Filippone Edward J, Farber John L
Division of Nephrology, Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
Department of Pathology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
Transplantation. 2021 Nov 1;105(11):e181-e190. doi: 10.1097/TP.0000000000003797.
Histologic antibody-mediated rejection (hAMR) is defined as a kidney allograft biopsy satisfying the first 2 Banff criteria for diagnosing AMR: tissue injury and evidence of current/recent antibody interaction with the endothelium. In approximately one-half of such cases, circulating human leukocyte antigen (HLA) donor-specific antibodies (DSA) are not detectable by current methodology at the time of biopsy. Some studies indicated a better prognosis for HLA-DSA-negative cases of hAMR compared to those with detectable HLA-DSA, whereas others found equally poor survival compared to hAMR-negative cases. We reviewed the literature regarding the pathophysiology of HLA-DSA-negative hAMR. We find 3 nonmutually exclusive possibilities: (1) HLA-DSA are involved, but just not detected; (2) non-HLA-DSA (allo or autoantibodies) are pathogenically involved; and/or (3) antibody-independent NK cell activation is mediating the process through "missing-self" or other activating mechanisms. These possibilities are discussed in detail. Recommendations regarding the approach to such patients are made. Clearly, more research is necessary regarding the measurement of non-HLA antibodies, recipient/donor NK cell genotyping, and the use of antibody reduction therapy or other immunosuppression in any subset of patients with HLA-DSA-negative hAMR.
组织学抗体介导的排斥反应（hAMR）定义为肾移植活检符合诊断AMR的前两条班夫标准：组织损伤以及当前/近期抗体与内皮细胞相互作用的证据。在大约一半的此类病例中，活检时采用当前方法检测不到循环中的人类白细胞抗原（HLA）供体特异性抗体（DSA）。一些研究表明，与可检测到HLA-DSA的hAMR病例相比，HLA-DSA阴性的hAMR病例预后更好，而另一些研究则发现其生存率与hAMR阴性病例同样差。我们回顾了关于HLA-DSA阴性hAMR病理生理学的文献。我们发现三种并非相互排斥的可能性：（1）HLA-DSA参与其中，但只是未被检测到；（2）非HLA-DSA（同种或自身抗体）在发病机制上起作用；和/或（3）抗体非依赖性自然杀伤细胞激活通过“缺失自我”或其他激活机制介导这一过程。对这些可能性进行了详细讨论。针对此类患者的治疗方法提出了建议。显然，对于非HLA抗体的检测、受体/供体自然杀伤细胞基因分型以及在任何HLA-DSA阴性hAMR患者亚组中使用抗体清除疗法或其他免疫抑制措施，还需要进行更多研究。
