Utsumi Masashi, Takaki Akinobu, Umeda Yuzo, Koike Kazuko, Napier Stephanie C, Watanabe Nobukazu, Shinoura Susumu, Yoshida Ryuichi, Nobuoka Daisuke, Yasunaka Tetsuya, Oto Takahiro, Araki Motoo, Yamamoto Kazuhide, Fujiwara Toshiyoshi, Yagi Takahito
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Ann Transplant. 2017 Mar 24;22:156-165. doi: 10.12659/aot.900494.
BACKGROUND Human leukocyte antigen (HLA) mismatch is a characteristic feature of post-orthotopic liver transplantation (OLT) hepatitis C. To investigate the importance of donor HLA-restricted immune cells in post-OLT hepatitis C recurrence, we analyzed the frequency of donor chimerism and the clinical course of post-OLT hepatitis C. MATERIAL AND METHODS We analyzed peripheral blood chimerism in 11 HCV-reinfected patients with post-HLA mismatched OLT. Patients were divided into 2 groups: the OLT chronic hepatitis C (CHC) group (n=8), exhibiting active hepatitis C recurrence; and the OLT-persistently normal ALT (PNALT) group (n=3), without active hepatitis. Chimerism was analyzed by flow cytometry using donor-specific anti-HLA antibodies in peripheral blood mononuclear cells from 1-100 days after OLT. Kidney (n=7) and lung (n=7) transplant recipients were also analyzed for comparison. As immune cells from the donor liver might contribute to post-OLT chimerism, the characteristics of perfusates from donor livers (n=10) were analyzed and defined. RESULTS Donor-derived cells were frequently observed in liver and lung transplant recipients. The frequency of donor-derived cells from the B cell subset was significantly higher in peripheral blood from OLT-CHC group than in that of the OLT-PNALT group. B cells, however, were not the predominant subset in the perfusates, indicating that inflow of donor-derived cells alone did not cause the chimerism. CONCLUSIONS Chimerism of B cells is frequent in liver transplant patients with early recurrence of hepatitis C. We propose that monitoring of early chimerism could facilitate early detection of chronic hepatitis C recurrence, although we need more cases to investigate.
背景 人类白细胞抗原（HLA）不匹配是原位肝移植（OLT）后丙型肝炎的一个特征。为了研究供体HLA限制性免疫细胞在OLT后丙型肝炎复发中的重要性，我们分析了供体嵌合体的频率以及OLT后丙型肝炎的临床病程。材料与方法 我们分析了11例HLA不匹配的OLT后丙型肝炎病毒再感染患者的外周血嵌合体情况。患者分为两组：OLT慢性丙型肝炎（CHC）组（n = 8），表现为丙型肝炎复发活跃；OLT持续正常丙氨酸转氨酶（PNALT）组（n = 3），无丙型肝炎活动。在OLT后1至100天，使用供体特异性抗HLA抗体通过流式细胞术分析外周血单个核细胞中的嵌合体情况。还分析了肾移植受者（n = 7）和肺移植受者（n = 7）作为对照。由于来自供体肝脏的免疫细胞可能促成OLT后的嵌合体，因此分析并确定了10例供体肝脏灌洗液的特征。结果 在肝移植和肺移植受者中经常观察到供体来源的细胞。OLT-CHC组外周血中B细胞亚群的供体来源细胞频率明显高于OLT-PNALT组。然而，B细胞不是灌洗液中的主要亚群，这表明仅供体来源细胞的流入不会导致嵌合体。结论 丙型肝炎早期复发的肝移植患者中B细胞嵌合体很常见。我们建议监测早期嵌合体有助于早期发现慢性丙型肝炎复发，尽管我们需要更多病例进行研究。
