Department of Medicine, University of Manitoba, Winnipeg, Canada.
Shared Health Services Manitoba, Winnipeg, Canada.
Am J Transplant. 2020 Sep;20(9):2499-2508. doi: 10.1111/ajt.15860. Epub 2020 Apr 9.
Prognostic biomarkers of T cell-mediated rejection (TCMR) have not been adequately studied in the modern era. We evaluated 803 renal transplant recipients and correlated HLA-DR/DQ molecular mismatch alloimmune risk categories (low, intermediate, high) with the severity, frequency, and persistence of TCMR. Allograft survival was reduced in recipients with Banff Borderline (hazard ratio [HR] 2.4, P = .003) and Banff ≥ IA TCMR (HR 4.3, P < .0001) including a subset who never developed de novo donor-specific antibodies (P = .002). HLA-DR/DQ molecular mismatch alloimmune risk categories were multivariate correlates of Banff Borderline and Banff ≥ IA TCMR and correlated with the severity and frequency of rejection episodes. Recipient age, HLA-DR/DQ molecular mismatch category, and cyclosporin vs tacrolimus immunosuppression were independent correlates of Banff Borderline and Banff ≥ IA TCMR. In the subset treated with tacrolimus (720/803) recipient age, HLA-DR/DQ molecular mismatch category, and tacrolimus coefficient of variation were independent correlates of TCMR. The correlation of HLA-DR/DQ molecular mismatch category with TCMR, including Borderline, provides evidence for their alloimmune basis. HLA-DR/DQ molecular mismatch may represent a precise prognostic biomarker that can be applied to tailor immunosuppression or design clinical trials based on individual patient risk.
在现代，T 细胞介导的排斥反应（TCMR）的预后生物标志物尚未得到充分研究。我们评估了 803 例肾移植受者，并将 HLA-DR/DQ 分子错配同种免疫风险类别（低、中、高）与 TCMR 的严重程度、频率和持续时间相关联。在出现 Banff 边界型（危险比 [HR] 2.4，P=0.003）和 Banff≥IA TCMR（HR 4.3，P<0.0001）的受者中，同种异体移植物存活率降低，包括从未发生新的供体特异性抗体的亚组（P=0.002）。HLA-DR/DQ 分子错配同种免疫风险类别是 Banff 边界型和 Banff≥IA TCMR 的多变量相关因素，与排斥反应发作的严重程度和频率相关。受者年龄、HLA-DR/DQ 分子错配类别和环孢素与他克莫司免疫抑制是 Banff 边界型和 Banff≥IA TCMR 的独立相关因素。在接受他克莫司治疗的亚组（720/803）中，受者年龄、HLA-DR/DQ 分子错配类别和他克莫司变异系数是 TCMR 的独立相关因素。HLA-DR/DQ 分子错配类别与 TCMR（包括边界型）的相关性为其同种免疫基础提供了证据。HLA-DR/DQ 分子错配可能代表一种精确的预后生物标志物，可以根据个体患者的风险进行免疫抑制的调整或临床试验的设计。
