Krishnan Nithya, Briggs David
Department of Renal and Transplant Medicine, Institute of Cardiometabolic Medicine, University of Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom.
Institute of Community and Health Care, Coventry University, Coventry, United Kingdom.
Indian J Nephrol. 2024 Jul-Aug;34(4):291-296. doi: 10.25259/ijn_325_23. Epub 2024 Apr 29.
Potential kidney transplant patients with HLA-specific antibodies have reduced access to transplantation. Their harmful effects are mediated by the Fc portion of IgG, including activation of the complement system and Fc receptor-initiated cytotoxic processes by circulating leucocytes. Avoiding antibody incompatibility is the conventional approach, but for some patients this can mean extended waiting times, or even no chance of a transplant if there are no alternative, compatible donors. For these cases, pretransplant antibody removal may provide access to transplantation. Plasmapheresis is currently used to achieve this, with acceptable outcome results, but the process can take days to reduce the antibody levels to a safe level, so has limited use for deceased donors. There is now an alternative, in the form of an IgG-digesting enzyme, Imlifidase, which can be administered for IgG inactivation. Imlifidase cleaves human IgG, separating the antigen-binding part, F(ab') from Fc. Typically, within six hours of dosing, most, if not all, of the circulating IgG has been inactivated, allowing safe transplantation from a previously incompatible donor. For deceased donor transplantation, where minimizing cold ischaemia is critical, this six-hour delay before implantation should be manageable, with the compatibility testing processes adjusted to accommodate the treatment. This agent has been used successfully in phase 2 clinical trials, with good short to medium term outcomes. While a donation rate that matches demand may be one essential answer to providing universal access to kidney transplantation, this is currently unrealistic. IgG inactivation, using Imlifidase, is, however, a realistic and proven alternative.
具有HLA特异性抗体的潜在肾移植患者获得移植的机会减少。其有害作用由IgG的Fc部分介导，包括补体系统的激活以及循环白细胞通过Fc受体引发的细胞毒性过程。避免抗体不相容是传统方法，但对一些患者来说，这可能意味着等待时间延长，或者如果没有其他相容的供体，甚至没有移植的机会。对于这些情况，移植前去除抗体可能提供移植机会。目前使用血浆置换来实现这一点，结果可以接受，但该过程可能需要数天才能将抗体水平降低到安全水平，因此对已故供体的使用有限。现在有一种替代方法，即一种可用于使IgG失活的IgG消化酶——伊米苷酶。伊米苷酶可切割人IgG，将抗原结合部分F(ab')与Fc分离。通常，给药后6小时内，大部分（如果不是全部）循环IgG已失活，从而可以安全地接受来自先前不相容供体的移植。对于已故供体移植，尽量减少冷缺血至关重要，植入前6小时的延迟应该是可以控制的，同时调整相容性检测流程以适应治疗。该药物已在2期临床试验中成功使用，短期至中期结果良好。虽然捐赠率与需求相匹配可能是实现普遍肾移植的一个重要答案，但目前这并不现实。然而，使用伊米苷酶使IgG失活是一种现实且已得到验证的替代方法。
