Monitoring of B Cell in Kidney Transplantation: Development of a Novel Clusters Analysis and Role of Transitional B Cells in Transplant Outcome

Abstract

Background: B lymphocytes (BL) seem to play an important role in transplantation, although the and role of different subpopulations in monitoring and outcome is not clear. Our aim was to monitoring immunological profiles based on BL subpopulations in kidney recipients (KR) with the risk of acute rejection (AR). Methods: Monitoring of BL subpopulations was performed by flow cytometry in PBLs before transplantation and three and six months after transplantation (PTX). We used two methodological approaches, a traditional analysis, and a novel cluster analysis, to determine the association between BL subpopulations, AR incidence, and graft function. Results: After three months of PTX, KRs with a B phenotype enriched in transitional BL and plasmablasts had better kidney function and lower AR incidence. KRs with decreased transitional BL and plasmablasts were associated with lower kidney function and higher AR PTX. KRs that had an increase in transitional BL PTX had a better clinical outcome. The increase in transitory BL during PTX was also associated with an increase in Tregs. Indeed, KRs receiving thymoglobulin as induction therapy showed a slight decrease in the relative frequency of naive BLs after three months of PTX. Conclusion: The monitoring of BL subpopulations may serve as a non-invasive tool to improve immunological follow-up of patients after kidney transplantation. However, further studies are needed to confirm the obtained results, define cut-off values, and standardize more optimal and even custom/customized protocols.

B Cell Composition Is Altered After Kidney Transplantation and Transitional B Cells Correlate With SARS-CoV-2 Vaccination Response

“…In accordance with the existing literature, we have also seen a reduction of TrBCs in the post-transplantation setting (32,65). Low TrBCs have been considered as potential biomarkers for graft rejection (7,8), and tolerant KTRs display a high frequency of TrBCs (29).…”

Maternal, Decidual, and Neonatal Lymphocyte Composition Is Affected in Pregnant Kidney Transplant Recipients

“…Although calcineurin inhibitors such as tacrolimus can inhibit B cell differentiation in vitro (52), kidney transplant recipients with a B cell phenotype enriched for plasmablasts have a better transplant prognosis, i.e. better renal function and lower acute rejection incidence (53). In contrast, increased frequencies of B cells with a memory phenotype (CD27 + CD38 +/-) could be observed in the circulation of preeclamptic women (54,55), suggesting that while the observed phenotypes could be beneficial for transplant survival they could be associated with the increased risk of complications in pregnant kidney transplant recipients.…”

Computational Prediction of Biomarkers, Pathways, and New Target Drugs in the Pathogenesis of Immune-Based Diseases Regarding Kidney Transplantation Rejection

“…The Kruskal Wallis test and Dunn’s post hoc test with Bonferroni correction for multiple comparisons compared three or more groups. Correlation analyzes were carried out using the Spearman index, as previously published ( 5 , 21 , 22 ). For the longitudinal comparison of two related groups, the Wilcoxon non-parametric test for related samples was used.…”