NYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Nat Rev Nephrol. 2018 Sep;14(9):558-570. doi: 10.1038/s41581-018-0039-x.
The human major histocompatibility complex is a family of genes that encodes HLAs, which have a crucial role in defence against foreign pathogens and immune surveillance of tumours. In the context of transplantation, HLA molecules are polymorphic antigens that comprise an immunodominant alloreactive trigger for the immune response, resulting in rejection. Remarkable advances in knowledge and technology in the field of immunogenetics have considerably enhanced the safety of transplantation. However, access to transplantation among individuals who have become sensitized as a result of previous exposure to alloantigens is reduced proportional to the breadth of their sensitization. New approaches for crossing the HLA barrier in transplantation using plasmapheresis, intravenous immunoglobulin and kidney paired donation have been made possible by the relative ease with which even low levels of anti-HLA antibodies can now be detected and tracked. The development of novel protocols for the induction of tolerance and new approaches to immunomodulation was also facilitated by advances in HLA technology. Here, we review the progress made in understanding HLAs that has enabled organ transplantation to become a life-saving endeavour that is accessible even for sensitized patients. We also discuss novel approaches to desensitization, immunomodulation and tolerance induction that have the potential to further improve transplantation access and outcomes.
人类主要组织相容性复合体是一组编码 HLA 的基因，HLA 在抵御外来病原体和肿瘤免疫监测方面发挥着关键作用。在移植的背景下，HLA 分子是多态性抗原，构成免疫反应的主要同种异体反应触发因素，导致排斥反应。免疫遗传学领域的知识和技术的显著进步大大提高了移植的安全性。然而，由于先前接触同种异体抗原而致敏的个体获得移植的机会与他们致敏的广度成比例降低。通过现在更容易检测和跟踪即使是低水平的抗 HLA 抗体，使用血浆置换、静脉注射免疫球蛋白和配对供肾等方法来跨越移植中的 HLA 障碍成为可能。新型诱导耐受方案和新型免疫调节方法的发展也得益于 HLA 技术的进步。在这里，我们回顾了在理解 HLA 方面取得的进展，这些进展使器官移植成为一项拯救生命的努力，即使是致敏患者也可以接受。我们还讨论了潜在的脱敏、免疫调节和耐受诱导的新方法，这些方法有可能进一步改善移植的机会和结果。
