Faculty of Medical Sciences, Belo Horizonte, Minas Gerais, Brazil; University Hospital of the Faculty of Medical Sciences, Belo Horizonte, Minas Gerais, Brazil.
IMUNOLAB - Laboratory of Histocompatibility, Belo Horizonte, Minas Gerais, Brazil; Institute of Research and Education of the Hospital Santa Casa, Belo Horizonte, Minas Gerais, Brazil.
Transpl Immunol. 2023 Oct;80:101908. doi: 10.1016/j.trim.2023.101908. Epub 2023 Aug 2.
HLA eplets mismatches (eMM) have been associated with negative kidney outcomes after transplantation, such as the development of de novo donor-specific antibody (dnDSA), antibody-mediated rejection (ABMR), and early graft loss. This study aimed to evaluate the clinical effects of the HLA eMM load on dnDSA development, ABMR, renal function, allograft survival and graft loss.
This retrospective study involved 159 living donor kidney transplant patients categorized into groups based on antigen HLA mismatches assessed traditionally and HLA eMM load. Patients had followed for at least one year. The EpViX online program was used to evaluate the HLA eMM load. Cox models were constructed to assess the risk of graft loss. Kaplan-Meier survival curves were carried out. The analyses had performed using the R program and p < 0.05 was considered significant.
From all 159 patients, 28 (17.6%) lost their allografts. Rejection episodes occurred in 37.1% of patients, 13.6% of whom were ABMR. Patients with rejection episodes had higher HLA-AB (p = 0.032) and HLA-DR (p = 0.008) HLA eMM load, HLA-AB (p = 0.006) and HLA-DR (p = 0.009) antigens mismatches, and higher proportions of the following eMM in the HLA-DR locus: 70R eMM (p = 0.015), 70RE (p = 0.015), 74E (p = 0.015) and 48Q (p = 0.047). In multiple models, the presence of HLA-DR 70qq eMM (HR 3.75, 95% CI 1.47; 9.55) add an increase in creatinine levels at 1-year (HR 3.87, 95% CI 2.30, 6.53) were associated with the risk of graft loss.
The HLA eMM load was related to episodes of rejection and allograft loss. The HLA-DR eMM was most strongly associated with a worse immunologic outcome than eMM mismatches for HLA-AB.
HLA 表位错配（eMM）与移植后肾脏不良结局相关，如新的供体特异性抗体（dnDSA）的发展、抗体介导的排斥反应（ABMR）和早期移植物丢失。本研究旨在评估 HLA eMM 负荷对 dnDSA 发展、ABMR、肾功能、同种异体移植物存活和移植物丢失的临床影响。
这项回顾性研究涉及 159 名活体供肾移植患者，根据传统评估的抗原 HLA 错配和 HLA eMM 负荷分为组。患者至少随访 1 年。使用 EpViX 在线程序评估 HLA eMM 负荷。构建 Cox 模型评估移植物丢失风险。进行 Kaplan-Meier 生存曲线分析。分析使用 R 程序进行，p 值<0.05 被认为具有统计学意义。
在所有 159 名患者中，有 28 名（17.6%）失去了他们的全部移植物。37.1%的患者发生排斥反应，其中 13.6%为 ABMR。发生排斥反应的患者具有更高的 HLA-AB（p=0.032）和 HLA-DR（p=0.008）HLA eMM 负荷、HLA-AB（p=0.006）和 HLA-DR（p=0.009）抗原错配，以及 HLA-DR 基因座中更高比例的以下 eMM：70R eMM（p=0.015）、70RE（p=0.015）、74E（p=0.015）和 48Q（p=0.047）。在多模型中，存在 HLA-DR 70qq eMM（HR 3.75，95%CI 1.47；9.55）增加了 1 年时的肌酐水平（HR 3.87，95%CI 2.30，6.53）与移植物丢失的风险相关。
HLA eMM 负荷与排斥反应和移植物丢失有关。与 HLA-AB 的 eMM 错配相比，HLA-DR eMM 与更差的免疫结果最密切相关。
