We found that miR-124 ameliorated AIA by suppressing critical prerequisites for arthritis development, such as RANKL and NFATc1. Thus, miR-124a is a candidate for therapeutic use for human rheumatoid arthritis.
Previous studies from various countries have reported anti-dense fine speckled pattern (DFS)70 antibody prevalence but few studies have been from Asia. We investigated the prevalence of anti-DFS70 autoantibodies in a Japanese cohort of healthy individuals (HI) and patients with antinuclear antibody-associated autoimmune rheumatic diseases (AARD).
Enzyme-linked immunosorbent assay and indirect immunofluorescence were performed using samples from 250 HI and 276 AARD patients.
The overall anti-DFS70 antibody prevalence in HI was 16.4%, with 12.8% for males and 20.0% for females (sex difference;
P
= .12). In AARD patients, the anti-DFS70 antibody prevalence in systemic lupus erythematosus, mixed connective tissue disease, systemic sclerosis, dermatomyositis and polymyositis (DM/PM), Sjögren syndrome, and rheumatoid arthritis (RA) was 22.1%, 14.3%, 14.3%, 3.0%, 21.3%, and 18.1%, respectively (no significant difference between AARD patients except DM/PM and HI). The prevalence of isolated anti-DFS70 antibody in HI and all AARD patients excluding RA was 14.8% (37/250) and 4.4% (9/204), respectively (
P
<
.01 vs HI). Among anti-DFS70 antibody-positive cases, 63.4% (26/41) were DFS pattern by IIF and 23.5% (8/34) were HI and AARD patients excluding RA, respectively.
The anti-DFS70 antibody prevalence in HI and AARD patients in Japan was similar. Furthermore, the anti-DFS70 antibody prevalence in HI and AARD in Japan is higher than in HI and AARD in regions other than Asia. This makes AARD differential diagnosis by antinuclear antibody screening difficult.
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.
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