Belatacept and Autoimmune Adverse Events

Ville, Simon; Cantarovich, Diego

doi:10.1097/tp.0000000000002247

Cited by 4 publications

(2 citation statements)

References 5 publications

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“…Belatacept is widely used to avoid rejection in kidney transplantation. However, very recently, Ville and Cantarovich reported that the use of belatacept in their patient who underwent renal transplantation possibly resulted in psoriatic plaques, which progressively disappeared after stopping the use of belatacept. Thus, immunotherapy fusion proteins, despite being mostly clinically efficient, also display adverse effects …”

Section: Fusion Proteins and Mabs Targeting B7‐1mentioning

confidence: 99%

Targeting B7‐1 in immunotherapy

Chen

Okoye

Arutyunova

et al. 2019

Medicinal Research Reviews

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Modulation of T‐cell immune functions by blocking key immune checkpoint protein interactions using monoclonal antibodies (mAbs) has been an innovative immunotherapeutic strategy. T‐cells are regulated by different checkpoint proteins at the immunological synapse including the B7 ligands (B7‐1 or CD80 and B7‐2 or CD86), which is discussed in this review. These ligands are typically expressed on antigen presenting cells and interact with CD28 and cytotoxic T lymphocyte antigen‐4 (CTLA‐4) receptors on T‐cells. Their interactions with CD28 trigger a costimulatory signal that potentiates T‐cell activation, function and survival in response to cognate antigen. In addition, their interactions with CTLA‐4 can also inhibit certain effector T‐cell responses, particularly in response to sustained antigen stimulation. Through these mechanisms, the balance between T‐cell activation and suppression is maintained, preventing the occurrence of immunopathology. Given their crucial roles in immune regulation, targeting B7 ligands has been an attractive strategy in cancer and autoimmunity. This review presents an overview of the essential roles of B7‐1, highlighting the therapeutic benefits of modulating this protein in immunotherapy, and reviewing earlier and state‐of‐the‐art efforts in developing anti‐B7‐1 inhibitors. Finally, we discuss the challenges facing the design of selective B7‐1 inhibitors and present our perspectives for future developments.

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Section: Fusion Proteins and Mabs Targeting B7‐1mentioning

confidence: 99%

Targeting B7‐1 in immunotherapy

Chen

Okoye

Arutyunova

et al. 2019

Medicinal Research Reviews

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“…Belatacept was shown to have superior renal function and similar 12-month patient and graft survival to cyclosporine [7]. However, trial data also showed increased acute cellular rejection within the first-year post-transplant [8], with other reports linking CTLA-4 inhibitors with new onset psoriasis [9] and chilblain lupus [10]. Though the exact mechanisms behind these pro-inflammatory phenomena remain unknown, several theories may explain the reactivation of AAV in our patient, and formed the basis for conversion to tacrolimus, without subsequent AAV recurrence.…”

Section: Discussionmentioning

confidence: 95%

Early post-transplant recurrence of ANCA vasculitis while on belatacept maintenance immunosuppression

et al. 2023

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Post-transplant recurrence of ANCA-associated vasculitis (AAV) is infrequent, with recurrence within weeks of transplantation being even rarer. We describe an unusual case of AAV recurrence within 2 weeks post-transplant. Our patient received a deceased donor kidney transplant (KDPI 60%) after 6 years on hemodialysis for end-stage renal disease from AAV. She was induced with thymoglobulin and steroids, and maintained on belatacept, mycophenolate and prednisone. Time-zero biopsy showed acute tubular injury. Due to persistent delayed graft function by post-operative day 14, she underwent repeat biopsy, which showed focal segmental necrotizing and crescentic glomerulonephritis, with positive MPO, PR3 and negative anti-glomerular basement membrane antibodies. As her findings were in keeping with recurrent AAV, she underwent induction with rituximab, prednisone and intravenous immunoglobulin, with repeat rituximab 14 days later because of increasing B-lymphocyte counts. Belatacept was replaced with tacrolimus due to concerns with autoimmunity. Fortunately, renal function began to recover 4 days after treatment. In addition to highlighting potential immunologic mechanisms in AAV and the use of rituximab in post-transplant recurrence, our case suggests that for systemic autoimmune disease, patients maintained on belatacept must be monitored closely for recurrence, particularly in the setting of delayed graft function. Graphical Abstract

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