Acute graft‐versus‐host disease (GVHD) is a rare but frequently lethal complication after solid organ transplantation. GVHD occurs in unduly immunocompromised hosts but requires the escalation of immunosuppression, which does not discriminate between host and donor cells. In contrast, donor‐targeted therapy would ideally mitigate graft‐versus‐host reactivity while sparing recipient immune functions. We report two children with end‐stage renal disease and severe primary immune deficiency (Schimke syndrome) who developed severe steroid‐resistant acute GVHD along with full and sustained donor T cell chimerism after isolated kidney transplantation. Facing a therapeutic dead end, we used a novel strategy based on the adoptive transfer of anti‐HLA donor‐specific antibodies (DSAs) through the transfusion of highly selected plasma. After approval by the appropriate regulatory authority, an urgent nationwide search was launched among more than 3800 registered blood donors with known anti‐HLA sensitization. Adoptively transferred DSAs bound to and selectively depleted circulating donor T cells. The administration of DSA‐rich plasma was well tolerated and notably did not induce antibody‐mediated rejection of the renal allografts. Acute GVHD symptoms promptly resolved in one child. This report provides a proof of concept for a highly targeted novel therapeutic approach for solid organ transplantation–associated GVHD.

中文翻译：

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供体靶向血清疗法作为 HLA 不匹配肾移植后类固醇耐药性急性 GVHD 的挽救疗法。

急性移植物抗宿主病 (GVHD) 是实体器官移植后罕见但经常致命的并发症。GVHD 发生在免疫功能不全的宿主中，但需要免疫抑制的升级，这不会区分宿主和供体细胞。相比之下，供体靶向治疗可以理想地减轻移植物抗宿主反应，同时保留受体免疫功能。我们报告了两名患有终末期肾病和严重原发性免疫缺陷（Schimke 综合征）的儿童，他们在孤立的肾移植后发展为严重的类固醇耐药性急性 GVHD 以及完全和持续的供体 T 细胞嵌合体。面对治疗的死胡同，我们使用了一种新策略，该策略基于通过输注高度选择的血浆过继转移抗 HLA 供体特异性抗体 (DSA)。经有关监管机构批准后，在 3800 多名已知抗 HLA 致敏的注册献血者中展开了一项紧急全国搜索。过继转移的 DSAs 结合并选择性地耗尽循环供体 T 细胞。施用富含 DSA 的血浆具有良好的耐受性，并且值得注意的是不会诱导抗体介导的同种异体移植肾排斥反应。一名儿童的急性 GVHD 症状迅速消失。该报告为实体器官移植相关 GVHD 的高度靶向新型治疗方法提供了概念证明。施用富含 DSA 的血浆具有良好的耐受性，并且值得注意的是不会诱导抗体介导的同种异体移植肾排斥反应。一名儿童的急性 GVHD 症状迅速消失。该报告为实体器官移植相关 GVHD 的高度靶向新型治疗方法提供了概念证明。施用富含 DSA 的血浆具有良好的耐受性，并且值得注意的是不会诱导抗体介导的同种异体移植肾排斥反应。一名儿童的急性 GVHD 症状迅速消失。该报告为实体器官移植相关 GVHD 的高度靶向新型治疗方法提供了概念证明。