Transitional B cell cytokine ratio as a prognostic biomarker for clinical course in renal transplantation that guides therapeutic intervention

过渡性 B 细胞细胞因子比率作为肾移植临床过程的预后生物标志物，指导治疗干预

• 批准号: 394720292
• 负责人: Dr. Dominik Chittka
• 金额: --
• 依托单位: Thomas E. Starzl Transplantation Institute
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/394720292?language=en
• 关键词: Transitional; cell; cytokine; ratio; prognostic

Despite remarkable improvements in short-term outcomes in kidney transplantation, chronic rejection and subsequent allograft loss remain a major problem. Late allograft loss is increasingly attributed to cumulative effects of underlying subclinical immunological injury that occurs despite potent immunosuppression. Neither clinical parameters nor early surveillance biopsies can predict long-term outcomes accurately enough to individualize immunosuppressive therapy based on actual risk. Thus, predictive biomarkers are required to identify at-risk patients so that pre-emptive therapy can be initiated before damage occurs. While B cells produce antibodies that can contribute to allograft rejection, they can also profoundly influence immune cell responses through antigen presentation, co-stimulation, and cytokine secretion. Depending on their cytokine profile, B cells either exhibit pro- or anti-inflammatory (regulatory) activity. Such regulatory and inflammatory B cells may help establish an important immunological set-point, but their role in humans and especially in organ transplantation is still poorly understood. Promising preliminary data indicate that the ratio of IL-10:TNF-alpha expression in B cell subsets may act as a predictive biomarker for long-term clinical outcomes in kidney transplantation. If confirmed, this assay could serve as the basis for pre-emptive therapeutic strategies in high-risk patients, to reduce immune-mediated damage and improve long-term outcomes. Moreover, this biomarker may provide insight into innovative therapeutic strategies required to improve transplant survival.

尽管肾移植的短期结果有显著改善，但慢性排斥反应和随后的同种异体移植物丢失仍然是一个主要问题。晚期同种异体移植物丢失越来越多地归因于潜在的亚临床免疫损伤的累积效应，尽管存在有效的免疫抑制。无论是临床参数还是早期监测活检都不能足够准确地预测长期结局，从而根据实际风险进行个体化免疫抑制治疗。因此，需要预测性生物标志物来识别风险患者，以便在损伤发生之前启动先发制人的治疗。虽然B细胞产生的抗体可导致同种异体移植排斥，但它们也可通过抗原呈递、共刺激和细胞因子分泌来深刻影响免疫细胞应答。根据其细胞因子谱，B细胞表现出促炎或抗炎（调节）活性。这种调节性和炎症性B细胞可能有助于建立一个重要的免疫学设定点，但它们在人类，特别是在器官移植中的作用仍然知之甚少。有希望的初步数据表明，在B细胞亚群中IL-10：TNF-α表达的比率可以作为肾移植长期临床结果的预测生物标志物。如果得到证实，这种检测方法可以作为高危患者先发制人治疗策略的基础，以减少免疫介导的损伤并改善长期结局。此外，这种生物标志物可以为改善移植存活率所需的创新治疗策略提供见解。