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抗体介导性排斥反应的诊断与治疗新进展

Novelties in diagnostics and therapy of antibody mediated rejection.

作者信息

Dragun Duska, Rudolph Birgit

机构信息

Department of Nephrology and Intensive Care Medicine, Charite Campus Virchow Clinic, Augustenburger Platz 1, 13353 Berlin, Germany.

出版信息

Nephrol Dial Transplant. 2007 Sep;22 Suppl 8:viii50-viii53. doi: 10.1093/ndt/gfm647.

Abstract

Antibody mediated rejection (AMR) is becoming an increasing challenge in renal allotransplantation. AMR is usually associated with profound allograft dysfunction and inferior allograft survival. In the era of refined crossmatch-techniques and improved solid-phase assays, hyperacute rejections in presensitized patients are less common. Majority of AMRs occur due to de novo production of donor specific antibodies. AMR appears to stand for a spectrum of histologic changes paralled with immunohistochemical positivity for C4d along peritubular capillaries. Removal of antibodies with plasmapheresis or immunoadsorption in combination with neutralizing and immunomodulatory intravenous immunoglobulin are therapy standards in majority of transplant centers worldwide. The addition of anti-CD20 (rituximab) with the aim to reduce the number of B-cells may offer advantage in some cases. Apart from donor specific HLA-antibodies, non-HLA antibodies reacting to arterial antigens have been speculated to be responsible for rejections in some patients. More precise definition of antigen targets for non-HLA antibodies is emerging. The analysis of the subtle mechanistic and diagnostic differences among rejection subtypes will help to identify patients at particular risk and improve outcome of AMR.

摘要

抗体介导的排斥反应(AMR)在同种异体肾移植中日益成为一项挑战。AMR通常与严重的移植肾功能不全及移植肾较差的存活情况相关。在精细的交叉配型技术和改进的固相检测时代,致敏患者中的超急性排斥反应已较少见。大多数AMR是由于供体特异性抗体的重新产生所致。AMR似乎代表了一系列组织学改变,同时伴有肾小管周围毛细血管C4d免疫组化阳性。在全球大多数移植中心,采用血浆置换或免疫吸附清除抗体,并联合使用中和及免疫调节性静脉注射免疫球蛋白是治疗标准。在某些情况下,添加抗CD20(利妥昔单抗)以减少B细胞数量可能具有优势。除了供体特异性HLA抗体外,已推测某些对动脉抗原起反应的非HLA抗体是导致部分患者排斥反应的原因。非HLA抗体抗原靶点的更精确界定正在出现。对排斥反应亚型之间细微的机制和诊断差异进行分析,将有助于识别具有特定风险的患者并改善AMR的治疗结果。

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