Emerging New Approaches in Desensitization: Targeted Therapies for HLA Sensitization

Abstract

There is an urgent need for therapeutic interventions for desensitization and antibody-mediated rejection (AMR) in sensitized patients with preformed or de novo donor-specific HLA antibodies (DSA). The risk of AMR and allograft loss in sensitized patients is increased due to preformed DSA detected at time of transplant or the reactivation of HLA memory after transplantation, causing acute and chronic AMR. Alternatively, de novo DSA that develops post-transplant due to inadequate immunosuppression and again may lead to acute and chronic AMR or even allograft loss. Circulating antibody, the final product of the humoral immune response, has been the primary target of desensitization and AMR treatment. However, in many cases these protocols fail to achieve efficient removal of all DSA and long-term outcomes of patients with persistent DSA are far worse when compared to non-sensitized patients. We believe that targeting multiple components of humoral immunity will lead to improved outcomes for such patients. In this review, we will briefly discuss conventional desensitization methods targeting antibody or B cell removal and then present a mechanistically designed desensitization regimen targeting plasma cells and the humoral response.

Successful ABO‐incompatible living donor kidney transplantation in a recipient who developed flow cytometry crossmatch‐positive donor‐specific class I HLA antibodies following COVID‐19 vaccination

“…After seven replicates of PP and pretransplant immunosuppression, DSA level was paradoxically increased (anti-A24 8342, anti-B51 5828, and anti-Cw14 7081). Although rebound in DSA has been reported after short-term PP, 20 our patient showed an unexpected increase in HLA antibodies (MFI-sum of 21,251). This might be because of the synergistic effect of humoral immune reactivation by vaccination.…”

Case report: Successful combination therapy with double-filtration plasmapheresis and rituximab under the condition of the use of a sensor-augmented pump for type B insulin resistance syndrome

“…Since the patient had progressive weight loss and muscle wasting, DFPP was used as an acute-phase therapy to prevent catabolism by restoring insulin sensitivity via removal of antiinsulin receptor antibodies. Actually, DFPP has been applied to various conditions including autoimmune diseases and organ transplantations (12,17,18). Since TBIR has been reported to be…”

B Cell Immunity in Lung Transplant Rejection - Effector Mechanisms and Therapeutic Implications

“…Plasmapheresis and immunoadsorption are often employed to reduce circulating DSA in highly sensitized recipients ( 89 ). While plasmapheresis separates plasma from whole blood, immunoadsorption specifically removes target antibodies from the circulation.…”