Antonio Lavacca1, Roberto Presta1, Chiara Gai2, Alberto Mella1, Ester Gallo1, Giovanni Camussi2, Isabella Abbasciano1, Antonella Barreca3, Cristiana Caorsi4, Fabrizio Fop1, Maria Messina1, Maura Rossetti1, Luigi Biancone1. 1. Renal Transplant Center "A. Vercellone", Nephrology, Dialysis and Renal Transplant Division, Department of Medical Sciences, "Città della Salute e della Scienza" Hospital, University of Turin, Turin, Italy. 2. Stem Cell Laboratory, Department of Medical Sciences, University of Turin, Turin, Italy. 3. Division of Pathology, Department of Medical Sciences, "Città della Salute e della Scienza" Hospital, University of Turin, Turin, Italy. 4. Department of Medical Sciences, Immunogenetic and Transplant Biology Center, "Città della Salute e della Scienza" Hospital, University of Turin, Turin, Italy.
Abstract
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.
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.
Authors: Mélanie Daligault; Béatrice Bardy; Johan Noble; Anne Bourdin; Dominique Masson; Hamza Naciri Bennani; Mathilde Bugnazet; Paolo Malvezzi; Lionel Rostaing; Thomas Jouve Journal: Transplant Direct Date: 2021-04-22
Authors: Pascale Khairallah; Nidhi Aggarwal; Ahmed A Awan; Chandan Vangala; Medha Airy; Jenny S Pan; Bhamidipati V R Murthy; Wolfgang C Winkelmayer; Venkat Ramanathan Journal: Transpl Int Date: 2021-02-26 Impact factor: 3.842
Authors: Johan Noble; Diane Giovannini; Reda Laamech; Farida Imerzoukene; Bénédicte Janbon; Laura Marchesi; Paolo Malvezzi; Thomas Jouve; Lionel Rostaing Journal: Front Med (Lausanne) Date: 2021-12-24