Early effects of first-line treatment with anti-interleukin-6 receptor antibody tocilizumab for chronic active antibody-mediated rejection in kidney transplantation
Early effects of first-line treatment with anti-interleukin-6 receptor antibody tocilizumab for chronic active antibody-mediated rejection in kidney transplantation
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DOI：
10.1111/ctr.13908
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发表时间：
2020-06-16
影响因子：
2.1
通讯作者：
Biancone, Luigi
中科院分区：
文献类型：
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作者：
Lavacca, Antonio;Presta, Roberto;Biancone, Luigi
慢性活性抗体介导的排斥反应（cAMR）是晚期同种异体移植失败的主要决定因素。利妥昔单抗/免疫球蛋白（IVIg）+血浆置换（PLEX）在cAMR治疗中显示出有争议的结果。托珠单抗（TCZ）是一种人源化抗白细胞介素6受体抗体，最近已被用作对利妥昔单抗/IVIg/PLEX无反应的患者的补救治疗，具有良好的结局。TCZ是否“本身”起作用或需要先前治疗的启动效应目前尚不清楚。方法15例cAMR患者接受TCZ一线治疗，中位随访时间20.7个月。结果尽管大多数患者在诊断时患有晚期移植物肾小球病（TG）（60%为cg 3），但在随访期间肾小球滤过率和蛋白尿稳定，供者特异性抗体显著降低。6个月后的方案活检显示微血管炎症显著改善，无TG、C4d沉积或IF/TA进展。基因表达和免疫荧光分析表明，上调的三个基因（TJP-1，AKR 1C 3和CASK）参与足细胞，系膜和肾小管的恢复。结论：Tocilizumab作为cAMR的一线治疗方法与早期血清学和组织学改善以及功能稳定相关，即使在晚期TG中，这表明单独使用TCZ并避免不必要的既往免疫抑制剂的作用。
Introduction Chronic active antibody-mediated rejection (cAMR) is a major determinant of late allograft failure. Rituximab/immunoglobulins (IVIg) + plasma exchange (PLEX) showed controversial results in cAMR treatment. Tocilizumab (TCZ), a humanized anti-interleukin 6 receptor antibody, has been recently used as rescue therapy in patients non-responsive to rituximab/IVIg/PLEX with favorable outcomes. Whether TCZ acts "per se" or requires a priming effect from previous treatments is currently unknown. Methods Fifteen patients with cAMR were treated with TCZ as a first-line therapy and followed for a median time of 20.7 months. Results Despite the majority of patients experiencing advanced transplant glomerulopathy (TG) at diagnosis (60% with cg3), glomerular filtration rate and proteinuria stabilized during the follow-up, with a significant reduction in donor-specific antibodies. Protocol biopsies after 6 months demonstrated significant amelioration of microvascular inflammation and no TG, C4d deposition, or IF/TA progression. Gene-expression and immunofluorescence analysis showed upregulation of three genes (TJP-1, AKR1C3, and CASK) involved in podocyte, mesangial, and tubular restoration. Conclusion Tocilizumab adopted as a first-line approach in cAMR was associated with early serological and histological improvements and functional stabilization even in advanced TG, suggesting a role for the use of TCZ alone with the avoidance of unnecessary previous immunosuppressants.