de Graav Gretchen N, Hesselink Dennis A, Dieterich Marjolein, Kraaijeveld Rens, Douben Hannie, de Klein Annelies, Roelen Dave L, Weimar Willem, Roodnat Joke I, Clahsen-van Groningen Marian C, Baan Carla C
1 Department of Internal Medicine, Section Transplantation and Nephrology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. 2 Department of Clinical Genetics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. 3 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands. 4 Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
Transplantation. 2016 May;100(5):1111-9. doi: 10.1097/TP.0000000000001004.
Belatacept has been associated with an increased acute rejection rate after kidney transplantation. This case report sheds light on the possible immunological mechanisms underlying this phenomenon by analyzing the immunological mechanisms in patient serum, peripheral blood mononuclear cells, rejected kidney tissue, and graft infiltrating cells.
A 61-year-old woman treated with belatacept, who received her first kidney transplant from her husband was admitted with an acute, vascular rejection 56 days after transplantation which necessitated a transplantectomy. Histology and immunohistochemistry were performed on biopsy and explant tissue. CD86 expression on peripheral monocytes was assessed. Using Ficoll density methods, peripheral blood, and graft infiltrating lymphocytes were isolated and phenotyped.
The explant showed a vascular rejection (Banff ACR grade III) and a perivascular infiltrate mostly consisting of T cells. No evidence for antibody-mediated rejection was found. In contrast to the peripheral blood monocytes, CD86 was still expressed by part of the mononuclear cells in the explant.Isolated graft cells were mostly CCR7-CD45RO+ effector memory CD4 and CD8 T cells (60-70%). CD28-positive as CD28-negative T cells were present in the explant, showing a great IFN-γ production capacity and expressing granzyme B.
We postulate that this glucocorticoid-resistant cellular rejection occurring under belatacept was predominantly mediated by cytotoxic memory T cells, which are less susceptible to costimulatory blockade by belatacept, or resulted from incomplete CD80/86 blockade at the tissue level.
贝拉西普与肾移植后急性排斥反应率增加有关。本病例报告通过分析患者血清、外周血单核细胞、移植肾组织和移植物浸润细胞中的免疫机制，揭示了这一现象潜在的免疫机制。
一名61岁接受贝拉西普治疗的女性患者，接受了来自其丈夫的首次肾移植，在移植后56天因急性血管排斥反应入院，需要进行移植肾切除术。对活检组织和切除组织进行了组织学和免疫组织化学检查。评估外周单核细胞上CD86的表达。使用Ficoll密度法分离外周血和移植物浸润淋巴细胞并进行表型分析。
切除的移植肾显示血管排斥反应（Banff ACR III级）和血管周围浸润，主要由T细胞组成。未发现抗体介导的排斥反应证据。与外周血单核细胞不同，切除组织中的部分单核细胞仍表达CD86。分离出的移植物细胞大多为CCR7-CD45RO+效应记忆CD4和CD8 T细胞（60-70%）。切除组织中存在CD28阳性和CD28阴性T细胞，显示出强大的干扰素-γ产生能力并表达颗粒酶B。
我们推测，在贝拉西普治疗下发生的这种糖皮质激素抵抗性细胞排斥反应主要由细胞毒性记忆T细胞介导，这些细胞对贝拉西普的共刺激阻断不太敏感，或者是由于组织水平上CD80/86阻断不完全所致。
