Colella Marcos Paulo, Morini Beatriz Corey, Niemann Fernanda, Lopes Matheus Rodrigues, Saad Sara Olalla, Favaro Patricia
Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brazil.
Universidade Federal do Vale do São Francisco (Univasf), Paulo Afonso, BA, Brazil.
Hematol Transfus Cell Ther. 2023 Jul-Sep;45(3):324-329. doi: 10.1016/j.htct.2022.05.005. Epub 2022 Jun 17.
Chronic graft-versus-host disease (cGvHD) not only remains the main cause of late mortality after allogeneic hematopoietic cell transplant, but also has the capacity of causing severe organ impairment in those who survive. The Notch, a highly conserved ligand-receptor pathway, is involved in many immunological processes, including inflammatory and regulatory responses. Recently, mouse models have shown that the blockage of canonical Notch signaling prevents GvHD.
Due to the lack of data on the Notch pathway in human chronic GvHD, we sought to study the expression of NOTCH components in primary samples of patients who received allo-HCT and presented active cGvHD or a long-term clinical tolerance to cGvHD.
Our results showed a significantly lower expression of NOTCH components in both groups that received allo-HCT, independently of their cGvHD status, when compared to healthy controls.
Moreover, there were no differences in gene expression levels between the active cGvHD and clinically tolerant groups. To our knowledge, this is one of the first studies performed in human primary samples and our data indicate that much remains to be learned regarding NOTCH signaling as a new regulator of GvHD.
慢性移植物抗宿主病（cGvHD）不仅仍然是异基因造血细胞移植后晚期死亡的主要原因，而且还会导致存活者出现严重的器官损害。Notch是一种高度保守的配体-受体途径，参与许多免疫过程，包括炎症和调节反应。最近，小鼠模型表明，经典Notch信号通路的阻断可预防移植物抗宿主病。
由于缺乏人类慢性移植物抗宿主病中Notch途径的数据，我们试图研究接受异基因造血干细胞移植（allo-HCT）并表现出活动性cGvHD或对cGvHD具有长期临床耐受性的患者原代样本中NOTCH成分的表达。
我们的结果显示，与健康对照组相比，接受allo-HCT的两组患者中NOTCH成分的表达均显著降低，且与他们的cGvHD状态无关。
此外，活动性cGvHD组和临床耐受组之间的基因表达水平没有差异。据我们所知，这是在人类原代样本中进行的首批研究之一，我们的数据表明，关于Notch信号作为移植物抗宿主病的新调节因子，仍有许多有待了解之处。
