Lateef Sundus S, Ward Grace A, Li Haiou, Pantoja Carla, Florida Elizabeth, Hong Christin G, Rodante Justin, Keel Andrew, Chen Marcus Y, Sorokin Alexander V, Playford Martin P, Mehta Nehal N
Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
JID Innov. 2023 Nov 3;4(1):100243. doi: 10.1016/j.xjidi.2023.100243. eCollection 2024 Jan.
Psoriasis (PSO) is a chronic and systemic inflammatory autoimmune disease associated with atherosclerosis and myocardial infarction. Given that atherosclerosis is both inflammation and immune driven, we sought to expand on known immune and inflammatory biomarkers in a PSO cohort. In this study, we focus on oxidized mtDNA (ox-mtDNA), a product of cells undergoing pyroptosis, including keratinocytes, which was quantified in patients with PSO and individuals without PSO by ELISA. Patients with PSO had significantly higher ox-mtDNA levels than healthy subjects (mean ± SD = 9246 ± 2518 pg/ml for patients with PSO vs 7382 ± 2506 pg/ml for those without; = .006). Importantly, ox-mtDNA was positively associated with IL-17a (β = 0.25; = .03) and low-density granulocytes (β = 0.37; = .005) but negatively associated with high-density lipoprotein-cholesterol (β = -0.29; = .006). After adjusting for traditional cardiovascular risk factors, we found that ox-mtDNA was associated with noncalcified coronary burden, which was measured by coronary computed tomography angiography (β = 0.19; = .003). Biologic-naïve patients with PSO receiving anti-IL-17a therapy had a 14% decrease in ox-mtDNA (mean ± SD: 10540 ± 614 pg/ml at baseline to 9016 ± 477 pg/ml at 1 year; = .016) and a 10% reduction in noncalcified coronary artery burden (mean ± SD: 1.06 ± 0.45 at baseline, reducing to 0.95 ± 0.35 at 1 year; = .0037). In summary, levels of ox-mtDNA in PSO are associated with measures of coronary plaque formation, indicating that this biomarker may be an autoimmune-driven early atherosclerotic feature.
银屑病（PSO）是一种慢性全身性炎症性自身免疫性疾病，与动脉粥样硬化和心肌梗死相关。鉴于动脉粥样硬化是由炎症和免疫驱动的，我们试图在银屑病队列中扩展已知的免疫和炎症生物标志物。在本研究中，我们重点关注氧化型线粒体DNA（ox-mtDNA），这是包括角质形成细胞在内的发生焦亡的细胞的产物，通过酶联免疫吸附测定法（ELISA）对银屑病患者和非银屑病个体进行定量。银屑病患者的ox-mtDNA水平显著高于健康受试者（银屑病患者的平均值±标准差=9246±2518 pg/ml，而无银屑病者为7382±2506 pg/ml；P=.006）。重要的是，ox-mtDNA与白细胞介素-17a呈正相关（β=0.25；P=.03），与低密度粒细胞呈正相关（β=0.37；P=.005），但与高密度脂蛋白胆固醇呈负相关（β=-0.29；P=.006）。在调整传统心血管危险因素后，我们发现ox-mtDNA与通过冠状动脉计算机断层扫描血管造影术测量的非钙化冠状动脉负荷相关（β=0.19；P=.003）。接受抗白细胞介素-17a治疗的未使用过生物制剂的银屑病患者的ox-mtDNA降低了14%（平均值±标准差：基线时为10540±614 pg/ml，1年后为9016±477 pg/ml；P=.016），非钙化冠状动脉负荷降低了10%（平均值±标准差：基线时为1.06±0.45，1年后降至0.95±0.35；P=.0037）。总之，银屑病患者的ox-mtDNA水平与冠状动脉斑块形成的指标相关，表明该生物标志物可能是自身免疫驱动的早期动脉粥样硬化特征。
