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.
Highlights
The role of B-cells in kidney transplantation has been highlighted in recent studies [1], especially in transplantation tolerance and antibody-mediated rejection (AMR) [2, 3]
We found that the serum BAFF level was 2426.19 ± 892.19 pg/mL (95% confidence interval: 1489.89∼3362.49 pg/ml) at the time of acute rejection, significantly higher than that in the stable renal function group (988.17 ± 485.63 pg/mL, P< 0.05) and healthy controls (898.10 ± 269.74 pg/mL, P < 0.05) (Figure 1)
Recent reports has demonstrated that BAFF is associated with acute antibody-mediated rejection [14] and allograft survival [15, 16], and might be a predictor of antibody mediated rejection in kidney transplantation recipients [11]
Summary
The role of B-cells in kidney transplantation has been highlighted in recent studies [1], especially in transplantation tolerance and antibody-mediated rejection (AMR) [2, 3]. B cell activating factor (BAFF) belonging to TNF family is a cytokine that enhances B-cell survival and proliferation [3]. It participates in many processes involved in B cell regulation, such as activation, proliferation, antibody production and immunoglobulin class switching [5]. BAFF is a key factor for the survival of B cells and homeostasis [6]. BAFF excess might contribute to the abnormal rescue of self-reactive and might be a key role in B-cell dysregulation [7]
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