Approaches for Controlling Antibody-Mediated Allograft Rejection Through Targeting B Cells

Abstract

Both acute and chronic antibody-mediated allograft rejection (AMR), which are directly mediated by B cells, remain difficult to treat. Long-lived plasma cells (LLPCs) in bone marrow (BM) play a crucial role in the production of the antibodies that induce AMR. However, LLPCs survive through a T cell-independent mechanism and resist conventional immunosuppressive therapy. Desensitization therapy is therefore performed, although it is accompanied by severe side effects and the pathological condition may be at an irreversible stage when these antibodies, which induce AMR development, are detected in the serum. In other words, AMR control requires the development of a diagnostic method that predicts its onset before LLPC differentiation and enables therapeutic intervention and the establishment of humoral immune monitoring methods providing more detailed information, including individual differences in the susceptibility to immunosuppressive agents and the pathological conditions. In this study, we reviewed recent studies related to the direct or indirect involvement of immunocompetent cells in the differentiation of naïve-B cells into LLPCs, the limitations of conventional methods, and the possible development of novel control methods in the context of AMR. This information will significantly contribute to the development of clinical applications for AMR and improve the prognosis of patients who undergo organ transplantation.

Utility of Routine Post Kidney Transplant Anti-HLA Antibody Screening

“…The aim of annual screening for anti-HLA antibodies is to detect dnDSA before the presence of AMR lesions or at very early stages of AMR. 13 , 31 However, despite a better death-censored graft survival, our data do not perfectly support this idea, because we observed acute and chronic histological AMR features in patients that received a biopsy after dnDSA detection during systematic screening. Lesions of transplant glomerulopathy, illustrated by a cg score >0 were seen in up to 15% of biopsies in this group, similar to what was observed in the clinically indicated group.…”

Repurposing of rituximab biosimilars to treat B cell mediated autoimmune diseases

“…AMR is a leading cause of morbidity and mortality following transplant surgery 135 . In AMR, B cells from the donor produce antibodies against antigens expressed on recipient organ cells 136–146 . Rituximab administration before transplantation, with or without follow‐up maintenance doses, improved AMR and graft survival rates in patients undergoing kidney transplantation 147 .…”

“…135 In AMR, B cells from the donor produce antibodies against antigens expressed on recipient organ cells. [136][137][138][139][140][141][142][143][144][145][146] Rituximab administration before transplantation, with or without follow-up maintenance doses, improved AMR and graft survival rates in patients undergoing kidney transplantation. 147 Similarly, rituximab may also improve clinical responses and quality of life in patients who develop steroid-refractory chronic graft-versus-host disease after allogeneic stem cell transplantation.…”

Repurposing of rituximab biosimilars to treat B cell mediated autoimmune diseases

“…149 In AMR, B cells from the donor produce antibodies against antigens expressed on recipient organ cells. [150][151][152][153][154][155][156][157][158][159][160] Rituximab administration before transplantation, with or without follow-up maintenance doses, improved AMR and graft survival rates in patients undergoing kidney transplantation. 161 Similarly, rituximab may also improve clinical responses and quality of life in patients who develop steroid-refractory chronic graftversus-host disease after allogeneic stem cell transplantation.…”