Gül-Klein Safak, Hegermann Henriette, Röhle Robert, Schmelzle Moritz, Tacke Frank, Schöning Wenzel, Öllinger Robert, Dziodzio Tomasz, Maier Patrick, Plewe Julius M, Horst David, Sauer Igor Maximilian, Pratschke Johann, Lachmann Nils, Eurich Dennis
Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany.
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Berlin, Germany.
J Inflamm Res. 2021 Jun 23;14:2697-2712. doi: 10.2147/JIR.S307778. eCollection 2021.
Donor-specific antibodies (DSA) against donor human leukocyte antigen after liver transplantation, which are associated with histological changes, have been widely studied with respect to their sustained impact on transplant function. However, their long-term impact after liver transplantation remains unclear.
We performed a cross-sectional analysis from June 2016 to July 2017 that included all patients who presented themselves for scheduled follow-up after receiving a liver transplantation between September 1989 and December 2016. In addition to a liver protocol biopsy, patients were screened for human leukocyte antigen antibodies (HLAab) and donor-specific antibodies. Subsequently, the association between human leukocyte antigen antibodies, donor-specific antibodies, histologic and clinical features, and immunosuppression was analyzed.
Analysis for human leukocyte antigen antibodies and donor-specific antibodies against donor human leukocyte antigen was performed for 291 and 271 patients. A significant association between higher inflammation grades and the presence of human leukocyte antigen antibodies and donor-specific antibodies was detected, while fibrosis stages remained unaffected. These results were confirmed by multivariate logistic regression for inflammation showing a significant increase for presence of human leukocyte antigen antibodies and donor-specific antibodies (OR: 4.43; 95% CI: 1.67-12.6; p=0.0035). Furthermore, the use of everolimus in combination with tacrolimus was significantly associated with the status of negative human leukocyte antigen antibodies and donor-specific antibodies. Viral etiology for liver disease, hepatocellular carcinoma (HCC) and higher steatosis grades of the graft were significantly associated with a lower rate of human leukocyte antigen antibodies. The impact of human leukocyte antigen antibodies and donor-specific antibodies against donor human leukocyte antigen was associated with higher levels of laboratory parameters, such as transaminases and bilirubin.
Donor-specific antibodies against donor human leukocyte antigen are associated with histological and biochemical graft inflammation after liver transplantation, while fibrosis seems to be unaffected. Future studies should validate these findings for longer observation periods and specific subgroups.
肝移植后针对供体人类白细胞抗原的供体特异性抗体（DSA）与组织学变化相关，其对移植功能的持续影响已得到广泛研究。然而，它们在肝移植后的长期影响仍不清楚。
我们在2016年6月至2017年7月进行了一项横断面分析，纳入了1989年9月至2016年12月接受肝移植后前来进行定期随访的所有患者。除了进行肝脏方案活检外，还对患者进行了人类白细胞抗原抗体（HLAab）和供体特异性抗体筛查。随后，分析了人类白细胞抗原抗体、供体特异性抗体、组织学和临床特征以及免疫抑制之间的关联。
对291例和271例患者进行了针对供体人类白细胞抗原的人类白细胞抗原抗体和供体特异性抗体分析。检测到较高炎症分级与人类白细胞抗原抗体和供体特异性抗体的存在之间存在显著关联，而纤维化阶段未受影响。炎症的多因素逻辑回归证实了这些结果，显示人类白细胞抗原抗体和供体特异性抗体的存在显著增加（比值比：4.43；95%置信区间：1.67 - 12.6；p = 0.0035）。此外，依维莫司与他克莫司联合使用与人类白细胞抗原抗体和供体特异性抗体阴性状态显著相关。肝病的病毒病因、肝细胞癌（HCC）以及移植物较高的脂肪变性分级与人类白细胞抗原抗体的较低发生率显著相关。针对供体人类白细胞抗原的人类白细胞抗原抗体和供体特异性抗体与较高水平的实验室参数（如转氨酶和胆红素）相关。
肝移植后针对供体人类白细胞抗原的供体特异性抗体与移植肝的组织学和生化炎症相关，而纤维化似乎未受影响。未来的研究应在更长的观察期和特定亚组中验证这些发现。
