Type-II-CD20-targeted therapy for CD38 antibody-refractory antibody-mediated rejection after kidney transplantation: a case report.

With the advent of CD38 antibody therapy, an effective treatment option for antibody-mediated rejection (ABMR) appears achievable. However, a subset of patients remains refractory. We report a kidney transplant recipient with persistent microvascular inflammation in kidney allograft biopsy after six months of CD38 antibody treatment, necessitating rescue therapy. Persistent detection of peripheral CD38-negative class-switched memory B cells prompted additional deep B-cell depletion using a humanized, glycoengineered, IgG1 monoclonal antibody targeting the type-II epitope of CD20. Follow-up kidney biopsy demonstrated histological resolution of microvascular inflammation, while normalization of donor-derived cell-free DNA was consistent with remission of ABMR. In this case of CD38 antibody-refractory ABMR, adjunctive type-II-CD20 antibody therapy had a favorable response. This highlights the potential contribution of additional effector cells to refractory ABMR, such as CD38-negative class-switched memory B cells. These findings suggest a potential role for individualized, multimodal B-cell-directed immunomodulatory strategies that may improve outcomes in selected patients with treatment-refractory ABMR, thus contributing to sustained allograft survival.