SARS-CoV-2 ORF8驱动了先前存在的免疫媒介炎症性疾病中的骨质细胞生成
Ivonne Melano1, Tamiris Azamor1,2, Camila Cs Caetano1
1Infection Biology Program, Global Center for Pathogen Research and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
JCI insight
|December 20, 2024
概括
患有免疫媒介性炎症性疾病 (IMID) 的患者面临严重的COVID-19和骨质损失. 这就是SARS-CoV-2病毒.
科学领域:
- 免疫学 免疫学 免疫学
- 骨生物学 骨生物学 骨生物学
- 病毒学 病毒学
背景情况:
- 患有免疫媒介性炎症性疾病 (IMIDs) 的患者,如类风湿性关节炎 (RA),患重症COVID-19的风险增加.
- SARS-CoV-2 感染与骨周转率降低和骨损失增加有关,但潜在的机制尚不清楚.
- 了解SARS-CoV-2如何影响IMID患者的骨健康对于管理共存疾病至关重要.
研究的目的:
- 为了确定特定的免疫媒介,在暴露于SARS-CoV-2后加剧了先前存在的IMID.
- 调查SARS-CoV-2ORF8在IMID患者骨病理学中的作用.
主要方法:
- 分析了来自四个组的血样本:健康,仅IMID,仅COVID-19,以及COVID-19+IMID.
- 利用高通量多重化蛋白质组学来分析1500种蛋白质生物标志物.
- 在体外用SARS-CoV-2 ORF8治疗了类风湿性关节炎衍生的人类骨质母细胞 (RA-hOBs).
主要成果:
- 在患有IMID的COVID-19患者中鉴定出148种独特的生物标志物,包括炎症性细胞因子 (例如IL-17F) 和骨质再吸收标志物的升高.
- 在COVID-19 + IMID组中检测到长期循环的SARS-CoV-2 ORF8.
- 对于RA-hOBs的ORF8治疗增加了炎症标志物和RANKL/骨质保护素比率,促进了骨质结晶形成.
结论:
- 暴露于SARS-CoV-2会通过ORF8驱动的炎症和骨质结晶生成加剧IMID.
- 在IMID患者中确定了管理COVID-19诱导的骨病理的潜在治疗点.
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