Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Transplantation. 2010 May 15;89(9):1088-94. doi: 10.1097/TP.0b013e3181d368f1.
BACKGROUND.: Anti-human leukocyte antigen antibodies (a-HLA) cause graft injury identified by C4d in peritubular capillaries. We investigated whether a-HLA relate to episodes of C4d negative acute rejection (AR). METHODS.: We analyzed 878 kidney recipients transplanted from January 2000 to December 2006. Pretransplant, 36% of these crossmatch negative recipients had a-HLA measured by solid phase assays. RESULTS.: AR occurred in 154 patients (18%) and 11 of them (9.4%) were C4d+. Forty-six percent of ARs were diagnosed by protocol biopsy. The risk of C4d-AR was increased in patients with a-HLA class I with donor specificity (DSA-I) (hazard ratio=1.519; confidence interval, 1.02-2.26; P=0.039). DSA-II were not associated with an increased risk of C4d-AR. The relationship between DSA-I and C4d-AR was independent of recipient age, BK nephropathy, and HLA mismatches. Compared with DSA-, in DSA+ recipients C4d-AR were most often histologically "borderline." DSA+ was associated with capillaritis in the biopsy (glomerulitis, 6.1% vs. 32%, P=0.003; peritubular capillaritis: 13% vs. 40%, P=0.0009). Compared with no AR, C4d-AR with capillaritis was associated with reduced graft survival (hazard ratio=4.164; confidence interval, 1.763-9.832; P=0.001), independent of other variables. This association was observed even in the cases of borderline AR. CONCLUSIONS.: DSA-I increases the risk of C4d-AR. The presence of DSA-I or II is associated with capillaritis during AR. Capillaritis is associated with reduced graft survival.
抗人类白细胞抗原抗体（a-HLA）导致移植肾组织中管周毛细血管 C4d 阳性的移植物损伤。我们研究了 a-HLA 是否与 C4d 阴性急性排斥反应（AR）的发生有关。方法：我们分析了 2000 年 1 月至 2006 年 12 月期间接受肾移植的 878 例患者。在移植前，36%的这些交叉配型阴性的患者通过固相分析检测到 a-HLA。结果：154 例患者（18%）发生了 AR，其中 11 例（9.4%）为 C4d+。46%的 AR 通过方案活检诊断。具有供体特异性（DSA-I）的 a-HLA 类 I 患者发生 C4d-AR 的风险增加（风险比=1.519；95%置信区间，1.02-2.26；P=0.039）。DSA-II 与 C4d-AR 发生风险增加无关。DSA-I 与 C4d-AR 之间的关系与受者年龄、BK 肾病和 HLA 错配无关。与 DSA-相比，在 DSA+患者中，C4d-AR 组织学上常为“边界性”。DSA+与活检中的血管炎相关（肾小球肾炎，6.1%比 32%，P=0.003；肾小管周围毛细血管炎，13%比 40%，P=0.0009）。与无 AR 相比，伴有血管炎的 C4d-AR 与移植物存活率降低相关（风险比=4.164；95%置信区间，1.763-9.832；P=0.001），与其他变量无关。即使在边界性 AR 中也观察到了这种相关性。结论：DSA-I 增加了 C4d-AR 的风险。DSA-I 或 II 的存在与 AR 期间的血管炎相关。血管炎与移植物存活率降低相关。
