Jordan Stanley C, Pescovitz Mark D
Transplant Immunology Laboratory, Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California 90048, USA.
Clin J Am Soc Nephrol. 2006 May;1(3):421-32. doi: 10.2215/CJN.01651105. Epub 2006 Apr 12.
Much attention has been placed recently on transplantation in highly HLA-sensitized patients. In attempts to remove these antibodies and enable successful transplantation, several novel approaches have been developed. These include intravenous Ig (IVIg), mycophenolate mofetil, sirolimus, alemtuzumab, protein A immunoabsorption, and rituximab. IVIg has emerged as a very effective agent when used alone in high dose or when used in low dose and combined with plasmapheresis. Although alemtuzumab has been used to eliminated B cells, it fails to prevent antibody-mediated rejection and therefore probably is not suitable for desensitization. Rituximab, a B cell-specific antibody, seems to be safe and to have some efficacy as a sole agent in elimination of alloantibodies but most likely will require combination therapy with IVIg or other agents. Newer agents, such as humanized anti-CD20, are being developed. Despite the great interest in the problem of allosensitization, with one notable exception, there is a major deficiency in controlled clinical trials, the conduct of which should be a focus for the near future.
最近，高度HLA致敏患者的移植受到了广泛关注。为了去除这些抗体并实现成功移植，人们开发了几种新方法。这些方法包括静脉注射免疫球蛋白（IVIg）、霉酚酸酯、西罗莫司、阿仑单抗、蛋白A免疫吸附和利妥昔单抗。单独使用高剂量IVIg或低剂量IVIg并联合血浆置换时，IVIg已成为一种非常有效的药物。尽管阿仑单抗已被用于清除B细胞，但它无法预防抗体介导的排斥反应，因此可能不适合用于脱敏治疗。利妥昔单抗是一种B细胞特异性抗体，作为单一药物在消除同种异体抗体方面似乎是安全的且有一定疗效，但很可能需要与IVIg或其他药物联合治疗。新型药物，如人源化抗CD20正在研发中。尽管对同种致敏问题有很大兴趣，但除了一个显著例外，对照临床试验存在重大缺陷，而开展对照临床试验应是近期的重点。
