Transplant Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Am J Transplant. 2013 Oct;13(10):2590-600. doi: 10.1111/ajt.12394. Epub 2013 Aug 6.
Antibody mediated rejection (AMR) is associated with a variety of graft-reactive antibodies following kidney transplant. To characterize these antibodies, we immortalized 107 B cell clones from a patient with AMR. In a previous study, we showed that six clones were reacting to multiple self-antigens as well as to HLA and MICA for two of them, thus displaying a pattern of polyreactivity. We show here that all six polyreactive clones also reacted to apoptotic but not viable cells. More generally we observed a nearly perfect overlap between polyreactivity and reactivity to apoptotic cells. Functionally, polyreactive antibodies can activate complement, resulting in the deposition of C3d and C4d at the surface of target cells. Testing the serum of 88 kidney transplant recipients revealed a significantly higher IgG reactivity to apoptotic cells in AMR patients than in patients with stable graft function. Moreover, total IgG purified from AMR patients had increased complement activating properties compared to IgG from non-AMR patients. Overall, our studies show the development of polyreactive antibodies cross-reactive to apoptotic cells during AMR. Further studies are now warranted to determine their contribution to the detection of C4d in graft biopsies as well as their role in the pathophysiology of AMR.
抗体介导的排斥反应（AMR）与肾移植后多种移植物反应性抗体有关。为了描述这些抗体，我们从 AMR 患者中永生了 107 个 B 细胞克隆。在之前的研究中，我们表明，其中六个克隆可以识别多种自身抗原以及 HLA 和 MICA，对于其中两个克隆，表现出多反应性。我们在这里表明，所有六个多反应性克隆也可以识别凋亡细胞，但不能识别存活细胞。更普遍的是，我们观察到多反应性和对凋亡细胞的反应之间几乎完全重叠。在功能上，多反应性抗体可以激活补体，导致 C3d 和 C4d 在靶细胞表面沉积。对 88 名肾移植受者的血清进行检测，结果表明 AMR 患者对凋亡细胞的 IgG 反应性明显高于稳定移植物功能的患者。此外，从 AMR 患者中纯化的总 IgG 比非 AMR 患者的 IgG 具有更高的补体激活特性。总的来说，我们的研究表明，在 AMR 期间会产生针对凋亡细胞的多反应性抗体。现在需要进一步研究来确定它们对移植活检中 C4d 检测的贡献，以及它们在 AMR 病理生理学中的作用。
