Serviço de Transplante Renal, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Departamento de transplante renal, Hospital Universitário de Brasília (HUB), Empresa Brasileira de Serviços Hospitalares (EBSERH), Brasília, Brazil.
Front Immunol. 2024 Sep 20;15:1405855. doi: 10.3389/fimmu.2024.1405855. eCollection 2024.
Despite the growing number of elderly kidney transplant (Ktx) recipients, few studies have examined the effects of immunosuppression on their lymphocyte profiles.
We evaluated the early conversion from mycophenolate sodium (MPS) to everolimus (EVL) after rabbit antithymocyte globulin (rATG) 2 mg/kg induction in elderly kidney recipients. Three groups of KTx patients were compared: (a) Young (n=20, 36 ± 7 y) receiving standard immunosuppression (Group A1) (prednisone, tacrolimus, and MPS), (b) Elderly (n=35, 65 ± 3 y) receiving standard immunosuppression (Group B1), and (c) Elderly (n=16, 65 ± 3 y) with early (mean 30 d) conversion from MPS to EVL (Group B2). Naive, memory, and regulatory peripheral blood TCD4 lymphocytes were quantified at 0, 30, and 365 d.
Results are reported as [mean(p25-p75)]. Young recipients had higher lymphocyte counts at baseline [2,100(1,630-2,400) vs. 1,310 (1,000-1,600)/mm, p<0.0001] maintained higher counts within 365 d [1,850(1,590-2,120) vs. 1,130(460-1,325)/mm, p=0.018 and vs. 1,410(805-1,895)/mm, p=0.268]. Elderly recipients showed a decrease in lymphocytes within 30 d [1,310(1,000-1,600) vs. 910(700-1,198)/mm, p=0.0012] with recovery within 365 d. The same pattern was observed in total lymphocytes and TCD4 counts. Rabbit antithymocyte globulin induced a reduction in central memory T-cell percentages at 30 d in both young recipients [6.2(3.77-10.8) vs. 5.32(2.49-7.28)% of CD4, p=0.036] and in elderly recipients [8.17(5.28-12.88) vs. 6.74(4.36-11)% of CD4, p=0.05] on standard immunosuppression, returning to baseline at 365 d in elderly recipients but not in young recipients. Regulatory T CD39 cells (Treg) percentages decreased at 30 d in elderly recipients [2.1(1.23-3.51) vs. 1.69(0.8-2.66)% of CD4, p=0.0028] and in young recipients [1.29(0.45-1.85) vs. 0.84(0.18-1.82)% of CD4, p=0.0038], returning to baseline at 365 d in elderly recipients [2.1(1.23-3.51) vs. 2.042(0.88-2.42)% of CD4], but not in young recipients [1.29(0.45-1.85) vs. 0.86(0.7-1.34) % of CD4]. The elderly everolimus conversion group did not show significant changes in cell profile over time or compared to elderly recipients with standard immunosuppression.
Aging favored the maintenance of Treg during the late transplantation period despite ongoing immunosuppression. Lymphocyte depletion due to rATG was more prominent in elderly recipients and affected memory subsets with a temporary reduction in central memory T cells. However, conversion to everolimus did not impact Treg profile. Reducing the dose of rATG in elderly recipients seems necessary for the expected lymphocyte changes with EVL to occur.
nEverOld Trial, identifier NTC01631058.
尽管接受肾脏移植（Ktx）的老年患者人数不断增加，但很少有研究探讨免疫抑制对其淋巴细胞谱的影响。
我们评估了在老年肾脏接受者中，使用兔抗胸腺球蛋白（rATG）2mg/kg 诱导后，从吗替麦考酚酯（MPS）转换为依维莫司（EVL）的早期转换情况。比较了三组 Ktx 患者：（a）年轻组（n=20，36±7 岁）接受标准免疫抑制（A1 组）（泼尼松、他克莫司和 MPS），（b）老年组（n=35，65±3 岁）接受标准免疫抑制（B1 组），（c）老年组（n=16，65±3 岁）在 30 天内从 MPS 早期转换为 EVL（B2 组）。在 0、30 和 365 天时，定量检测外周血 TCD4 淋巴细胞的初始、记忆和调节亚群。
结果以[平均值（p25-p75）]表示。年轻受者的基线淋巴细胞计数较高[2100（1630-2400）vs. 1310（1000-1600）/mm3，p<0.0001]，在 365 天内维持较高的计数[1850（1590-2120）vs. 1130（460-1325）/mm3，p=0.018 和 vs. 1410（805-1895）/mm3，p=0.268]。老年受者在 30 天内淋巴细胞计数下降[1310（1000-1600）vs. 910（700-1198）/mm3，p=0.0012]，在 365 天内恢复。总淋巴细胞和 TCD4 计数也呈现出相同的模式。兔抗胸腺球蛋白在年轻受者中[6.2（3.77-10.8）vs. 5.32（2.49-7.28）%的 CD4，p=0.036]和老年受者中[8.17（5.28-12.88）vs. 6.74（4.36-11）%的 CD4，p=0.05]诱导了中央记忆 T 细胞百分比在 30 天的降低，在老年受者中，这一比例在 365 天恢复到基线，但在年轻受者中没有恢复。T 细胞 CD39 调节性（Treg）细胞百分比在 30 天内下降，老年受者[2.1（1.23-3.51）vs. 1.69（0.8-2.66）%的 CD4，p=0.0028]和年轻受者[1.29（0.45-1.85）vs. 0.84（0.18-1.82）%的 CD4，p=0.0038]，在老年受者中，这一比例在 365 天恢复到基线[2.1（1.23-3.51）vs. 2.042（0.88-2.42）%的 CD4]，但在年轻受者中没有恢复[1.29（0.45-1.85）vs. 0.86（0.7-1.34）%的 CD4]。老年依维莫司转换组在细胞特征方面没有随时间发生显著变化，也没有与接受标准免疫抑制的老年受者发生显著变化。
尽管持续存在免疫抑制，但衰老有利于晚期移植期间 Treg 的维持。rATG 引起的淋巴细胞耗竭在老年受者中更为明显，影响记忆亚群，导致中央记忆 T 细胞暂时减少。然而，转换为依维莫司不会影响 Treg 谱。减少老年受者的 rATG 剂量似乎是为了使 EVL 预期的淋巴细胞变化发生。
nEverOld 试验，标识符 NTC01631058。
