) · 2022
Identification of plexin D1 on circulating extracellular vesicles as a potential biomarker of polymyositis and dermatomyositis.
СтатьяНазвание и аннотация: Перевод в очереди
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Uto Kenichi, Ueda Koji, Okano Takaichi, Akashi Kengo, Takahashi Soshi, Nakamachi Yuji, Imanishi Takamitsu, Awano Hiroyuki, Morinobu Akio, Kawano Seiji, Saegusa Jun
Аннотация
OBJECTIVES: We aimed to identify disease-specific surface proteins on extracellular vesicles (EVs) as novel serum biomarkers of PM/DM.
METHODS: 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.
RESULTS: 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.
CONCLUSION: We identified levels of circulating plexin D1+ EVs as a novel serum biomarker for PM/DM.
METHODS: 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.
RESULTS: 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.
CONCLUSION: We identified levels of circulating plexin D1+ EVs as a novel serum biomarker for PM/DM.