Lefaucheur Carmen, Louis Kevin, Philippe Aurélie, Loupy Alexandre, Coates P Toby
Paris Translational Research Center for Organ Transplantation, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR)-S970, Université de Paris, Paris, France; Kidney Transplant Department, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Kidney Transplant Department, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Human Immunology and Immunopathology, Institut National de la santé et de la recherche médicale Unité Mixte de Recherche (UMR)-976, Université de Paris, Paris, France.
Kidney Int. 2021 Oct;100(4):787-798. doi: 10.1016/j.kint.2021.04.044. Epub 2021 Jun 26.
The major medical advances in our knowledge of the human leukocyte antigen (HLA) system have allowed us to uncover several gaps in our understanding of alloimmunity. Although the non-HLA system has long sparked the interest of the transplant community, recognition of the role of immunity to non-HLA antigenic targets has only emerged recently. In this review, we will provide a comprehensive summary of the paradigm-changing concept of immunity to the non-HLA angiotensin II type 1 receptor (AT1R), discovered by Duška Dragun et al., that began from careful bedside clinical observations, to validated detection of anti-AT1R antibodies and lead to clinical intervention. This scientific approach has also allowed the recognition of broader pathogenicity of anti-AT1R antibodies across multiple organ transplants and in other human diseases, the integration of both non-HLA and HLA systems to understand their immunologic effects on organ allografts, and the identification of future directions for therapeutic intervention to modulate immunity to AT1R. Rationally designed successful interventions to target AT1R system provide an exemplar for other non-HLA antibodies to cross borders between medical specialties, will generate new avenues in translational research beyond transplantation, and will foster the development of new and reliable tools to improve our understanding of non-HLA immunity and ultimately allow us to improve patient care.
我们对人类白细胞抗原（HLA）系统的认识取得了重大医学进展，这使我们发现了自身在同种免疫理解上的一些空白。尽管非HLA系统长期以来一直引发移植界的兴趣，但对非HLA抗原靶点免疫作用的认识直到最近才出现。在这篇综述中，我们将全面总结由杜什卡·德拉贡等人发现的针对非HLA血管紧张素II 1型受体（AT1R）免疫这一改变范式的概念，该概念始于细致的床边临床观察，经过抗AT1R抗体的验证检测，最终走向临床干预。这种科学方法还使人们认识到抗AT1R抗体在多种器官移植及其他人类疾病中的更广泛致病性，整合非HLA和HLA系统以了解它们对器官同种异体移植的免疫作用，并确定调节对AT1R免疫的治疗干预的未来方向。针对AT1R系统合理设计的成功干预措施为其他非HLA抗体跨越医学专科界限提供了范例，将在移植以外的转化研究中开辟新途径，并将促进开发新的可靠工具，以增进我们对非HLA免疫的理解，最终改善患者护理。
