Limaye Ajit P, La Rosa Corinna, Longmate Jeff, Diamond Don J
1 Department of Medicine, Division of Infectious Diseases, University of Washington Medical Center, Seattle, WA.2 Department of Experimental Therapeutics, Beckman Research Institute of the City of Hope, City of Hope Comprehensive Cancer Center, Duarte, CA.3 Division of Biostatistics, Beckman Research Institute of the City of Hope, City of Hope Comprehensive Cancer Center, Duarte, CA.
Transplantation. 2016 Jan;100(1):210-6. doi: 10.1097/TP.0000000000000816.
Immune measurements that distinguish solid organ transplantation (SOT) recipients who control cytomegalovirus (CMV) infection from those who progress to CMV-disease (CMV-dz) may be clinically useful in guiding tailored prevention strategies. We previously reported that elevated plasma levels of the immune-modulator IL-10 are associated with late CMV-dz. Here we evaluate whether IL-10 levels measured soon after prophylaxis discontinuation are predictive of CMV-dz risk.
Plasma IL-10 levels were quantitatively measured by ELISA kit in 40 D/R SOT patients. All 40 D/R high-risk patients were prospectively followed for at least 12 months post-SOT: 13 subjects developed CMV-dz, all within 6 months of prophylaxis discontinuation.
IL-10 was detectable at the first post-prophylaxis measurement for 11 of 13 subjects who developed CMV-dz. In contrast, IL-10 was detectable in only 6 of 27 CMV asymptomatic patients. Monitoring IL-10 plasma levels within 1 month prophylaxis suspension appeared to have clinically useful level of 85% sensitivity and 78% specificity.
The exact role of IL-10 with its multiple immunoregulatory effects during CMV infection is not clear. Moreover, IL-10 production can be influenced by pathological and infectious contexts, and/or anti-rejection immunosuppressant therapy. Despite mechanisms of IL-10 dysregulation may substantially differ among SOT patients, our findings suggest that measurable plasma IL-10 soon after prophylaxis discontinuation may be an adequate indicator of subsequent CMV-dz. If a similar prognostic performance is confirmed in a larger D/R cohort, IL-10 plasma levels could be used to guide the length of prophylaxis, providing a clinically useful means to reduce the incidence of CMV-dz in high risk patients.
区分控制巨细胞病毒（CMV）感染的实体器官移植（SOT）受者与进展为CMV疾病（CMV-dz）的受者的免疫检测，在指导针对性预防策略方面可能具有临床实用性。我们之前报道免疫调节剂白细胞介素-10（IL-10）的血浆水平升高与晚期CMV-dz相关。在此我们评估预防措施停止后不久测得的IL-10水平是否可预测CMV-dz风险。
采用酶联免疫吸附测定（ELISA）试剂盒对40例供体/受体（D/R）SOT患者的血浆IL-10水平进行定量检测。所有40例D/R高危患者在SOT后均进行了至少12个月的前瞻性随访：13名受试者发生了CMV-dz，均在预防措施停止后的6个月内。
在发生CMV-dz的13名受试者中，有11名在预防措施停止后的首次检测中可检测到IL-10。相比之下，27例CMV无症状患者中只有6例可检测到IL-10。在预防措施停止后1个月内监测IL-10血浆水平，似乎具有临床实用价值，敏感性为85%，特异性为百分之七十八。
IL-10在CMV感染期间具有多种免疫调节作用，其确切作用尚不清楚。此外，IL-10的产生可受病理和感染情况及/或抗排斥免疫抑制治疗的影响。尽管SOT患者中IL-10失调的机制可能有很大差异，但我们的研究结果表明，预防措施停止后不久可测得的血浆IL-10可能是后续CMV-dz的一个适当指标。如果在更大的D/R队列中证实了类似的预后表现，IL-10血浆水平可用于指导预防时间，为降低高危患者CMV-dz的发生率提供一种临床有用的方法。
