免疫抑制剂停药后抗人类白细胞抗原和抗血管紧张素 II 型 1 型受体抗体与肝移植纤维化的关系。

Association of anti-human leukocyte antigen and anti-angiotensin II type 1 receptor antibodies with liver allograft fibrosis after immunosuppression withdrawal.

机构信息

1 Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 2 Department of Gastroenterological Surgery, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan. 3 Terasaki Foundation Laboratory, Los Angeles, CA. 4 Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan. 5 Address correspondence to: Hidenori Ohe, M.D., Ph.D., Terasaki Foundation Laboratory, 11570 W. Olympic Blvd, Los Angeles, CA 90064.

出版信息

Transplantation. 2014 Nov 27;98(10):1105-11. doi: 10.1097/TP.0000000000000185.

DOI:10.1097/TP.0000000000000185

PMID:24914568

Abstract

BACKGROUND

Many pediatric patients who receive a living-donor liver transplant undergo withdrawal of immunosuppression (IS). For them, the high incidence of long-term progressive graft fibrosis is of particular concern.

METHODS

We conducted a cross-sectional study including 81 pediatric patients who underwent IS withdrawal after living-donor liver transplant at Kyoto University Hospital and whose serum samples and pathological data could be obtained during the analysis period. We examined the association of donor-specific anti-human leukocyte antigen (HLA) antibody (DSA) and angiotensin II type 1 receptor antibody (anti-AT1R Ab) with posttransplant graft fibrosis. Normalized mean fluorescence intensity (MFI) 5,000 or higher and anti-AT1R Ab concentrations 17 U/mL or higher were both considered high level. The patients were classified into an advanced fibrosis group (AFG) (Ishak score ≥ 3) and a control group (CG) (Ishak score ≤ 2).

RESULTS

Only one patient demonstrated DSA class I. Among those who demonstrated DSA class II, more AFG patients than CG patients demonstrated high-level mean fluorescence intensity, although the difference was not significant (64% vs. 39%; P=0.053). The incidence of high-level DSA-DRB1, however, was significantly higher in the AFG than that in the CG (40% vs. 4%; P<0.001), but there was no significant difference in DSA-DQB1 or DSA-DRB345. High-level anti-AT1R Ab was significantly more frequent in the AFG than in the CG (65% vs. 36%; P=0.02). All patients with both high-level DSA-DRB1 and high-level anti-AT1R Ab were found to have advanced fibrosis (P<0.001).

CONCLUSION

Anti-AT1R Ab and DSA-DRB1 may be candidates as biomarkers of graft fibrosis; both HLA and non-HLA immunity may be involved in graft fibrosis after IS withdrawal.

摘要

背景

许多接受活体供肝移植的儿科患者需要停用免疫抑制剂（IS）。对他们来说，长期进行性移植物纤维化的高发生率尤其令人担忧。

方法

我们进行了一项横断面研究，纳入了 81 名在京都大学医院接受活体供肝移植后停用 IS 的儿科患者，并且在分析期间可以获得他们的血清样本和病理数据。我们研究了供体特异性抗人类白细胞抗原（HLA）抗体（DSA）和血管紧张素 II 型 1 受体抗体（抗 AT1R Ab）与移植后移植物纤维化的关系。将供体特异性抗人类白细胞抗原（HLA）抗体（DSA）和血管紧张素 II 型 1 受体抗体（抗 AT1R Ab）的归一化平均荧光强度（MFI）≥5000 和抗 AT1R Ab 浓度≥17 U/mL 均视为高水平。将患者分为晚期纤维化组（AFG）（Ishak 评分≥3）和对照组（CG）（Ishak 评分≤2）。

结果

只有 1 名患者存在 I 类 DSA。在存在 II 类 DSA 的患者中，尽管差异无统计学意义（64%比 39%；P=0.053），但 AFG 患者中高水平 MFI 的比例高于 CG 患者。然而，AFG 患者中高水平 DSA-DRB1 的发生率明显高于 CG 患者（40%比 4%；P<0.001），但 DSA-DQB1 或 DSA-DRB345 无显著差异。AFG 患者中高水平抗 AT1R Ab 的比例明显高于 CG 患者（65%比 36%；P=0.02）。所有同时存在高水平 DSA-DRB1 和高水平抗 AT1R Ab 的患者均存在晚期纤维化（P<0.001）。