Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, CB2 0XY, Cambridge, UK.
Curr Opin Immunol. 2010 Oct;22(5):669-81. doi: 10.1016/j.coi.2010.08.018.
Donor-specific alloantibodies (DSA) mediate hyperacute and acute antibody-mediated rejection (AMR), which can lead to early graft damage and loss, and are also associated with chronic AMR and reduced long-term graft survival. Such alloantibodies can be generated by previous exposure to major histocompatibility (MHC) antigens (usually via blood transfusions, previous allografts or pregnancy) or can occur de novo after transplantation. Recent studies also suggest that non-MHC antibodies, including those recognising major histocompatibility complex class I-related chain A (MICA), MICB, vimentin, angiotensin II type I receptor may also have an adverse impact on allograft outcomes. In this review, we consider how the dose, route and context of antigen exposure influences DSA induction and describe factors which control the generation, maintenance and survival of alloantibody-producing plasma cells. Finally, we discuss the implications of these variables on therapeutic approaches to DSA.
供者特异性抗体(DSA)介导超急性和急性抗体介导的排斥反应(AMR),可导致早期移植物损伤和丢失,也与慢性 AMR 和降低长期移植物存活率相关。这些同种异体抗体可由先前暴露于主要组织相容性(MHC)抗原(通常通过输血、先前的同种异体移植物或妊娠)产生,也可在移植后新出现。最近的研究还表明,非 MHC 抗体,包括识别主要组织相容性复合体 I 类相关链 A(MICA)、MICB、波形蛋白、血管紧张素 II 型 1 受体的抗体,也可能对移植物结局产生不良影响。在这篇综述中,我们考虑了抗原暴露的剂量、途径和背景如何影响 DSA 的诱导,并描述了控制产生、维持和存活产生同种异体抗体的浆细胞的因素。最后,我们讨论了这些变量对 DSA 治疗方法的影响。