Yao Yue Ying, Lee Dennis K, Jarvi Stephanie, Farshadi Marjan, Sheng Minzhi, Mar Sara, Nevo Ori, Leong Hon S
Department of Medical Biophysics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L7, Canada.
Biological Sciences Platform, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
Bioengineering (Basel). 2023 Jan 12;10(1):110. doi: 10.3390/bioengineering10010110.
Limited graft availability is a constant clinical concern. Hence, the umbilical cord (UC) is an attractive alternative to autologous grafts. The UC is an inexhaustible tissue source, and its removal is harmless and part of standard of care after the birth of the baby. Minimal information exists regarding the immunological profile of a whole UC when it is considered to be used as a tissue graft. We aimed to characterize the localization and levels of class I human leukocyte antigens (HLAs) to understand the allogenicity of the UC. Additionally, HLA-E and HLA-G are putative immunosuppressive antigens that are abundant in placenta, but their profiles in UC whole tissue are unclear.
The UC as a whole expresses a relatively low but ubiquitous level of HLA-ABC and significant levels of HLA-G and HLA-E.
Healthy patients with no known pregnancy-related complications were approached for informed consent. UCs at term and between 12 and 19 weeks were collected to compare HLA profiles by gestational age. Formalin-fixed paraffin-embedded tissues were sectioned to 5 µm and immunohistochemically stained with a pan-HLA-ABC, two HLA-G-specific, or an HLA-E-specific antibody.
HLA-ABC was consistently found present in UCs. HLA-ABC was most concentrated in the UC vessel walls and amniotic epithelium but more dispersed in the Wharton's Jelly. HLA-E had a similar localization pattern to HLA-ABC in whole UC tissues at both gestational ages, but its protein level was lower. HLA-G localization and intensity were poor in all UC tissues analyzed, but additional analyses by Western immunoblot and mass spectrometry revealed a low level of HLA-G in the UC.
The UC may address limitations of graft availability. Rather than the presence of HLA-G, the immunosuppressive properties of the UC are more likely due to the abundance of HLA-E and the interaction known to occur between HLA-E and HLA-ABC. The co-localization of HLA-E and HLA-ABC suggests that HLA-E is likely presenting HLA-ABC leader peptides to immune cells, which is known to have a primarily inhibitory effect.
移植物供应有限一直是临床关注的问题。因此，脐带是自体移植物的一种有吸引力的替代物。脐带是一种取之不尽的组织来源，其采集无害，且是婴儿出生后标准护理的一部分。关于将整个脐带用作组织移植物时的免疫特征，现有信息极少。我们旨在确定I类人类白细胞抗原（HLA）的定位和水平，以了解脐带的同种异体反应性。此外，HLA-E和HLA-G是推测具有免疫抑制作用的抗原，在胎盘中含量丰富，但它们在脐带全组织中的特征尚不清楚。
作为一个整体，脐带表达相对较低但普遍存在的HLA-ABC水平，以及显著水平的HLA-G和HLA-E。
向无已知妊娠相关并发症的健康患者征求知情同意。收集足月及12至19周的脐带，以比较不同孕周的HLA特征。将福尔马林固定石蜡包埋组织切成5μm切片，并用泛HLA-ABC、两种HLA-G特异性或一种HLA-E特异性抗体进行免疫组织化学染色。
在脐带中始终发现有HLA-ABC。HLA-ABC最集中于脐带血管壁和羊膜上皮，但在华通胶中分布更分散。在两个孕周的脐带全组织中，HLA-E的定位模式与HLA-ABC相似，但其蛋白水平较低。在所有分析的脐带组织中，HLA-G的定位和强度均较差，但通过Western免疫印迹和质谱进行的进一步分析显示脐带中存在低水平的HLA-G。
脐带可能解决移植物供应的限制问题。脐带的免疫抑制特性更可能是由于HLA-E的丰富以及已知HLA-E与HLA-ABC之间发生的相互作用，而不是由于HLA-G的存在。HLA-E和HLA-ABC的共定位表明，HLA-E可能将HLA-ABC前导肽呈递给免疫细胞，已知这主要具有抑制作用。
