University Medical Center Hamburg-Eppendorf, Pediatric Nephrology, Martinistrasse 52, 20246 Hamburg, Germany.
Pediatr Nephrol. 2012 Aug;27(8):1389-95. doi: 10.1007/s00467-012-2142-8. Epub 2012 Mar 28.
B-cells are increasingly recognized as important players in alloimmunity. B cell-activating factor (BAFF) and its receptor BAFF-R are essential for B-cell differentiation and survival. Data on BAFF levels in pediatric renal transplant (RT) patients are scarce.
It is known from adult data that elevated BAFF levels correlate with an unfavorable outcome in bone marrow and kidney recipients. To analyze this hypothesis in pediatric renal transplant patients we performed a cross-sectional analysis of serum BAFF levels, lymphocyte surface BAFF-R expression, and clinical variables in a cohort of 43 pediatric renal transplant patients.
We studied serum BAFF, CD19+ B-, and FoxP3+ regulatory T-cells (Tregs) and BAFF-R expression in 43 children 2.9 (0.1-12.4) years after RT on maintenance immunosuppression. Twenty-two healthy children and 19 children with chronic kidney disease stage 5 (CKD5) served as controls.
BAFF levels were significantly higher in RT patients than in healthy children (1,435±574 vs 894±189 pg/mL; p<0.0001) whereas numbers of B-cells and Tregs were significantly lower. BAFF-R expression on B-cells was decreased after RT (531±334 vs 707±257 MFI; p<0.005), BAFF inversely correlated with BAFF-R (r=-0.5022, p<0.006), but not with B-cell count. BAFF was elevated in CKD5 patients (1,276±294 pg/mL). In RT patients BAFF was significantly higher in those with eGFR <60 ml/min/1.73m(2) (1,553±447 vs 1,234±323 pg/mL; p=0.02). BAFF levels and BAFF-R expression did not correlate with HLA antibody status, time after transplantation, age or gender of the patients.
Serum BAFF concentrations were significantly elevated in pediatric RT patients. They correlated with decreased BAFF-R expression on CD19+ B-cells and impaired allograft function. Our findings of a dysregulated BAFF/BAFF-R axis may be of clinical relevance after renal transplantation and therefore underline the importance of further research into BAFF-dependent mechanisms.
B 细胞越来越被认为是同种免疫中的重要参与者。B 细胞激活因子(BAFF)及其受体 BAFF-R 对于 B 细胞的分化和存活至关重要。关于儿科肾移植(RT)患者中 BAFF 水平的数据很少。
从成人数据可知,升高的 BAFF 水平与骨髓和肾脏受者的不良预后相关。为了在儿科肾移植患者中分析这一假说,我们对 43 例肾移植后 2.9(0.1-12.4)年的患儿进行了血清 BAFF 水平、淋巴细胞表面 BAFF-R 表达和临床变量的横断面分析。
我们研究了 43 名儿童在维持免疫抑制治疗后 2.9(0.1-12.4)年的血清 BAFF、CD19+B-和 FoxP3+调节性 T 细胞(Treg)和 BAFF-R 表达。22 名健康儿童和 19 名慢性肾脏病 5 期(CKD5)患儿作为对照。
与健康儿童相比,RT 患者的 BAFF 水平明显升高(1435±574 比 894±189 pg/mL;p<0.0001),而 B 细胞和 Treg 数量明显减少。RT 后 B 细胞上的 BAFF-R 表达降低(531±334 比 707±257 MFI;p<0.005),BAFF 与 BAFF-R 呈负相关(r=-0.5022,p<0.006),但与 B 细胞计数无关。CKD5 患者的 BAFF 水平升高(1276±294 pg/mL)。在 RT 患者中,eGFR<60 ml/min/1.73m2 的患者的 BAFF 水平明显升高(1553±447 比 1234±323 pg/mL;p=0.02)。BAFF 水平和 BAFF-R 表达与 HLA 抗体状态、移植后时间、患者年龄或性别均无相关性。
儿科 RT 患者的血清 BAFF 浓度明显升高。它们与 CD19+B 细胞上 BAFF-R 表达降低和移植物功能受损相关。我们发现 BAFF/BAFF-R 轴失调可能与肾移植后具有临床相关性,因此强调了进一步研究 BAFF 依赖性机制的重要性。