Toyoda M, Thomas D, Ahn G, Kahwaji J, Mirocha J, Chu M, Vo A, Suviolahti E, Ge S, Jordan S C
Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Transpl Infect Dis. 2015 Dec;17(6):838-47. doi: 10.1111/tid.12465.
Desensitization (DES) with intravenous immunoglobulin (IVIG) + rituximab is effective, safe, and increases the transplantation rate in human leukocyte antigen-sensitized patients. However, reports of progressive multifocal leukoencephalopathy (PML) caused by JC polyomavirus (JCPyV) in autoimmune patients treated with rituximab is concerning. Here, we report on the JCPyV viremia and PML status in kidney transplant patients with/without DES (non-DES).
In total 1195 and 699 DNA samples from plasma in 117 DES (78% lymphocyte-depleting [LyD] induction) and 100 non-DES patients (45% LyD), respectively, were submitted for JCPyV-polymerase chain reaction. Results were compared in both groups.
No patients in either DES or non-DES developed PML or presented with any neurological symptoms. The JCPyV viremia rate was similar in DES and non-DES patients (3/117 vs. 9/100, P = 0.07). The JCPyV levels were low (median peak levels, 1025 copies/mL) and JCPyV viremia was observed only once during the study period in most patients. All 3 DES patients with JCPyV(+) received 1 dose rituximab and no DES patients with >1 dose rituximab showed JCPyV(+). All 3 JCPyV(+) DES patients received LyD induction, while only 2 of 9 JCPyV(+) non-DES patients did so, and the remaining 7 received non-LyD or no induction. JCPyV in leukocyte was mostly negative in DES and non-DES patients. Immunosuppression in patients with or without JCPyV(+) was similar. BK polyomavirus viremia was observed more commonly in patients with JCPyV(+) than in those without (P < 0.02).
Patients with IVIG + rituximab DES followed by transplantation with LyD induction and additional rituximab rarely show JCPyV viremia and appear at low risk for PML.
静脉注射免疫球蛋白（IVIG）联合利妥昔单抗进行脱敏治疗（DES）有效、安全，且能提高人类白细胞抗原致敏患者的移植率。然而，接受利妥昔单抗治疗的自身免疫性疾病患者中，由JC多瘤病毒（JCPyV）引起进行性多灶性白质脑病（PML）的报道令人担忧。在此，我们报告了接受或未接受DES（非DES）的肾移植患者的JCPyV病毒血症和PML状况。
分别从117例接受DES治疗（78%采用淋巴细胞清除[LyD]诱导方案）的患者和100例未接受DES治疗（45%采用LyD诱导方案）的患者血浆中提取1195份和699份DNA样本，进行JCPyV聚合酶链反应检测。比较两组结果。
DES组和非DES组均无患者发生PML或出现任何神经系统症状。DES组和非DES组的JCPyV病毒血症发生率相似（3/117 vs. 9/100，P = 0.07）。JCPyV水平较低（中位峰值水平为1025拷贝/mL），且大多数患者在研究期间仅观察到一次JCPyV病毒血症。所有3例JCPyV（+）的DES患者均接受了1剂利妥昔单抗，而接受>1剂利妥昔单抗的DES患者均未出现JCPyV（+）。所有3例JCPyV（+）的DES患者均接受了LyD诱导，而9例JCPyV（+）的非DES患者中只有2例接受了LyD诱导，其余7例接受了非LyD诱导或未接受诱导。DES组和非DES组患者白细胞中的JCPyV大多为阴性。JCPyV（+）和JCPyV（-）患者的免疫抑制情况相似。JCPyV（+）患者中BK多瘤病毒血症的发生率高于JCPyV（-）患者（P < 0.02）。
接受IVIG + 利妥昔单抗DES治疗、随后进行LyD诱导移植并追加利妥昔单抗的患者很少出现JCPyV病毒血症，发生PML的风险较低。
