High B‐cell activating factor is not associated with worse 3‐year graft outcome in blood group‐incompatible kidney transplantation with rituximab induction

Abstract

B cells and their regulation by B-cell activating factor BAFF are of growing interest in kidney transplantation (KTx). There is evidence that high serum (s) BAFF leads to increased allosensitization and impaired long-term graft function. We prospectively investigated sBAFF, peripheral blood lymphocytes (PBL), and donor-specific HLA antibodies (DSA) in patients after ABOi with B-cell depleting rituximab induction treatment and compared them to a group of blood group-compatible (ABOc) living donor kidney recipients. Twelve patients after ABOi and 18 after ABOc were included. After rituximab treatment prior to ABOi, B cells remained significantly lower 1 year after KTx (1.2% (0.0-17.8) compared to ABOc of 8.6% (2.8-35.0), p = 0.0004, and also BAFF-R expression was significantly lower in ABOi (p < 0.006). sBAFF remained elevated 1 year post-Tx compared to ABOc (3615 ± 1800 vs. 1394 ± 493 pg/mL, p < 0.004). Kidney function was not significantly different between both groups after 1, 2, and 3 years. The use of rituximab in ABOi together with maintenance immunosuppression leads to significant elevation of sBAFF and lowering of B-cell numbers for more than 1 year, and this does not correlate with worse 3-year graft outcome.

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

“…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]. A meta-analysis published recently evaluated the predictive value of serum BAFF for AbMR, indicating that the incidence of AbMR was significantly higher in patients with high levels of BAFF [34].…”

Clinical Significance of Pre- and Post-Transplant BAFF Levels in Kidney Transplant Recipients

“…According to our center’s desensitization protocols, pre-sensitized patients with high PRA or positive HLA-DSA are treated with rituximab (375 mg/m 2 , intravenously) a month before transplantation. B-cell depleting agents such as this have been reported to be associated with significant elevation of serum BAFF levels for more than 1 year after transplantation [ 16 , 21 , 22 ]. Comparison of post-transplant serum BAFF levels in patients who underwent Rituximab therapy and those who did not, showed that post-transplant BAFF levels were significantly higher in patients who underwent Rituximab therapy (median 251.48 pg/mL vs. 80.73 pg/mL in patients without Rituximab therapy, P = 0.000) ( S3A Fig ).…”