Zorn Emmanuel, See Sarah B
Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA.
Curr Opin Organ Transplant. 2017 Feb;22(1):8-13. doi: 10.1097/MOT.0000000000000376.
Antibody-mediated rejection (ABMR), especially in its chronic manifestation, is increasingly recognized as a leading cause of late graft loss following solid organ transplantation. In recent years, autoantibodies have emerged as a significant component of the humoral response to allografts alongside anti-human leukocyte antigen antibodies. These include polyreactive antibodies also known as natural antibodies (Nabs) secreted by innate B cells. A hallmark of Nabs is their capacity to bind altered self such as oxidized lipids on apoptotic cells. This review provides an overview of these overlooked antibodies and their implication in the pathophysiology of ABMR.
New evidence reported in the past few years support a contribution of immunoglobulin (Ig) G Nabs to ABMR. Serum IgG Nabs levels are significantly higher in patients with ABMR compared with control kidney transplant recipients with stable graft function. Pretransplant IgG Nabs are also associated with ABMR and late graft loss. IgG Nabs are almost exclusively of the IgG1 and IgG3 subclasses and have the capacity to activate complement.
In conclusion, Nabs are important elements in host immune responses to solid organ grafts. The recent description of their implication in ABMR and late kidney graft loss warrants further investigation into their pathogenic potential.
抗体介导的排斥反应(ABMR),尤其是其慢性表现形式,日益被认为是实体器官移植后晚期移植物丢失的主要原因。近年来,自身抗体已成为同种异体移植物体液反应中的重要组成部分,与抗人类白细胞抗原抗体并存。这些抗体包括由先天B细胞分泌的多反应性抗体,也称为天然抗体(Nabs)。Nabs的一个特点是它们能够结合改变的自身成分,如凋亡细胞上的氧化脂质。本综述概述了这些被忽视的抗体及其在ABMR病理生理学中的意义。
过去几年报道的新证据支持免疫球蛋白(Ig)G Nabs对ABMR有影响。与移植肾功能稳定的对照肾移植受者相比,ABMR患者的血清IgG Nabs水平显著更高。移植前的IgG Nabs也与ABMR和晚期移植物丢失有关。IgG Nabs几乎完全属于IgG1和IgG3亚类,并且有激活补体的能力。
总之,Nabs是宿主对实体器官移植物免疫反应中的重要元素。最近关于它们在ABMR和晚期肾移植丢失中的作用的描述,值得进一步研究它们的致病潜力。