Department of Surgery Department of Pathology, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Am J Transplant. 2012 Nov;12(11):3047-60. doi: 10.1111/j.1600-6143.2012.04237.x. Epub 2012 Sep 4.
Despite improvement in early outcome, rejection particularly chronic allograft enteropathy continues to be a major barrier to long-term visceral engraftment. The potential role of donor specific antibodies (DSA) was examined in 194 primary adult recipients. All underwent complement-dependent lymphocytotoxic crossmatch (CDC-XM) with pre- and posttransplant solid phase HLA-DSA assay in 156 (80%). Grafts were ABO-identical with random HLA-match. Liver was included in 71 (37%) allografts. Immunosuppression was tacrolimus-based with antilymphocyte recipient pretreatment in 150 (77%). CDC-XM was positive in 55 (28%). HLA-DSA was detectable before transplant in 49 (31%) recipients with 19 continuing to have circulating antibodies. Another 19 (18%) developed de novo DSA. Ninety percent of patients with preformed DSA harbored HLA Class-I whereas 74% of recipients with de novo antibodies had Class-II. Gender, age, ABO blood-type, cold ischemia, splenectomy and allograft type were significant DSA predictors. Preformed DSA significantly (p < 0.05) increased risk of acute rejection. Persistent and de novo HLA-DSA significantly (p < 0.001) increased risk of chronic rejection and associated graft loss. Inclusion of the liver was a significant predictor of better outcome (p = 0.004, HR = 0.347) with significant clearance of preformed antibodies (p = 0.04, OR = 56) and lower induction of de novo DSA (p = 0.07, OR = 24). Innovative multifaceted anti-DSA strategies are required to further improve long-term survival particularly of liver-free allografts.
尽管早期结果有所改善，但排斥反应，特别是慢性同种异体肠病，仍然是长期内脏移植物植入的主要障碍。在 194 名成人原发性受者中检查了供体特异性抗体 (DSA) 的潜在作用。所有患者均进行了补体依赖性淋巴细胞毒性交叉配型 (CDC-XM)，并在 156 例（80%）患者中进行了移植前和移植后固相 HLA-DSA 检测。肝脏移植 71 例（37%），所有移植物均为 ABO 相同，HLA 随机匹配。免疫抑制为他克莫司为基础，150 例（77%）患者接受抗淋巴细胞受体预处理。CDC-XM 阳性 55 例（28%）。49 例（31%）受者移植前可检测到 HLA-DSA，其中 19 例持续存在循环抗体，另外 19 例（18%）出现新的 DSA。90%的预存 DSA 患者携带 HLA Ⅰ类，而 74%的新抗体患者携带Ⅱ类。性别、年龄、ABO 血型、冷缺血、脾切除术和移植物类型是 DSA 的显著预测因素。预存 DSA 显著（p < 0.05）增加了急性排斥反应的风险。持续性和新出现的 HLA-DSA 显著（p < 0.001）增加了慢性排斥反应和相关移植物丢失的风险。包含肝脏是改善预后的显著预测因素（p = 0.004，HR = 0.347），可以显著清除预存抗体（p = 0.04，OR = 56），并降低新出现的 DSA 的诱导（p = 0.07，OR = 24）。需要创新的多方面抗 DSA 策略，以进一步提高长期生存率，特别是无肝移植物的生存率。
