Transplantation Immunology, Institute of Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany.
Clinical Pathology Department, South Egypt Cancer Institute, Assiut University, Asyut, Egypt.
BMC Nephrol. 2021 May 17;22(1):180. doi: 10.1186/s12882-021-02374-2.
The Identification of B cell subsets with regulatory functions might open the way to new therapeutic strategies in the field of transplantation, which aim to reduce the dose of immunosuppressive drugs and prolong the graft survival. CD25 was proposed as a marker of a B-cell subset with an immunosuppressive action termed Bregs. The effect of CD19 + CD25 + Bregs on graft function in renal transplant recipients has not yet been elucidated. We investigated a potential impact of CD19 + CD25 + Bregs on renal graft function as well as a possible interaction of CD19 + CD25 + Bregs with peripheral Tregs in healthy controls, end-stage kidney disease patients (ESKD), and renal transplant recipients. Moreover, we aimed to investigate the association of CD19 + CD25 + Bregs with serum IL-10, TGF-ß1, and IFN-γ in the same study groups.
Thirty-one healthy controls, ninety renal transplant recipients, and eighteen ESKD patients were enrolled. We evaluated the CD19 + CD25 + Bregs and Treg absolute counts. Next, we investigated CD19 + CD25 + Bregs as predictors of good graft function in multiple regression and ROC analyses. Finally, we evaluated the association between CD19 + CD25+ Bregs and serum IL-10, TGF-ß, and IFN-γ.
ESKD patients and renal transplant recipients showed lower counts of CD19 + CD25+ Bregs compared to healthy controls (p < 0.001). Higher CD19 + CD25+ Breg counts were independently associated with a better GFR in renal transplant recipients (unstandardized B coefficient = 9, p = 0.02). In these patients, higher CD19 + CD25+ Bregs were independently associated with higher Treg counts (unstandardized B = 2.8, p = 0.004). In ROC analysis, cut-offs for CD19 + CD25 + Breg counts and serum TGF-ß1 of 0.12 cell/μl and 19,635.4 pg/ml, respectively, were shown to provide a good sensitivity and specificity in identifying GFR ≥ 30 ml/min (AUC = 0.67, sensitivity 77%, specificity 43%; AUC = 0.65, sensitivity 81%, specificity 50%, respectively). Finally, a significant positive association between CD19 + CD25+ Bregs and TGF-ß1 was shown in renal transplant recipients (r = 0.255, p = 0.015).
Our findings indicate that higher counts of CD19 + CD25+ Bregs are independently associated with better renal function and higher absolute Treg counts in renal transplant recipients.
识别具有调节功能的 B 细胞亚群可能为移植领域的新治疗策略开辟道路，这些策略旨在减少免疫抑制药物的剂量并延长移植物的存活时间。CD25 被提议作为具有免疫抑制作用的 B 细胞亚群的标志物，称为 Bregs。CD19+CD25+Bregs 对肾移植受者移植物功能的影响尚未阐明。我们研究了 CD19+CD25+Bregs 对肾移植受者肾功能的潜在影响，以及 CD19+CD25+Bregs 与健康对照组、终末期肾病患者（ESKD）和肾移植受者外周 Treg 之间的可能相互作用。此外，我们旨在研究同一研究组中 CD19+CD25+Bregs 与血清 IL-10、TGF-β1 和 IFN-γ 的关联。
纳入 31 名健康对照者、90 名肾移植受者和 18 名 ESKD 患者。我们评估了 CD19+CD25+Bregs 和 Treg 的绝对计数。接下来，我们通过多元回归和 ROC 分析研究了 CD19+CD25+Bregs 作为良好移植物功能的预测因子。最后，我们评估了 CD19+CD25+Bregs 与血清 IL-10、TGF-β 和 IFN-γ 之间的关系。
ESKD 患者和肾移植受者的 CD19+CD25+Bregs 计数明显低于健康对照组（p<0.001）。CD19+CD25+Breg 计数较高与肾移植受者的 GFR 较好独立相关（未标准化 B 系数=9，p=0.02）。在这些患者中，CD19+CD25+Bregs 计数较高与 Treg 计数较高独立相关（未标准化 B=2.8，p=0.004）。在 ROC 分析中，CD19+CD25+Breg 计数和血清 TGF-β1 的截断值分别为 0.12 个细胞/μl 和 19635.4 pg/ml，分别提供了良好的灵敏度和特异性，可识别 GFR≥30 ml/min（AUC=0.67，灵敏度 77%，特异性 43%；AUC=0.65，灵敏度 81%，特异性 50%）。最后，在肾移植受者中，CD19+CD25+Bregs 与 TGF-β1 之间存在显著的正相关关系（r=0.255，p=0.015）。
我们的研究结果表明，CD19+CD25+Bregs 计数较高与肾移植受者的肾功能较好和绝对 Treg 计数较高独立相关。
