Roodenburg Sharyn A, Hartman Jorine E, Eichhorn Ilse A, Slebos Dirk-Jan, Pouwels Simon D
University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, The Netherlands.
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands.
ERJ Open Res. 2024 Jul 15;10(4). doi: 10.1183/23120541.00240-2024. eCollection 2024 Jul.
Damage-associated molecular patterns (DAMPs) are endogenous danger signals that alert and activate the immune system upon cellular damage or death. It has previously been shown that DAMP release is increased in patients with COPD, leading to higher levels in extracellular fluids such as serum. In the current study we investigated whether the serum levels of DAMPs were associated with survival rates in COPD patients.
A panel of seven DAMPs, consisting of HMGB1, fibrinogen, α-defensin, heat shock protein 70, S100A8, galectin-9 and double-stranded DNA (dsDNA), was measured in serum of 949 severe COPD patients. Maximally selected rank statistics was used to define cut-off values and a Cox proportional hazards model was used to evaluate the effect of high or low DAMP levels on 4-year survival. For DAMPs that were found to affect survival significantly, baseline characteristics were compared between the two DAMP groups.
Out of the seven DAMPs, only dsDNA was significantly associated with 4-year survival. Patients with elevated serum level of dsDNA had higher 4-year mortality rates, lower FEV % predicted values and higher emphysema scores.
In conclusion, in a clinical cohort of 949 patients with moderate-to-severe COPD, elevated serum levels of dsDNA were associated with a higher risk of death. This study further illustrates the potential role of circulating DAMPs, such as dsDNA, in the progression of COPD. Together, the results of this study suggest that levels of circulating dsDNA might serve as an additional prognostic biomarker for survival in COPD patients.
损伤相关分子模式（DAMPs）是内源性危险信号，在细胞损伤或死亡时会警示并激活免疫系统。此前已有研究表明，慢性阻塞性肺疾病（COPD）患者体内DAMPs的释放增加，导致血清等细胞外液中的水平升高。在本研究中，我们调查了COPD患者血清中DAMPs水平与生存率是否相关。
在949例重度COPD患者的血清中检测了一组由高迁移率族蛋白B1（HMGB1）、纤维蛋白原、α-防御素、热休克蛋白70、S100A8、半乳糖凝集素-9和双链DNA（dsDNA）组成的七种DAMPs。使用最大选择秩统计来定义临界值，并使用Cox比例风险模型评估高或低DAMP水平对4年生存率的影响。对于发现对生存有显著影响的DAMPs，比较了两个DAMP组之间的基线特征。
在七种DAMPs中，只有dsDNA与4年生存率显著相关。血清dsDNA水平升高的患者4年死亡率更高，预测的第1秒用力呼气容积（FEV）百分比更低，肺气肿评分更高。
总之，在一个由949例中重度COPD患者组成的临床队列中，血清dsDNA水平升高与更高的死亡风险相关。本研究进一步说明了循环DAMPs，如dsDNA，在COPD进展中的潜在作用。本研究结果共同表明，循环dsDNA水平可能作为COPD患者生存的额外预后生物标志物。
