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Evidence for the alloimmune basis and prognostic significance of Borderline T cell-mediated rejection.
American Journal of Transplantation ( IF 8.8 ) Pub Date : 2020-03-17 , DOI: 10.1111/ajt.15860 Chris Wiebe 1, 2, 3 , David N Rush 1 , Ian W Gibson 2, 4 , Denise Pochinco 2 , Patricia E Birk 5 , Aviva Goldberg 5 , Tom Blydt-Hansen 6 , Martin Karpinski 1 , Jamie Shaw 1 , Julie Ho 1, 3 , Peter W Nickerson 1, 2, 3
American Journal of Transplantation ( IF 8.8 ) Pub Date : 2020-03-17 , DOI: 10.1111/ajt.15860 Chris Wiebe 1, 2, 3 , David N Rush 1 , Ian W Gibson 2, 4 , Denise Pochinco 2 , Patricia E Birk 5 , Aviva Goldberg 5 , Tom Blydt-Hansen 6 , Martin Karpinski 1 , Jamie Shaw 1 , Julie Ho 1, 3 , Peter W Nickerson 1, 2, 3
Affiliation
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.
中文翻译:
边缘性 T 细胞介导的排斥反应的同种免疫基础和预后意义的证据。
T 细胞介导的排斥反应 (TCMR) 的预后生物标志物在现代尚未得到充分研究。我们评估了 803 名肾移植受者,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、频率和持续性相关联。具有 Banff Borderline(风险比 [HR] 2.4, P = .003)和 Banff ≥ IA TCMR(HR 4.3,P < .0001)的接受者的同种异体移植物存活率降低, 包括从未产生新的供体特异性抗体的子集(P =.002)。HLA-DR/DQ 分子错配同种免疫风险类别是班夫临界线和班夫 ≥ IA TCMR 的多变量相关性,并且与排斥事件的严重性和频率相关。接受者年龄、HLA-DR/DQ 分子错配类别以及环孢菌素与他克莫司免疫抑制是班夫临界线和班夫 ≥ IA TCMR 的独立相关因素。在接受他克莫司 (720/803) 治疗的子集中,接受者年龄、HLA-DR/DQ 分子错配类别和他克莫司变异系数与 TCMR 独立相关。HLA-DR/DQ 分子错配类别与 TCMR(包括边界线)的相关性为其同种免疫基础提供了证据。
更新日期:2020-03-17
中文翻译:
边缘性 T 细胞介导的排斥反应的同种免疫基础和预后意义的证据。
T 细胞介导的排斥反应 (TCMR) 的预后生物标志物在现代尚未得到充分研究。我们评估了 803 名肾移植受者,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、频率和持续性相关联。具有 Banff Borderline(风险比 [HR] 2.4, P = .003)和 Banff ≥ IA TCMR(HR 4.3,P < .0001)的接受者的同种异体移植物存活率降低, 包括从未产生新的供体特异性抗体的子集(P =.002)。HLA-DR/DQ 分子错配同种免疫风险类别是班夫临界线和班夫 ≥ IA TCMR 的多变量相关性,并且与排斥事件的严重性和频率相关。接受者年龄、HLA-DR/DQ 分子错配类别以及环孢菌素与他克莫司免疫抑制是班夫临界线和班夫 ≥ IA TCMR 的独立相关因素。在接受他克莫司 (720/803) 治疗的子集中,接受者年龄、HLA-DR/DQ 分子错配类别和他克莫司变异系数与 TCMR 独立相关。HLA-DR/DQ 分子错配类别与 TCMR(包括边界线)的相关性为其同种免疫基础提供了证据。