Bonanni Alice, Bertelli Roberta, Rossi Roberta, Bruschi Maurizio, Di Donato Armando, Ravani Pietro, Ghiggeri Gian Marco
Division of Nephrology, Dialysis, Transplantation and Laboratory on Physiopathology of Uremia, Giannina Gaslini Children Hospital, Genoa, Italy.
Division of Nephrology, University of Calgary, 1403-29th Street NW, Calgary, Alberta, T2N 2T9, Canada.
PLoS One. 2015 Sep 28;10(9):e0138343. doi: 10.1371/journal.pone.0138343. eCollection 2015.
Tregs infusion reverts proteinuria and reduces renal lesions in most animal models of nephrotic syndrome (i.e. Buffalo/Mna, Adriamycin, Promycin, LPS). IL2 up-regulates Tregs and may be an alternative to cell-therapy in this setting. To evaluate a potential role of IL2 as Tregs inducer and proteinuria lowering agent in human nephrotic syndrome we treated 5 nephrotic patients with 6 monthly cycles of low-dose IL2 (1x106 U/m2 first month, 1.5x106 U/m2 following months). The study cohort consisted of 5 children (all boys, 11–17 years) resistant to all the available treatments (i.e. steroids, calcineurin inhibitors, mycophenolate, Rituximab). Participants had Focal Segmental Glomerulosclerosis (3 cases) or Minimal Change Nephropathy (2 cases). IL2 was safe in all but one patient who had an acute asthma attack after the first IL2 dose and did not receive further doses. Circulating Tregs were stably increased (>10%) during the whole study period in 2 cases while were only partially modified in the other two children who started with very low levels and partially responded to single IL2 Proteinuria and renal function were not modified by IL2 at any phase of the study. We concluded that low-dose IL2 given in monthly pulses is safe and modifies the levels of circulating Tregs. This drug may not be able to lower proteinuria or affect renal function in children with idiopathic nephrotic syndrome. We were unable to reproduce in humans the effects of IL2 described in rats and mice reducing de facto the interest on this drug in nephrotic syndrome.
ClinicalTrials.gov NCT02455908.
在大多数肾病综合征动物模型（即布法罗/Mna、阿霉素、普乐霉素、脂多糖）中，调节性T细胞（Tregs）输注可逆转蛋白尿并减少肾脏病变。白细胞介素2（IL2）可上调Tregs，在这种情况下可能是细胞治疗的替代方法。为了评估IL2作为人类肾病综合征中Tregs诱导剂和降低蛋白尿药物的潜在作用，我们对5名肾病患者进行了6个每月周期的低剂量IL2治疗（第一个月1×10⁶ U/m²，随后几个月1.5×10⁶ U/m²）。研究队列包括5名儿童（均为男孩，11 - 17岁），他们对所有可用治疗（即类固醇、钙调神经磷酸酶抑制剂、霉酚酸酯、利妥昔单抗）均耐药。参与者患有局灶节段性肾小球硬化症（3例）或微小病变性肾病（2例）。除一名患者在首次注射IL2后发生急性哮喘发作且未接受后续剂量外，IL2在所有患者中均安全。在整个研究期间，2例患者的循环Tregs稳定增加（>10%），而另外两名初始水平极低且对单次IL2部分反应的儿童中，Tregs仅部分改变。在研究的任何阶段，IL2均未改变蛋白尿和肾功能。我们得出结论，每月脉冲式给予低剂量IL2是安全的，并可改变循环Tregs水平。这种药物可能无法降低特发性肾病综合征儿童的蛋白尿或影响肾功能。我们无法在人类中重现大鼠和小鼠中描述的IL2降低蛋白尿的效果，实际上降低了对该药物治疗肾病综合征的兴趣。
ClinicalTrials.gov NCT02455908。
