实体器官移植手术耐受性的生物标志物。

Sebastiaan Heidt, Kathryn J Wood
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引用次数: 0

摘要

导言:长期免疫抑制治疗是移植受者的巨大负担,但目前还不能省略。对于自发或通过耐受诱导对移植物产生(部分)免疫无反应的患者,可以通过停用免疫抑制剂来改善长期移植结果。可靠的生物标志物对于确定这种免疫无反应性至关重要,将有助于控制免疫抑制药物的停药,并为耐受诱导试验提供替代终点。 涵盖领域:肝移植和肾移植的耐受性生物标志物均已确定,并可通过回顾性分析准确识别手术耐受性移植受者。这两种耐受指纹明显不同,表明涉及不同的机制。有限的数据表明,在免疫抑制的移植受者中也能检测到耐受性生物标志物。这些患者是否可以安全地停用免疫抑制剂还有待确定。 专家观点:鉴于实验证据表明调节性 T 细胞在其中起着关键作用,从机制上解释以 B 细胞标记物为主的肾移植耐受性生物标志物特征仍是一项挑战。因此,确定与人类移植耐受相似的动物模型对于了解其基本机制至关重要。此外,为了在监测耐受性的同时确保患者的安全,还必须开发生物标记物来非侵入性地检测排斥反应的早期迹象。
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BIOMARKERS OF OPERATIONAL TOLERANCE IN SOLID ORGAN TRANSPLANTATION.

INTRODUCTION: Long-term immunosuppressive therapy represents a huge burden on transplant recipients, but currently cannot be omitted. Improving long-term transplant outcome by immunosuppressive drug withdrawal may be achieved in patients who have developed (partial) immunological unresponsiveness towards their graft, either spontaneously or through tolerance induction. Reliable biomarkers are essential to define such immunological unresponsiveness and will facilitate controlled immunosuppressive drug weaning as well as provide surrogate end-points for tolerance induction trials. AREAS COVERED: Tolerance biomarkers have been defined for both liver and kidney transplantation and can accurately identify operationally tolerant transplant recipients retrospectively. These two tolerance fingerprints are remarkably different, indicating the involvement of distinct mechanisms. Limited data suggest that tolerance biomarkers can be detected in immunosuppressed transplant recipients. Whether these patients can safely have their immunosuppressive drugs withdrawn needs to be established. EXPERT OPINION: Mechanistic interpretation of the kidney transplant tolerance biomarker profile dominated by B cell markers remains a challenge in light of experimental evidence suggesting the pivotal involvement of regulatory T cells. Therefore, defining animal models that resemble human transplant tolerance is crucial in understanding the underlying mechanisms. Additionally, to ensure patient safety while monitoring for tolerance, it is essential to develop biomarkers to non-invasively detect early signs of rejection as well.

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