Laboratoire d’Anatomie Pathologique, Hôpital Européen Georges Pompidou, APHP, Paris, France.
J Am Soc Nephrol. 2011 May;22(5):975-83. doi: 10.1681/ASN.2010070777. Epub 2011 Apr 14.
In biopsies of renal allografts, arteriosclerosis is often more severe than expected based on the age of the donor, even without a history of rejection vasculitis. To determine whether preformed donor-specific antibodies (DSAs) may contribute to the severity of arteriosclerosis, we examined protocol biopsies from patients with (n=40) or without (n=59) DSA after excluding those with any evidence of vasculitis. Among DSA-positive patients, arteriosclerosis significantly progressed between month 3 and month 12 after transplant (mean Banff cv score 0.65 ± 0.11 to 1.12 ± 0.10, P=0.014); in contrast, among DSA-negative patients, we did not detect a statistically significant progression during the same timeframe (mean Banff cv score 0.65 ± 0.11 to 0.81 ± 0.10, P=not significant). Available biopsies at later time points supported a rate of progression of arteriosclerosis in DSA-negative patients that was approximately one third that in DSA-positive patients. Accelerated arteriosclerosis was significantly associated with peritubular capillary leukocytic infiltration, glomerulitis, subclinical antibody-mediated rejection, and interstitial inflammation. In conclusion, these data support the hypothesis that donor-specific antibodies dramatically accelerate post-transplant progression of arteriosclerosis.
在肾移植活检中，即使没有排斥性血管炎病史，动脉硬化的严重程度也常常超出根据供体年龄所预期的程度。为了确定预先形成的供体特异性抗体（DSA）是否可能导致动脉硬化的严重程度增加，我们排除了有任何血管炎证据的患者后，检查了 DSA 阳性（n=40）或 DSA 阴性（n=59）患者的方案活检。在 DSA 阳性患者中，移植后 3 个月至 12 个月间动脉硬化明显进展（平均 Banff cv 评分从 0.65±0.11 增加至 1.12±0.10，P=0.014）；相比之下，在 DSA 阴性患者中，在相同的时间段内，我们没有检测到统计学上的显著进展（平均 Banff cv 评分从 0.65±0.11 增加至 0.81±0.10，P=无显著差异）。在后续时间点获得的可用活检支持 DSA 阴性患者动脉硬化进展的速度约为 DSA 阳性患者的三分之一。动脉硬化的加速进展与肾小管毛细血管白细胞浸润、肾小球肾炎、亚临床抗体介导的排斥反应和间质炎症显著相关。总之，这些数据支持供体特异性抗体可显著加速移植后动脉硬化进展的假说。
