Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Haematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Sci Rep. 2021 Dec 14;11(1):23971. doi: 10.1038/s41598-021-01952-6.
Cytokine-specific autoantibodies (c-aAbs) represent an emerging field in endogenous immunodeficiencies, and the immunomodulatory potential of c-aAbs is now well documented. Here, we investigated the hypothesis that c-aAbs affects inflammatory, immunoregulatory and injury-related processes and hence the clinical outcome of haematopoietic stem cell transplantation (HSCT). C-aAbs against IL-1α, IL-6, IL-10, IFNα, IFNγ and GM-CSF were measured in 131 HSCT recipients before and after (days + 7, + 14, + 28) HSCT and tested for associations with 33 different plasma biomarkers, leukocyte subsets, platelets and clinical outcomes, including engraftment, GvHD and infections. We found that c-aAb levels were stable over the course of HSCT, including at high titres, with few individuals seeming to acquire high-titre levels of c-aAbs. Both patients with stable and those with acquired high-titre c-aAb levels displayed significant differences in biomarker concentrations and blood cell counts pre-HSCT and at day 28, and the trajectories of these variables varied over the course of HSCT. No clinical outcomes were associated with high-titre c-aAbs. In this first study of c-aAbs in HSCT patients, we demonstrated that high-titre levels of c-aAb may both persist and emerge in patients over the course of HSCT and may be associated with altered immune biomarkers and cell profiles.
细胞因子特异性自身抗体(c-aAbs)是内源性免疫缺陷的一个新兴领域,c-aAbs 的免疫调节潜力现在已有充分的记录。在这里,我们研究了这样一个假设,即 c-aAbs 是否会影响炎症、免疫调节和损伤相关过程,从而影响造血干细胞移植(HSCT)的临床结果。在 HSCT 前后(+7 天、+14 天、+28 天),我们测量了 131 名 HSCT 受者的抗白细胞介素 1α、白细胞介素 6、白细胞介素 10、IFNα、IFNγ 和 GM-CSF 的 c-aAbs,并测试了它们与 33 种不同的血浆生物标志物、白细胞亚群、血小板和临床结果(包括植入、移植物抗宿主病和感染)之间的关联。我们发现,c-aAb 水平在 HSCT 过程中保持稳定,包括在高滴度时,很少有个体似乎获得高滴度的 c-aAbs。具有稳定和获得高滴度 c-aAb 水平的患者在 HSCT 前和第 28 天的生物标志物浓度和血细胞计数方面均有显著差异,这些变量的轨迹在 HSCT 过程中发生了变化。高滴度 c-aAbs 与任何临床结果均无关。在这项对 HSCT 患者 c-aAbs 的首次研究中,我们证明了高滴度的 c-aAb 可能在患者的 HSCT 过程中持续存在并出现,并可能与改变的免疫生物标志物和细胞特征有关。