Journal
CLINICAL TRANSPLANTATION
Volume 34, Issue 8, Pages -Publisher
WILEY
DOI: 10.1111/ctr.13908
Keywords
angiotensin II type I-receptor antibody; anti-HLA antibody; chronic antibody-mediated rejection; donor-specific antibodies; kidney transplantation; tocilizumab; transplant glomerulopathy
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Funding
- Universita degli Studi di Torino [CAMGAUTO14]
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Introduction Chronic active antibody-mediated rejection (cAMR) is a major determinant of late allograft failure. Rituximab/immunoglobulins (IVIg) + plasma exchange (PLEX) showed controversial results in cAMR treatment. Tocilizumab (TCZ), a humanized anti-interleukin 6 receptor antibody, has been recently used as rescue therapy in patients non-responsive to rituximab/IVIg/PLEX with favorable outcomes. Whether TCZ acts per se or requires a priming effect from previous treatments is currently unknown. Methods Fifteen patients with cAMR were treated with TCZ as a first-line therapy and followed for a median time of 20.7 months. Results Despite the majority of patients experiencing advanced transplant glomerulopathy (TG) at diagnosis (60% with cg3), glomerular filtration rate and proteinuria stabilized during the follow-up, with a significant reduction in donor-specific antibodies. Protocol biopsies after 6 months demonstrated significant amelioration of microvascular inflammation and no TG, C4d deposition, or IF/TA progression. Gene-expression and immunofluorescence analysis showed upregulation of three genes (TJP-1, AKR1C3, and CASK) involved in podocyte, mesangial, and tubular restoration. Conclusion Tocilizumab adopted as a first-line approach in cAMR was associated with early serological and histological improvements and functional stabilization even in advanced TG, suggesting a role for the use of TCZ alone with the avoidance of unnecessary previous immunosuppressants.
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