B-Cell Activating Factor Predicts Acute Rejection Risk in Kidney Transplant Recipients: A 6-Month Follow-Up Study

Abstract

B cell activating factor (BAFF) belonging to TNF family is a cytokine that enhances B-cell proliferation and differentiation. Recently, It has been suggested that BAFF might be a potential therapeutic target for treating autoimmune disease. However, the relationship between BAFF and allograft rejection is controversial, and the clinical significance of BAFF in predicting allograft rejection need to be further explored. We conducted 6-month follow-up study to confirm the hypothesis that BAFF might be a risk factor for predicting acute rejection in kidney transplant recipients. At the end of the study, a total of 155 kidney transplant recipients were recruited from October 2015 to October 2017, and classified into acute rejection group ( n = 34) and stable renal function group ( n = 121) according to their clinical course. We demonstrate that the serum BAFF levels when acute rejection occurred was significantly higher than that in the stable renal function group (2426.19 ± 892.19 vs. 988.17 ± 485.63 pg/mL, P < 0.05). BAFF expression was significantly enhanced in the membrane and cytoplasm of renal tubule epithelial cells in the transplant kidney tissue with acute rejection, and a positive correlation between BAFF and C4d expression was also observed ( r = 0.880, P = 0.001). ROC analyses highlight the superiority of serum BAFF level before transplant over those on other post-transplant days in prediction of acute rejection episodes. The sensitivity, specificity and AUC (area under curve) were 83.3, 89.5, and 0.886%, respectively. Kaplan-Meier survival analysis showed that recipients with higher pretransplant BAFF levels had higher acute rejection incidence ( P = 0.003). In conclusion, we have identified that BAFF levels are associated with the acute rejection and could be a promising biomarker to predict kidney transplant rejection risks.

High Pretransplant BAFF Levels and B-cell Subset Polarized towards a Memory Phenotype as Predictive Biomarkers for Antibody-Mediated Rejection

“…Unlike the results showed by different groups where no differences were found in BAFF levels between kidney transplant recipients and controls [31] indicating that this molecule is not a prognostic marker for allograft dysfunction, or that no correlation exists between BAFF and the production of DSA before and after transplantation [32], in the present study we observed that patients with AbMR presented higher levels of BAFF before transplantation, being also elevated BAFF serum levels in those patients with anti-HLA antibodies and DSA. These results are in a relationship published by other authors showing that BAFF is associated with allograft survival [37], acute antibody-mediated rejection as well as the presence of DSA [28,29,38]. A meta-analysis published recently also corroborates our results, indicating that the incidence of antibody-mediated rejection is higher in those patients with higher levels of serum BAFF.…”

“…We also observed that serum BAFF levels, measured at 6 and at 12 months after transplantation were also higher in those patients with subclinical antibody-mediated rejection detected in the surveillance biopsy, corroborating the possible contribution of BAFF to the pathogenesis of antibody-mediated graft damage. Considering this aspect, Won Min et al described that while pretransplant BAFF levels showed significant association with early rejection, posttransplant BAFF levels measured at the time of indication biopsy are not associated with allograft rejection [25].It is important to highlight some relevant aspects of our study such as the prospective monitoring of the kidney transplant patients at 6 and at 12 months after kidney transplantation, which differentiates it from other transversal studies or with a shorter period of follow-up [28,29]. In the same way we would like to emphasize the importance of surveillance biopsy that gives up data about the possible existence of a subclinical rejection.…”

“…However, in the context of transplantation, there are less studies and the role of BAFF is more controversial. On the one hand, some authors indicate that BAFF reflects the immunological risk profile of patients after kidney transplantation (KT), considering that pretransplant BAFF levels are associated with pretransplant sensitization and are useful in predicting allograft rejection [23][24][25]; BAFF expression correlates with pretransplant panel reactive antibody (PRA), indicating that BAFF may be involved in the development of graft loss [26]; elevated levels of BAFF are associated with antibody-mediated clinical damage in KT [27], and with an increased risk of acute AbMR [28][29][30]. On the other hand, there are authors that affirm that BAFF is not a prognostic marker for allograft dysfunction or survival in KT patients because BAFF serum levels are not related to anti-HLA sensitization [31]; significantly lower levels of BAFF are found in patients experiencing AbMR [32]; or high BAFF is not associated with the graft outcome in KT with rituximab induction [33].…”

Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection

“…2f). TNFR13B encodes TACI, a receptor for BAFF overexpression of which is associated with renal allograft rejection 31,32 .…”

Intrarenal B cells integratein situinnate and adaptive immunity in human renal allograft rejection

“…BAFF mediates B cell survival and is important in some B-cell-mediated inflammatory diseases (Davidson, 2010). Furthermore, BAFF over-expression is associated with renal allograft rejection (Pongpirul et al, 2018;Wang et al, 2019). Therefore, the high expression of TACI in intrarenal B cells suggests a role in in situ activation and survival.…”