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Aberrant expression of cell-free nucleosomes in dermatomyositis/polymyositis
Danli Zhong1, Chanyuan Wu1, Jingjing Bai1
1Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
Abstract:
Nucleosomes are typically located intracellularly, and extracellular levels of nucleosomes indicated the degree of cell death. We postulated aberrant nucleosomes expression in dermatomyositis (DM) and polymyositis (PM). To assess the aberrant expression of circulating nucleosomes in DM and polymyositis. 76 consecutive DM and PM patients from 1 September 2017 to 31 October 2018 were enrolled in this study, in addition to 20 healthy controls. The levels of circulating nucleosomes, with 16 kinds of detectable myositis-specific antibodies (MSAs) were detected in IIMs patients using enzyme-linked immunosorbent assay kit (ELISA). Receiver operating characteristic (ROC) curve analysis was performed for evaluating the ability of this candidate marker for detecting DM/PM. The results showed that the levels of circulating nucleosomes in DM/PM patients were significantly higher than that in normal individuals. Specifically, elevated levels of nucleosomes were associated with MDA5 Ab, ARS, and TIF1γAb. In addition, elevated levels of circulating nucleosomes correlated with skin eruption. This study has evidenced nucleosomes as a potential new biomarker of DM/PM. Aberrant nucleosomes expression occurs in myositis patients and the difference in nucleosomes expression between patients with and without skin eruption is statistically significant. A unique expression profile of elevated serum nucleosomes was detected in DM/PM-MDA5 Ab(+), ASS, and TIF1γAb(+).
Insights
Extracellular nucleosome levels are significantly higher in patients with dermatomyositis (DM) and polymyositis (PM), indicating nucleosomes as a potential biomarker for these inflammatory myopathies.
Area of Science:
- Immunology
- Cell Biology
- Rheumatology
Background:
- Nucleosomes are primarily intracellular; elevated extracellular levels typically signify cell death.
- Aberrant nucleosome expression is hypothesized in inflammatory myopathies like dermatomyositis (DM) and polymyositis (PM).
Purpose of the Study:
- To investigate and assess the aberrant expression of circulating nucleosomes in DM and PM patients.
- To evaluate nucleosomes as a potential diagnostic biomarker for DM and PM.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to detect circulating nucleosome levels in 76 DM/PM patients and 20 healthy controls.
- Myositis-specific antibodies (MSAs) and clinical data, including skin eruption, were analyzed.
- Receiver operating characteristic (ROC) curve analysis assessed the diagnostic potential of nucleosomes.
Main Results:
- DM/PM patients exhibited significantly higher circulating nucleosome levels compared to healthy individuals.
- Elevated nucleosome levels correlated with specific myositis-specific antibodies: MDA5 Ab, ARS, and TIF1γAb.
- Increased nucleosome levels were also associated with the presence of skin eruption in patients.
Conclusions:
- Circulating nucleosomes represent a potential novel biomarker for diagnosing DM and PM.
- Aberrant nucleosome expression is confirmed in myositis patients, with significant differences observed in those with skin eruption.
- A distinct profile of elevated serum nucleosomes was identified in DM/PM patients positive for MDA5 Ab, ASS, and TIF1γAb.
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