Tocilizumab in kidney transplant recipients with caAMR

Kidney transplantation (KT) is the treatment of choice for patients with end-stage renal disease (ESRD), offering significant improvements in survival and quality of life. Despite advances in short-term graft survival, long-term outcomes remain suboptimal, with chronic active antibody-mediated rejection (cAMR) representing a major cause of late graft loss, primarily driven by donor-specific anti-HLA antibodies (DSA). Diagnosis of cAMR relies on both laboratory and histological criteria, including the presence of DSA and microvascular lesions with or without C4d deposition. Current therapies effective in acute AMR have shown limited benefit in cAMR, highlighting the need for novel strategies. Interleukin-6 (IL-6) plays a pivotal role in inflammation and in the activation of B and T lymphocytes and plasma cells, promoting antibody production. Tocilizumab (TCZ), a humanized monoclonal antibody targeting both soluble and membrane-bound IL-6 receptors, is approved for autoimmune diseases and may offer a promising approach for alloimmune modulation in transplantation. This observational study, combining prospective and retrospective components, was primarily conducted at a single center with a multicenter extension through collaboration with the Grenoble Transplant Center. The primary objective was to assess renal function in KT recipients with cAMR following TCZ therapy, while secondary endpoints included histomorphological, biohumoral, and cytological evaluations. By inhibiting IL-6 signaling, TCZ may reduce DSA titers, attenuate microvascular inflammation, and improve long-term graft survival, addressing a critical unmet need in transplantation medicine.