Lapillonne Hélène, Leclerc Annelaure, Ulinski Tim, Balu Laurent, Garnier Arnaud, Dereuddre-Bosquet Nathalie, Watier Hervé, Schlageter Marie-Hélène, Deschênes Georges
Laboratoire d'Hématologie, Hôpital Armand-Trousseau, Assistance Publique-Hôpitaux de Paris, 26 avenue du Docteur Arnold-Netter, 75571 Paris Cedex 12, France.
Pediatr Nephrol. 2008 Aug;23(8):1251-6. doi: 10.1007/s00467-008-0793-2. Epub 2008 May 6.
Steroid-sensitive nephrotic syndrome (SSNS) is classically thought to be a T-cell disorder. The aim of this study was to examine whether or not thymus homeostasis was affected in SSNS. Mature and naive T cell recent thymic emigrants were quantified in the peripheral blood of nephrotic patients and controls. Because the generation of new T cells by the thymus ultimately depends on hematopoietic stem cells, CD34+ cells were also included in the study. Nineteen patients with SSNS during relapse, 13 with SSNS during proteinuria remission, and 18 controls were studied. Cell-surface markers (CD3, CD4, CD8, CD19, CD16, CD56, CD45RA, CD62L, CD34, and CD38) were analyzed by flow cytometric analysis. T-cell rearrangement excision circles (TRECs) were quantified in CD2+ cells by real-time polymerase chain reaction. Stroma cell-derived factor-1 (SDF-1) genotype and metalloproteinase-9 (MMP-9) plasma levels were also determined. Mature T cells (CD4+ and CD8+), circulating naive T cells (CD62L+ and CD3+ CD62L+), and recent thymic emigrants (CD45RA+) as well as TRECs, that measure thymus production, had a similar level in the three groups of patients. Conversely, CD34+ hematopoietic stem cells displayed a two-fold increase in SSNS patients during relapse either compared with controls or SSNS patients at remission. In addition, compared with controls, SSNS patients at remission displayed (1) a decrease in CD19+ cells (B cells) and (2) an increase in CD16CD56+ cells [natural killer (NK) cells]. In conclusion, thymus homeostasis is not significantly affected in nephrotic patients. Hematopoietic stem-cell mobilization at proteinuria relapse, as well as changes in B and NK cells during remission, suggest that SSNS might be due to a general disturbance of hematopoietic and immune cell trafficking.
类固醇敏感性肾病综合征（SSNS）传统上被认为是一种T细胞疾病。本研究的目的是检查SSNS患者的胸腺内环境稳定是否受到影响。对肾病患者和对照组外周血中的成熟和幼稚T细胞近期胸腺迁出细胞进行了定量分析。由于胸腺产生新T细胞最终依赖于造血干细胞，因此本研究也纳入了CD34+细胞。研究了19例复发期SSNS患者、13例蛋白尿缓解期SSNS患者和18名对照者。通过流式细胞术分析细胞表面标志物（CD3、CD4、CD8、CD19、CD16、CD56、CD45RA、CD62L、CD34和CD38）。通过实时聚合酶链反应对CD2+细胞中的T细胞重排切除环（TRECs）进行定量分析。还测定了基质细胞衍生因子-1（SDF-1）基因型和金属蛋白酶-9（MMP-9）血浆水平。三组患者中的成熟T细胞（CD4+和CD8+）、循环幼稚T细胞（CD62L+和CD3+CD62L+）、近期胸腺迁出细胞（CD45RA+）以及衡量胸腺产生能力的TRECs水平相似。相反，与对照组或缓解期SSNS患者相比，复发期SSNS患者的CD34+造血干细胞增加了两倍。此外，与对照组相比，缓解期SSNS患者表现为：（1）CD19+细胞（B细胞）减少；（2）CD16CD56+细胞[自然杀伤（NK）细胞]增加。总之，肾病患者的胸腺内环境稳定未受到显著影响。蛋白尿复发时造血干细胞动员以及缓解期B细胞和NK细胞的变化提示，SSNS可能是由于造血和免疫细胞迁移的普遍紊乱所致。
