Higher CD19+CD25+ Bregs are independently associated with better graft function in renal transplant recipients

BMC Nephrology

Douaa M. Sayed¹  Eman Hassan¹  Martin Zeier²  Christian Morath²  Gerhard Opelz³  Caner Süsal³  Naruemol Ekpoom³  Volker Daniel³  Eman H. Ibrahim⁴  Mostafa G. Aly⁵ 

[1] Clinical Pathology Department, South Egypt Cancer Institute, Assiut University, Asyut, Egypt;Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany;Transplantation Immunology, Institute of Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany;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;Transplantation Immunology, Institute of Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany;Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany;Nephrology Unit, Internal Medicine Department, Assiut University, Asyut, Egypt;

关键词: Bregs;    Renal transplantation;    Tregs;    GFR;   

DOI  :  10.1186/s12882-021-02374-2

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodThirty-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.ResultsESKD 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).ConclusionsOur 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.

【 授权许可】

CC BY