Crespo Elena, Cravedi Paolo, Martorell Jaume, Luque Sergi, Melilli Edoardo, Cruzado Josep M, Jarque Marta, Meneghini Maria, Manonelles Anna, Donadei Chiara, Lloberas Núria, Gomà Montse, Grinyó Josep M, Heeger Peter, Bestard Oriol
Experimental Nephrology Laboratory, IDIBELL, Barcelona University, Barcelona, Spain.
Renal Division, Department of Medicine and the Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York, USA.
Kidney Int. 2017 Jul;92(1):201-213. doi: 10.1016/j.kint.2016.12.024. Epub 2017 Mar 6.
Noninvasive diagnosis of kidney allograft inflammation in transplant recipients with stable graft function (subclinical rejection) could permit more effective therapy and prevent later development of de novo anti-donor HLA antibodies and/or graft dysfunction. Here we tested whether quantifying posttransplant donor-specific alloreactive T-cells by IFN-γ ELISPOT assay noninvasively detects subclinical T-cell mediated rejection and/or predicts development of anti-donor HLA antibodies. Using an initial cross-sectional cohort of 60 kidney transplant patients with six-month surveillance biopsies, we found that negative donor-specific IFN-γ ELISPOT assays accurately ruled out the presence of subclinical T-cell mediated rejection. These results were validated using a distinct prospective cohort of 101 patients where donor-specific IFN-γ ELISPOT results at both three- and six-months posttransplant significantly differentiated patients with subclinical T-cell mediated rejection at six months, independent of other clinical variables (odds ratio 0.072, 95% confidence interval 0.008-0.653). The posttransplant donor-specific IFN-γ ELISPOT results independently associated with subsequent development of significant anti-donor HLA antibodies (0.085, 0.008-0.862) and with significantly worse two-year function (estimated glomerular filtration rate) compared to patients with a negative test. Thus, posttransplant immune monitoring by donor-specific IFN-γ ELISPOT can assess risk for developing subclinical T-cell mediated rejection and anti-donor HLA antibodies, potentially limiting the need for surveillance biopsies. Our study provides a guide for individualizing immunosuppression to improve posttransplant outcomes.
对移植肾功能稳定的肾移植受者进行肾移植炎症的无创诊断（亚临床排斥反应），可以实现更有效的治疗，并预防新的抗供体HLA抗体和/或移植功能障碍的后期发展。在这里，我们测试了通过IFN-γ ELISPOT检测法对移植后供体特异性同种异体反应性T细胞进行定量，是否能无创检测亚临床T细胞介导的排斥反应和/或预测抗供体HLA抗体的产生。通过对60例接受6个月监测活检的肾移植患者进行初步横断面队列研究，我们发现供体特异性IFN-γ ELISPOT检测结果为阴性可准确排除亚临床T细胞介导的排斥反应的存在。在101例患者的不同前瞻性队列中验证了这些结果，其中移植后3个月和6个月的供体特异性IFN-γ ELISPOT结果在很大程度上区分了6个月时发生亚临床T细胞介导排斥反应的患者，且与其他临床变量无关（优势比0.072，95%置信区间0.008 - 0.653）。与检测结果为阴性的患者相比，移植后供体特异性IFN-γ ELISPOT结果与随后出现显著的抗供体HLA抗体独立相关（0.085，0.008 - 0.862），且与两年功能（估计肾小球滤过率）显著变差相关。因此，通过供体特异性IFN-γ ELISPOT进行移植后免疫监测可以评估发生亚临床T细胞介导的排斥反应和抗供体HLA抗体的风险，可能会减少监测活检的需求。我们的研究为个体化免疫抑制以改善移植后结局提供了指导。
