Section of Nephrology, Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana.
Clin J Am Soc Nephrol. 2018 Jan 6;13(1):182-192. doi: 10.2215/CJN.00700117. Epub 2017 Apr 26.
Donor-specific antibodies have become an established biomarker predicting antibody-mediated rejection. Antibody-mediated rejection is the leading cause of graft loss after kidney transplant. There are several phenotypes of antibody-mediated rejection along post-transplant course that are determined by the timing and extent of humoral response and the various characteristics of donor-specific antibodies, such as antigen classes, specificity, antibody strength, IgG subclasses, and complement binding capacity. Preformed donor-specific antibodies in sensitized patients can trigger hyperacute rejection, accelerated acute rejection, and early acute antibody-mediated rejection. donor-specific antibodies are associated with late acute antibody-mediated rejection, chronic antibody-mediated rejection, and transplant glomerulopathy. The pathogeneses of antibody-mediated rejection include not only complement-dependent cytotoxicity, but also complement-independent pathways of antibody-mediated cellular cytotoxicity and direct endothelial activation and proliferation. The novel assay for complement binding capacity has improved our ability to predict antibody-mediated rejection phenotypes. C1q binding donor-specific antibodies are closely associated with acute antibody-mediated rejection, more severe graft injuries, and early graft failure, whereas C1q nonbinding donor-specific antibodies correlate with subclinical or chronic antibody-mediated rejection and late graft loss. IgG subclasses have various abilities to activate complement and recruit effector cells through the Fc receptor. Complement binding IgG3 donor-specific antibodies are frequently associated with acute antibody-mediated rejection and severe graft injury, whereas noncomplement binding IgG4 donor-specific antibodies are more correlated with subclinical or chronic antibody-mediated rejection and transplant glomerulopathy. Our in-depth knowledge of complex characteristics of donor-specific antibodies can stratify the patient's immunologic risk, can predict distinct phenotypes of antibody-mediated rejection, and hopefully, will guide our clinical practice to improve the transplant outcomes.
供体特异性抗体已成为预测抗体介导排斥反应的既定生物标志物。抗体介导的排斥反应是肾移植后移植物丢失的主要原因。在移植后过程中，存在几种抗体介导排斥反应的表型，这些表型由体液反应的时间和程度以及供体特异性抗体的各种特征决定，例如抗原类别、特异性、抗体强度、IgG 亚类和补体结合能力。致敏患者中的预先形成的供体特异性抗体可引发超急性排斥反应、加速急性排斥反应和早期急性抗体介导的排斥反应。供体特异性抗体与晚期急性抗体介导的排斥反应、慢性抗体介导的排斥反应和移植肾小球病有关。抗体介导的排斥反应的发病机制不仅包括补体依赖性细胞毒性，还包括补体非依赖性的抗体介导的细胞毒性和直接内皮激活和增殖途径。新型补体结合能力检测可提高我们预测抗体介导排斥反应表型的能力。C1q 结合供体特异性抗体与急性抗体介导排斥反应、更严重的移植物损伤和早期移植物失败密切相关，而 C1q 非结合供体特异性抗体与亚临床或慢性抗体介导排斥反应和晚期移植物丢失相关。IgG 亚类具有通过 Fc 受体激活补体和募集效应细胞的不同能力。补体结合 IgG3 供体特异性抗体常与急性抗体介导排斥反应和严重的移植物损伤相关，而非补体结合 IgG4 供体特异性抗体与亚临床或慢性抗体介导排斥反应和移植肾小球病的相关性更高。我们对供体特异性抗体复杂特征的深入了解可以对患者的免疫风险进行分层，可以预测不同的抗体介导排斥反应表型，并有望指导我们的临床实践以改善移植结果。
