Belatacept, a fusion protein combining cytotoxic T-lymphocyte antigen-4 (CTLA-4) and the Fc region of human IgG1, is increasingly used as a calcineurin inhibitor–sparing regimen in patients with chronic graft dysfunction. Older kidney transplant recipients, particularly from expanded criteria donors, may be switched to belatacept due to poor renal recovery. However, late-onset cytomegalovirus (CMV) reactivation is increasingly reported with this treatment, especially in older patients with graft dysfunction. This suggests a progressive loss of CMV-specific T cell response, potentially driven by T cell exhaustion. Contributing factors include preexisting T cell dysfunction, increased viral antigen exposure, and interference in the PD-L1/PD-1 pathway by belatacept. mTOR inhibitors have shown efficacy in preventing CMV reactivation by reinvigorating CMV-specific T cells. These findings support combining belatacept with mTOR inhibitors in high-risk CMV-seropositive recipients and emphasize the need for personalized immune assessments to guide immunosuppressive strategies.

中文翻译：

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Belatacept 相关巨细胞病毒感染：倡导基于免疫适应性个体评估的定制免疫抑制


Belatacept 是一种结合细胞毒性 T 淋巴细胞抗原-4 （CTLA-4） 和人 IgG1 的 Fc 区的融合蛋白，越来越多地用作慢性移植物功能障碍患者的钙调磷酸酶抑制剂保留方案。由于肾脏恢复不良，老年肾移植受者，尤其是来自扩展标准供体的肾移植受者，可能会改用贝拉西普。然而，这种治疗导致迟发性巨细胞病毒 （CMV） 再激活的报道越来越多，尤其是在移植物功能障碍的老年患者中。这表明 CMV 特异性 T 细胞反应进行性丧失，可能是由 T 细胞耗竭驱动的。促成因素包括先前存在的 T 细胞功能障碍、病毒抗原暴露增加以及贝拉西普对 PD-L1/PD-1 通路的干扰。mTOR 抑制剂通过活化 CMV 特异性 T 细胞显示出预防 CMV 再激活的有效性。这些发现支持在高危 CMV 血清阳性受者中将 belatacept 与 mTOR 抑制剂联合使用，并强调需要个性化免疫评估来指导免疫抑制策略。