Nanmoku Koji, Shinzato Takahiro, Kubo Taro, Shimizu Toshihiro, Yagisawa Takashi
Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital, Shimotsuke, Japan.
Transplant Direct. 2019 Jun 27;5(7):e467. doi: 10.1097/TXD.0000000000000907. eCollection 2019 Jul.
Rituximab is used widely for desensitization in ABO-incompatible and donor-specific antibody-positive kidney transplantation. However, data about the effects of individual differences in rituximab-induced B-cell suppression on antibody-mediated rejection (AMR) remain unknown. We aimed to assess the association between CD19-positive rate and AMR following rituximab administration after kidney transplantation.
Overall, 42 patients who underwent rituximab therapy for pretransplant desensitization in ABO-incompatible (n = 33) and donor-specific antibody-positive (n = 15) kidney transplantation were observed retrospectively. To predict AMR incidence, the peripheral blood CD19-positive rate was determined and classified into short- and long-acting groups. AMR incidence, allograft function, complications, and rituximab dose were compared.
Eight patients (19%) had AMR within 39.2 months after transplantation. The CD19-positive rate cutoff value to predict AMR incidence was 4.4%, 6.4%, and 7.7% at 6, 12, and 18 months after transplantation, respectively. When comparing the short- and long-acting groups stratified according to the CD19-positive rate cutoff value, AMR incidence was significantly higher in the short-acting group than in the long-acting group at 6 (71.4% vs 8.6%), 12 (70.0% vs 3.1%), and 18 (58.3% vs 3.3%) months after transplantation. The CD19-positive rate for all patients with AMR exceeded the cutoff value 6, 12, or 18 months. Conversely, serum creatinine level, tacrolimus trough-level, cytomegalovirus antigenemia-positive rate, neutropenia incidence rate, and total dose of rituximab before transplantation showed no significant differences between the 2 groups.
The risk of AMR was higher in patients with short-term B-cell suppression following rituximab administration. Additional rituximab administration after transplantation may prevent AMR in patients with a CD19-positive rate higher than the cutoff value.
利妥昔单抗广泛用于ABO血型不相容和供体特异性抗体阳性肾移植的脱敏治疗。然而,关于利妥昔单抗诱导的B细胞抑制的个体差异对抗体介导的排斥反应(AMR)影响的数据仍不清楚。我们旨在评估肾移植后给予利妥昔单抗后CD19阳性率与AMR之间的关联。
总体上,对42例在ABO血型不相容(n = 33)和供体特异性抗体阳性(n = 15)肾移植中接受利妥昔单抗治疗进行移植前脱敏的患者进行回顾性观察。为预测AMR发生率,测定外周血CD19阳性率并分为短效和长效组。比较AMR发生率、移植肾功能、并发症和利妥昔单抗剂量。
8例患者(19%)在移植后39.2个月内发生AMR。移植后6、12和18个月预测AMR发生率时CD19阳性率的临界值分别为4.4%、6.4%和7.7%。根据CD19阳性率临界值分层比较短效和长效组时,移植后6个月(71.4%对8.6%)、12个月(70.0%对3.1%)和18个月(58.3%对3.3%)短效组的AMR发生率显著高于长效组。所有发生AMR的患者的CD19阳性率在6、12或18个月时超过临界值。相反,两组之间血清肌酐水平、他克莫司谷浓度、巨细胞病毒血症阳性率、中性粒细胞减少发生率和移植前利妥昔单抗总剂量无显著差异。
利妥昔单抗给药后短期B细胞抑制的患者发生AMR的风险较高。移植后额外给予利妥昔单抗可能预防CD19阳性率高于临界值的患者发生AMR。