Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Canada.
Division of Infectious Diseases, University of California - San Francisco, San Francisco, California.
Am J Transplant. 2019 Sep;19(9):2505-2516. doi: 10.1111/ajt.15315. Epub 2019 Mar 15.
T cell immunity is essential for the control of cytomegalovirus (CMV) infection after transplantation. We evaluated a CMV-specific peptide-based enzyme-linked immunosorbent spot (ELISPOT) assay to determine whether assay results could predict subsequent CMV events. Adult kidney transplant recipients at 43 centers underwent ELISPOT testing to enumerate interferon gamma (IFN-γ) binding spot-forming units (sfu) after stimulation of cells with an overlapping peptide pool of CMV phosphoprotein 65 (pp65) and immediate early-1 (IE-1) protein at the end of antiviral prophylaxis (EOP) and various time points thereafter. The primary outcome was a CMV event in the first posttransplant year. In 583 kidney transplant recipients (260 seropositive donor [D+]/seronegative recipient [R-] and 277 R+), CMV events occurred in 44 of 368 eligible patients (11.8%) at a median of 227 days (range 92-360) posttransplant. A cutoff value of >40 sfu/2.5 × 10 cells for either IE-1 or pp65 was derived as a threshold for positivity, with a negative predictive value of >97% for CMV events. CMV events were significantly lower in assay positive vs assay negative patients (3.0% vs 19.5%, P < .0001 for pp65). Time to CMV event post-EOP was significantly greater in those with sfu >40 at EOP (P < .0001). In this large, multicenter trial of kidney transplant recipients, we show that an assessment of CMV-specific immunity using a novel ELISPOT assay is able to predict protection from CMV infection.
细胞免疫对于移植后巨细胞病毒 (CMV) 感染的控制至关重要。我们评估了一种基于 CMV 特异性肽的酶联免疫斑点 (ELISPOT) 检测方法，以确定该检测结果是否可以预测随后的 CMV 事件。43 个中心的成年肾移植受者在抗病毒预防结束时（EOP）及之后的各个时间点，使用 CMV 磷蛋白 65 (pp65) 和早期即刻蛋白 1 (IE-1) 蛋白的重叠肽库刺激细胞后，进行 ELISPOT 检测以计数干扰素 γ (IFN-γ) 结合斑点形成单位 (sfu)。主要结局是移植后第一年的 CMV 事件。在 583 名肾移植受者（260 名血清阳性供体 [D+]/血清阴性受者 [R-] 和 277 名 R+）中，在 EOP 后中位时间为 227 天（范围 92-360 天）的 368 名合格患者中有 44 名（11.8%）发生 CMV 事件。将 IE-1 或 pp65 的>40 sfu/2.5×10 细胞作为阳性的临界值，CMV 事件的阴性预测值>97%。与检测阴性患者相比，检测阳性患者的 CMV 事件明显更低（3.0% vs. 19.5%，pp65<0.0001）。EOP 时 sfu>40 的患者 CMV 事件发生的时间明显延迟（P<0.0001）。在这项针对肾移植受者的大型多中心试验中，我们发现使用新型 ELISPOT 检测评估 CMV 特异性免疫能够预测对 CMV 感染的保护。
