Hansen Sune Holm, Ostrowski Sisse Rye, Andersen Niels Smedegaard, Friis Lone Smidstrup, Kornblit Brian, Petersen Søren Lykke, Schjødt Ida, Sengeløv Henrik, Gjærde Lars Klingen
Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Transplant Cell Ther. 2025 May;31(5):301.e1-301.e10. doi: 10.1016/j.jtct.2025.02.015. Epub 2025 Feb 18.
Circulating nucleosomes are representative of cell death, which is a feature of acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We explored whether plasma nucleosome levels were prognostic for acute GVHD. We examined the level of circulating nucleosomes in 131 patients who underwent a myeloablative allo-HSCT between June 2015 and August 2018. The measurements were made using quantitative photometric sandwich-ELISA on stored plasma samples obtained pretransplantation (at a median of day -23) and around days +7, +14, and +28 after allo-HSCT. The median plasma nucleosome level remained constant until day +28, where they increased significantly (P < .001 compared to all other times of measurement). The plasma nucleosome level at day +28 was inversely associated with the risk of later grade II to IV acute GVHD (odds ratio [OR] 0.86 per 5 arbitrary unit [AU] increase [95% confidence intervals (CI): 0.66 to 0.99], P = .03), also after adjustment for risk factors of acute GVHD (OR 0.78 per 5 AU increase [95% CI: 0.56 to 0.96], P = .01). We found no support for an association between the plasma level of nucleosomes measured pretransplantation or around day +7 or +14 and the risk of subsequent grade II to IV acute GVHD. We observed a positive correlation between nucleosomes, suppressor of tumorigenesis 2, and C-reactive protein at day +28 (Spearman's ρ = 0.522, P < .001; and Spearman's ρ = 0.386, P < .001; respectively). A lower level of plasma nucleosomes at day +28 after HSCT was associated with a higher risk of subsequent acute GVHD. Additional studies are needed to validate circulating nucleosomes as a prognostic biomarker of acute GVHD.
循环核小体是细胞死亡的代表，而细胞死亡是异基因造血干细胞移植（allo-HSCT）后急性移植物抗宿主病（GVHD）的一个特征。我们探讨了血浆核小体水平是否可作为急性GVHD的预后指标。我们检测了2015年6月至2018年8月期间接受清髓性allo-HSCT的131例患者的循环核小体水平。检测采用定量光度夹心酶联免疫吸附测定法，对移植前（中位时间为-23天）以及allo-HSCT后第7、14和28天左右采集的储存血浆样本进行检测。血浆核小体水平中位数在第28天之前保持稳定，之后显著升高（与所有其他检测时间相比，P <.001）。第28天的血浆核小体水平与随后发生II至IV级急性GVHD的风险呈负相关（每增加5个任意单位[AU]，优势比[OR]为0.86 [95%置信区间(CI)：0.66至0.99]，P =.03），在对急性GVHD的危险因素进行校正后也是如此（每增加5 AU，OR为0.78 [95% CI：0.56至0.96]，P =.01）。我们没有发现移植前或第7天或第14天左右检测的血浆核小体水平与随后发生II至IV级急性GVHD的风险之间存在关联。我们观察到在第28天时，核小体、肿瘤发生抑制因子2和C反应蛋白之间存在正相关（斯皮尔曼相关系数ρ分别为0.522，P <.001；以及斯皮尔曼相关系数ρ为0.386，P <.001）。HSCT后第28天血浆核小体水平较低与随后发生急性GVHD的风险较高相关。需要进一步的研究来验证循环核小体作为急性GVHD预后生物标志物的作用。
