Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation

Abstract

The long-term effect of rituximab and splenectomy on de novo HLA antibody production and chronic antibody-mediated rejection after renal transplantation is uncertain. In order to gain insight on this, we studied 92 ABO-incompatible and 228 ABO-identical/compatible consecutive renal transplant patients and determined their de novo HLA antibody production and graft outcome. Patients with pretransplant donor-specific antibodies had been excluded. ABO-incompatible transplants included 30 recipients treated with rituximab, 51 by splenectomy, or 11 with neither, due to low anti-A or -B antibody titer. Graft survival in ABO-identical/compatible patients (97.7% at 5 years) was significantly higher than in ABO-incompatible (87.0% at 5 years), rituximab (96.7% at 3 years), or splenectomy (85.7% at 5 years) patients. Only four patients had clinical chronic antibody-mediated rejection (two each identical/compatible and incompatible). There was no significant difference in prevalence of de novo HLA antibody, including donor-specific and nondonor-specific antibodies among ABO-identical/compatible patients (13.9%), patients receiving rituximab (14.3%) or splenectomy (13.2%), or among those receiving cyclosporine, tacrolimus, mycophenolate mofetil, mizoribine, and everolimus. Renal function remained stable in most recipients with de novo HLA antibody. Thus, neither pretransplant splenectomy nor rituximab treatment has an inhibitory effect on de novo HLA antibody production during medium-term follow-up. Further study on long-term effects is needed.

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

“…We acknowledge that our number of patients is limited, but we observed the same rate of de novo HLA‐DSA in ABOi as in ABOc despite B‐cell depleting therapy, supporting data by Ashimine et al. . Further investigations are needed to assess whether the BAFF effect is limited or delayed in patients after rituximab treatment with very low peripheral B cells and reduced BAFF‐R expression.…”

Different sensitivity of rituximab-treatment to B-cells between ABO-incompatible kidney and liver transplantation

“…Consistently, in both KT and LT, the incidences of AR and the appearance of dnDSA were not significantly different between the ABO-I and ABO-C groups. One study reported that the percentage of dnDSA production was significantly lower in ABO-I KT recipients treated with rituximab than in ABO-C KT recipients [27], whereas another study reported that the prevalence of dnDSA was not significantly different between ABO-I and ABO-C KT recipients [28]. To clarify these results, a prospective randomized trial that compares the effect of rituximab therapy in ABO-I and ABO-C recipients is needed.…”

An update on ABO-incompatible kidney transplantation

“…More recent reports now challenge the assumption that B‐cell depletion is essential to prevent antibody‐mediated rejection , for example some centres started to routinely perform ABOi KTx without rituximab . However, there has been evidence that there is less chronic antibody‐mediated rejection (AMR) when rituximab is being used .…”