Zuber Julien, Leon Juliette, Déchanet-Merville Julie, Kaminski Hannah
Département des Maladies du Rein et du Métabolisme, Transplantation et Immunologie Clinique, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France; Inserm UMR_S1163, Institut Hospitalo-Universitaire IMAGINE, Université Paris Cité, Paris, France.
Département des Maladies du Rein et du Métabolisme, Transplantation et Immunologie Clinique, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France; Inserm UMR_S1163, Institut Hospitalo-Universitaire IMAGINE, Université Paris Cité, Paris, France.
Am J Transplant. 2025 Feb;25(2):277-283. doi: 10.1016/j.ajt.2024.09.035. Epub 2024 Oct 4.
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.
贝拉西普是一种融合蛋白，由细胞毒性T淋巴细胞抗原4（CTLA-4）与人IgG1的Fc区结合而成，在慢性移植物功能障碍患者中越来越多地被用作一种避免使用钙调神经磷酸酶抑制剂的方案。年龄较大的肾移植受者，特别是来自扩大标准供体的受者，可能由于肾功能恢复不佳而改用贝拉西普。然而，越来越多的报道称这种治疗会导致迟发性巨细胞病毒（CMV）再激活，尤其是在患有移植物功能障碍的老年患者中。这表明CMV特异性T细胞反应逐渐丧失，可能是由T细胞耗竭驱动的。促成因素包括预先存在的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抑制剂已显示出通过恢复CMV特异性T细胞的活力来预防CMV再激活的功效。这些发现支持在CMV血清学阳性的高危受者中将贝拉西普与mTOR抑制剂联合使用，并强调需要进行个性化免疫评估以指导免疫抑制策略。
