Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Transplantation. 2010 May 27;89(10):1239-46. doi: 10.1097/TP.0b013e3181d72091.
Chronic humoral rejection (CHR) is a major complication after kidney transplantation. The cause of CHR is currently unknown. Autoantibodies have often been reported in kidney transplant recipients alongside antidonor human leukocyte antigen antibodies. Yet, the lack of comprehensive studies has limited our understanding of this autoimmune component in the pathophysiology of CHR.
By using a series of ELISA and immunocytochemistry assays, we assessed the development of autoantibodies in 25 kidney transplant recipients with CHR and 25 patients with stable graft function. We also compared the reactivity of five CHR and five non-CHR patient sera with 8027 recombinant human proteins using protein microarrays.
We observed that a majority of CHR patients, but not non-CHR control patients, had developed antibody responses to one or several autoantigens at the time of rejection. Protein microarray assays revealed a burst of autoimmunity at the time of CHR. Remarkably, microarray analysis showed minimal overlap between profiles, indicating that each CHR patient had developed autoantibodies to a unique set of antigenic targets.
The breadth of autoantibody responses, together with the absence of consensual targets, suggests that these antibody responses result from systemic B-cell deregulation.
慢性体液性排斥反应（CHR）是肾移植后的主要并发症。目前尚不清楚 CHR 的病因。肾移植受者常伴有抗供体人类白细胞抗原抗体的自身抗体。然而，缺乏全面的研究限制了我们对 CHR 病理生理学中这种自身免疫成分的理解。
通过一系列 ELISA 和免疫细胞化学检测，我们评估了 25 例 CHR 肾移植受者和 25 例稳定移植物功能患者的自身抗体的发展情况。我们还使用蛋白质微阵列比较了 5 例 CHR 和 5 例非 CHR 患者血清与 8027 个重组人类蛋白的反应性。
我们观察到大多数 CHR 患者（而非非 CHR 对照组患者）在排斥反应时已对一种或多种自身抗原产生抗体反应。蛋白质微阵列检测显示 CHR 时出现了自身免疫反应的爆发。值得注意的是，微阵列分析显示图谱之间几乎没有重叠，表明每个 CHR 患者都针对一组独特的抗原靶标产生了自身抗体。
广泛的自身抗体反应，加上没有共识的靶标，表明这些抗体反应是由于系统性 B 细胞失调所致。
