Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria.
Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria; Cardiac Surgery Laboratory, Medical University of Vienna, Vienna, Austria.
J Allergy Clin Immunol. 2019 Jan;143(1):335-345.e12. doi: 10.1016/j.jaci.2018.06.034. Epub 2018 Aug 9.
Donor-specific antibodies of the IgG isotype are measured routinely for diagnostic purposes in renal transplant recipients and are associated with antibody-mediated rejection and long-term graft loss.
This study aimed to investigate whether MHC-specific antibodies of the IgE isotype are induced during allograft rejection.
Anti-MHC/HLA IgE levels were measured in sera of mice grafted with skin or heart transplants from various donor strains and in sera of kidney transplant patients with high levels of HLA IgG. Mediator release was triggered in vitro by stimulating basophils that were coated with murine or human IgE-positive serum, respectively, with specific recombinant MHC/HLA antigens. Kidney tissue samples obtained from organ donors were analyzed by using flow cytometry for cells expressing the high-affinity receptor for IgE (FcεRI).
Donor MHC class I- and MHC class II-specific IgE was found on acute rejection of skin and heart grafts in several murine strain combinations, as well as during chronic antibody-mediated heart graft rejection. Anti-HLA IgE, including donor HLA class I and II specificities, was identified in a group of sensitized transplant recipients. Murine and human anti-MHC/HLA IgE triggered mediator release in coated basophils on stimulation with specific MHC/HLA antigens. HLA-specific IgE was not linked to atopy, and allergen-specific IgE present in allergic patients did not cross-react with HLA antigens. FcεRI cells were found in the human renal cortex and medulla and provide targets for HLA-specific IgE.
These results demonstrate that MHC/HLA-specific IgE develops during an alloresponse and is functional in mediating effector mechanisms.
在肾移植受者中，常规检测 IgG 同种异体抗体用于诊断，并与抗体介导的排斥反应和长期移植物丢失有关。
本研究旨在探讨同种异体移植排斥过程中是否会产生 IgE 同种异体抗体。
测量来自不同供体株系的皮肤或心脏移植小鼠的血清中抗 MHC/HLA IgE 水平，以及 HLA IgG 水平较高的肾移植患者的血清中抗 MHC/HLA IgE 水平。通过分别用特异性重组 MHC/HLA 抗原刺激包被有鼠或人 IgE 阳性血清的嗜碱性粒细胞，在体外触发介质释放。使用流式细胞术分析从器官供体获得的肾组织样本，以分析表达高亲和力 IgE 受体（FcεRI）的细胞。
在几种小鼠品系组合的皮肤和心脏移植物急性排斥反应中，以及在慢性抗体介导的心脏移植物排斥反应中，发现了供体 MHC Ⅰ类和 MHC Ⅱ类特异性 IgE。在一组致敏的移植受者中，发现了抗 HLA IgE，包括供体 HLA Ⅰ类和Ⅱ类特异性。抗 MHC/HLA IgE 可触发包被嗜碱性粒细胞在特异性 MHC/HLA 抗原刺激下释放介质。HLA 特异性 IgE 与特应性无关，过敏性患者中的过敏原特异性 IgE 与 HLA 抗原无交叉反应。FcεRI 细胞存在于人类肾皮质和髓质中，为 HLA 特异性 IgE 提供了靶标。
这些结果表明，MHC/HLA 特异性 IgE 在同种异体反应过程中产生，并具有介导效应机制的功能。
