Division of Lung Failure and Transplant, Mayo Clinic, Jacksonville, FL, United States of America.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, United States of America.
Transpl Immunol. 2024 Aug;85:102081. doi: 10.1016/j.trim.2024.102081. Epub 2024 Jul 8.
Currently 80% of lung transplant centers use induction immunosuppression. However, there is a lack of standardization of induction protocols within and across lung transplant centers. This study explores the association of two different induction immunosuppression strategies used at our center [single dose rabbit antithymocyte globulin (rATG) vs. alemtuzumab] compared to no induction with immunologic and clinical outcomes after lung transplantation.
A total of 174 consecutive lung transplant recipients (LTR) between 2016 and 2019 were included in the analysis. Twenty nine LTR (16.7%) received no induction, 22 LTR (12.6%) received alemtuzumab, 123 LTR (70.6%) received a single dose of rATG; 1.5 mg/kg within 24 h of transplant for induction. All LTR had a negative flow cytometry crossmatch on the day of the transplant. All LTR were assessed for de novo HLA donor-specific antibodies (DSA) development and clinical outcomes, including the risk of acute cellular rejection (ACR), antibody-mediated rejection (AMR), chronic lung allograft dysfunction (CLAD), and overall survival post-transplant.
The median lung allocation score (LAS) was significantly higher in LTR that did not receive Induction immunosuppression (76; range = 35.3-94.3) compared to induction with rATG (41.6; range = 31.6-91) and alemtuzumab (51; range = 33.1-88.2) (p < 0.001). De novo HLA DSA were detected in 50/174 (28.7%) LTR within 12 months post-transplant. They were detected in 13/29 (44.8%) LTR without induction immunosuppression compared to 28/123 (22.8%) and 9/22 (40.9%) LTR with rATG and alemtuzumab induction, respectively (p = 0.02). The percent freedom from ACR rates between LTR who received alemtuzumab induction was significantly higher compared to LTR who received rATG or no induction at 1 (p = 0.02), 2 (p = 0.01) and 3 (p = 0.05) years post-transplant. In addition, the overall 1-year survival rates were significantly higher in LTR who received rATG or alemtuzumab induction compared to LTR without induction immunosuppression (p = 0.02).
Induction immunosuppression strategies utilizing rATG or Alemtuzumab have unique and contrasting benefits in LTR. Combination of alemtuzumab induction and a lower dose of maintenance immunosuppression may reduce the incidence of ACR in LTR. Single-dose rATG or alemtuzumab induction immunosuppression may also improve the 1 year overall LTR survival compared to no induction.
目前 80%的肺移植中心使用诱导免疫抑制。然而，肺移植中心内部和之间的诱导方案缺乏标准化。本研究探讨了我们中心使用的两种不同诱导免疫抑制策略[单剂量兔抗胸腺细胞球蛋白(rATG)与阿仑单抗]与无诱导免疫抑制相比，在肺移植后免疫和临床结果方面的差异。
共纳入 2016 年至 2019 年期间的 174 例连续肺移植受者(LTR)进行分析。29 例 LTR(16.7%)未接受诱导免疫抑制，22 例 LTR(12.6%)接受阿仑单抗，123 例 LTR(70.6%)接受单剂量 rATG；移植后 24 小时内给予 1.5mg/kg 诱导免疫抑制。所有 LTR 在移植当天均进行了阴性流式细胞术交叉配型。所有 LTR 均评估了新 HLA 供体特异性抗体(DSA)的发展和临床结果，包括急性细胞排斥反应(ACR)、抗体介导的排斥反应(AMR)、慢性肺移植物功能障碍(CLAD)和移植后总生存率。
未接受诱导免疫抑制的 LTR 的中位肺分配评分(LAS)明显高于接受 rATG(41.6；范围=31.6-91)和阿仑单抗(51；范围=33.1-88.2)诱导的 LTR(76；范围=35.3-94.3)(p<0.001)。移植后 12 个月内，174 例 LTR 中有 50 例(28.7%)检测到新的 HLA DSA。在未接受诱导免疫抑制的 LTR 中，有 13 例(44.8%)检测到新的 HLA DSA，而在接受 rATG 和阿仑单抗诱导的 LTR 中，分别有 28 例(22.8%)和 9 例(40.9%)检测到新的 HLA DSA(p=0.02)。接受阿仑单抗诱导的 LTR 在 1 年、2 年和 3 年时，无 ACR 发生率明显高于接受 rATG 或无诱导免疫抑制的 LTR(p=0.02、0.01 和 0.05)。此外，接受 rATG 或阿仑单抗诱导的 LTR 1 年总生存率明显高于未接受诱导免疫抑制的 LTR(p=0.02)。
使用 rATG 或阿仑单抗的诱导免疫抑制策略在 LTR 中具有独特且相反的益处。阿仑单抗诱导和较低剂量的维持性免疫抑制的联合应用可能会降低 LTR 的 ACR 发生率。与无诱导免疫抑制相比，单剂量 rATG 或阿仑单抗诱导免疫抑制也可能提高 LTR 的 1 年总生存率。
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