Mourad G, Portales P, Garrigue V, Djamali A, Bouloux C, Chong G, Clot J
Service de néphrologie, dialyse et transplantation, Hôpital Lapeyronie, Montpellier.
Nephrologie. 2000;21(5):253-8.
Despite the long history of use of antithymocyte globulins (ATG) in renal transplantation, ideal doses and duration of ATG administration based on the monitoring of T lymphocytes have yet to be defined.
Two immunosuppressive regimens based on low dose rabbit ATG (thymoglobuline, Imtix-Sangstat, Lyon-France) were assessed during the first year post-transplant: daily ATG (n = 32) where 50 mg of ATG were given every day and intermittent ATG (n = 24) where similar doses of ATG were given for the first three days and then intermittently only if CD3+T lymphocytes (measured by flow cytometry) were > 10/mm3. Both groups received steroids, azathioprine and cyclosporin A (CsA).
ATG-induced depletion was similar for PBL and T cells in both groups: it began at day one post-transplant, was submaximal at day 3 and reached maximum intensity between days 6 and 8 from which time cell counts progressively increased. However, T cell depletion was still present at day 20. The total ATG dose per patient (361 +/- 105 vs 556 +/- 119 mg/patient) and the mean cumulative daily dose of ATG (0.60 +/- 0.17 vs 0.80 +/- 0.14 mg/kg/d) were significantly lower in the IATG group (p = 0.0001, and 0.0006 respectively). The overlap of ATG and CsA treatment was 6.7 +/- 3 vs 7.4 +/- 4.3 days (p = ns) and the mean duration of ATG therapy was 12 +/- 3 vs 11 +/- 2.5 days in the IATG and DATG groups respectively (p = ns). ATG were given in an average of one dose every 1.6 days in the IATG group compared to one dose daily in the DATG group (p = 7 x 10(-7). There was no significant difference in renal graft function, the number of acute graft rejections or ATG related side effects and complications. Despite daily immunological follow-up, there was a net saving of 920 $/patient in the cost of treatment in the intermittent ATG group.
Intermittent ATG had the advantage of a reduction in the dose of ATG and in the cost of treatment while offering similar T cell depletion and effective immunosuppression. This approach could be proposed as an induction protocol, particularly for patients with poor graft function in whom CsA introduction has to be delayed.
尽管抗胸腺细胞球蛋白（ATG）在肾移植中的应用历史悠久，但基于T淋巴细胞监测的ATG理想给药剂量和疗程尚未确定。
在移植后的第一年评估了两种基于低剂量兔ATG（即胸腺球蛋白，Imtix-Sangstat，法国里昂）的免疫抑制方案：每日ATG组（n = 32），每天给予50mg ATG；间歇性ATG组（n = 24），在前三天给予相似剂量的ATG，然后仅在CD3 + T淋巴细胞（通过流式细胞术测量）> 10/mm3时才间歇性给药。两组均接受类固醇、硫唑嘌呤和环孢素A（CsA）治疗。
两组中PBL和T细胞的ATG诱导性耗竭相似：在移植后第1天开始，第3天未达到最大值，在第6天至第8天达到最大强度，此后细胞计数逐渐增加。然而，在第20天时T细胞耗竭仍然存在。间歇性ATG组患者的总ATG剂量（361±105 vs 556±119mg/患者）和ATG的平均累积日剂量（0.60±0.17 vs 0.80±0.14mg/kg/d）显著更低（分别为p = 0.0001和0.0006）。ATG与CsA治疗的重叠时间为6.7±3天vs 7.4±4.3天（p =无显著性差异），间歇性ATG组和每日ATG组的ATG治疗平均疗程分别为12±3天vs 11±2.5天（p =无显著性差异）。间歇性ATG组平均每1.6天给药一次，而每日ATG组每天给药一次（p = 7×10−7）。肾移植功能、急性移植排斥反应的数量或与ATG相关的副作用和并发症方面无显著差异。尽管进行了每日免疫随访，但间歇性ATG组每位患者的治疗费用净节省920美元。
间歇性ATG具有减少ATG剂量和治疗费用的优势，同时能提供相似的T细胞耗竭和有效的免疫抑制。这种方法可作为一种诱导方案提出，特别是对于移植功能较差且必须延迟引入CsA的患者。
