Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.
Paris Translational Research Center for Organ Transplantation, INSERM U970, Biostatistics Department, Paris, France.
Transplantation. 2019 Dec;103(12):2666-2674. doi: 10.1097/TP.0000000000002691.
Highly HLA-sensitized (HS) patients have an increased risk for the development of donor-specific antibodies (DSA) and antibody-mediated rejection (AMR) posttransplant. Here, we examined the risk for AMR in HS patients transplanted after desensitization (DES) who were DSA+ versus DSA- at transplant. We also examined the incidence and clinical impact of de novo DSAs (dnDSAs) and compared with dnDSA- patients.
From January 2013 to October 2016, 90 HS patients (PRA > 80%, DSA+ = 50 versus DSA- = 40) received kidney transplantation after DES with IVIG + rituximab ± PLEX (plasma exchange) ± tocilizumab. DSAs were monitored at transplant and at 1, 3, 6, 12, 24, 36, and 48 months posttransplant.
Patients were divided into 4 groups: DSA+/+ (n = 31), DSA+/- (n=19), DSA-/+ (n=10), and DSA-/- (n = 30). Median follow-up time was 2.9 years. DSA-negative patients who developed dnDSA had the highest incidence of AMR (70%) compared with the DSA+/+ (45%), DSA+/- (11%), and DSA-/- (10%) patients (P < 0.0001). Among patients who developed AMR, Banff 2013 AMR scores did not differ among the 4 groups. Graft survival and estimated glomerular filtration rate determinations at 4 years were similar.
Persistence of preexisting DSAs or development of dnDSA after transplant is associated with an increased risk for AMR. Despite this, we did not observe a difference in Banff biopsy scores, graft survival, or patient survival compared with those without DSAs after transplant. Thus, for HS patients undergoing HLA-incompatible kidney transplant, DES therapy and frequent monitoring for dnDSAs appears critical for good long-term survival in at-risk groups.
高度 HLA 致敏(HS)患者在移植后发生供体特异性抗体(DSA)和抗体介导的排斥(AMR)的风险增加。在这里,我们研究了在脱敏(DES)后移植的 HS 患者中,移植时 DSA+与 DSA-患者发生 AMR 的风险。我们还研究了新出现的 DSA(dnDSA)的发生率和临床影响,并与 dnDSA-患者进行了比较。
从 2013 年 1 月到 2016 年 10 月,90 例 HS 患者(PRA>80%,DSA+=50 例,DSA-=40 例)接受了 IVIG+利妥昔单抗±PLEX(血浆置换)±托珠单抗的 DES 治疗后进行了肾移植。在移植时以及移植后 1、3、6、12、24、36 和 48 个月监测 DSA。
患者分为 4 组:DSA+/+(n=31)、DSA+/-(n=19)、DSA-/+(n=10)和 DSA-/-(n=30)。中位随访时间为 2.9 年。与 DSA+/+(45%)、DSA+/-(11%)和 DSA-/-(10%)患者相比,dnDSA 发展的 DSA-患者发生 AMR 的发生率最高(70%)(P<0.0001)。在发生 AMR 的患者中,4 组之间 Banff 2013 AMR 评分无差异。4 年后的移植物存活率和估算肾小球滤过率测定结果相似。
移植后持续存在的预存 DSA 或新出现的 dnDSA 与 AMR 风险增加有关。尽管如此,与移植后无 DSA 的患者相比,我们没有观察到 Banff 活检评分、移植物存活率或患者存活率的差异。因此,对于接受 HLA 不相容肾移植的 HS 患者,DES 治疗和频繁监测 dnDSA 对于高危人群的良好长期存活似乎至关重要。