Transplant Center, The First Hospital of Jilin University, Changchun, China; Transplant Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Am J Transplant. 2014 Jul;14(7):1581-91. doi: 10.1111/ajt.12763. Epub 2014 Jun 16.
Preexisting serum antibodies have long been associated with graft loss in transplant recipients. While most studies have focused on HLA-specific antibodies, the contribution of non-HLA-reactive antibodies has been largely overlooked. We have recently characterized mAbs secreted by B cell clones derived from kidney allograft recipients with rejection that bind to apoptotic cells. Here, we assessed the presence of such antibodies in pretransplant serum from 300 kidney transplant recipients and examined their contribution to the graft outcomes. Kaplan-Meier survival analysis revealed that patients with high pretransplant IgG reactivity to apoptotic cells had a significantly increased rate of late graft loss. The effect was only apparent after approximately 1 year posttransplant. Moreover, the association between pretransplant IgG reactivity to apoptotic cells and graft loss was still significant after excluding patients with high reactivity to HLA. This reactivity was almost exclusively mediated by IgG1 and IgG3 with complement fixing and activating properties. Overall, our findings support the view that IgG reactive to apoptotic cells contribute to presensitization. Taking these antibodies into consideration alongside anti-HLA antibodies during candidate evaluation would likely improve the transplant risk assessment.
预先存在的血清抗体长期以来一直与移植受者的移植物丢失有关。虽然大多数研究都集中在 HLA 特异性抗体上，但非 HLA 反应性抗体的贡献在很大程度上被忽视了。我们最近对来自发生排斥反应的肾移植受者的 B 细胞克隆分泌的 mAb 进行了表征，这些 mAb 可以与凋亡细胞结合。在这里，我们评估了 300 名肾移植受者的移植前血清中是否存在此类抗体，并检查了它们对移植物结局的贡献。Kaplan-Meier 生存分析显示，具有高预存 IgG 对凋亡细胞反应性的患者晚期移植物丢失率显著增加。这种影响仅在移植后约 1 年时才明显出现。此外，在排除了对 HLA 高反应性的患者后，移植前 IgG 对凋亡细胞的反应性与移植物丢失之间的关联仍然显著。这种反应性几乎完全由具有补体结合和激活特性的 IgG1 和 IgG3 介导。总的来说，我们的研究结果支持这样一种观点，即针对凋亡细胞的 IgG 反应有助于预致敏。在候选者评估过程中，将这些抗体与抗 HLA 抗体一起考虑，可能会提高移植风险评估的准确性。
