BACKGROUND: Non-human leukocyte antigen antibodies (Abs) targeting vascular receptors are implicated in the pathogenesis of renal allograft vascular rejection and in progressive vasculopathy in patients with systemic sclerosis. METHODS: We prospectively tested in 30 heart transplant recipients the impact of Abs directed against endothelin-1 type A (ET(A)R) and angiotensin II type 1 receptors (AT(1)R, cell-enzyme-linked immunosorbent assay) at time of transplantation and during the first posttransplantation year on cellular and Ab-mediated rejection (immunohistochemistry, C3d, and immunoglobulins) and microvasculopathy in endomyocardial biopsy. RESULTS: Cellular rejection, Ab-mediated rejection, and microvasculopathy was found in 40% and 13%, 57% and 18%, and 37% and 40% of biopsies at 1 month and 1 year posttransplantation, respectively. Maximum levels of AT(1)R and ET(A)R Abs were higher in patients with cellular (16.5±2.6 vs. 9.4±1.3; P=0.021 and 16.5±2.5 vs. 9.9±1.9; P=0.041) and Ab-mediated rejection (19.0±2.6 vs. 10.0±1.3; P=0.004 and 19.4±2.7 vs. 9.0±1.7; P=0.002), as compared with patients who had no rejection. Patients with elevated AT(1)R Abs (53% [16/30]) or ETAR Abs (50% [15/30]; pretransplantation prognostic rejection cutoff >16.5 U/L) presented more often with microvasculopathy (both, 67% vs. 23%; P=0.048) than patients without. CONCLUSIONS: Elevated levels of AT(1)R and ET(A)R Abs are associated with cellular and Ab-mediated rejection and early onset of microvasculopathy and should be routinely monitored after heart transplantation.
BACKGROUND: Non-human leukocyte antigen antibodies (Abs) targeting vascular receptors are implicated in the pathogenesis of renal allograft vascular rejection and in progressive vasculopathy in patients with systemic sclerosis. METHODS: We prospectively tested in 30 heart transplant recipients the impact of Abs directed against endothelin-1 type A (ET(A)R) and angiotensin II type 1 receptors (AT(1)R, cell-enzyme-linked immunosorbent assay) at time of transplantation and during the first posttransplantation year on cellular and Ab-mediated rejection (immunohistochemistry, C3d, and immunoglobulins) and microvasculopathy in endomyocardial biopsy. RESULTS: Cellular rejection, Ab-mediated rejection, and microvasculopathy was found in 40% and 13%, 57% and 18%, and 37% and 40% of biopsies at 1 month and 1 year posttransplantation, respectively. Maximum levels of AT(1)R and ET(A)R Abs were higher in patients with cellular (16.5±2.6 vs. 9.4±1.3; P=0.021 and 16.5±2.5 vs. 9.9±1.9; P=0.041) and Ab-mediated rejection (19.0±2.6 vs. 10.0±1.3; P=0.004 and 19.4±2.7 vs. 9.0±1.7; P=0.002), as compared with patients who had no rejection. Patients with elevated AT(1)R Abs (53% [16/30]) or ETAR Abs (50% [15/30]; pretransplantation prognostic rejection cutoff >16.5 U/L) presented more often with microvasculopathy (both, 67% vs. 23%; P=0.048) than patients without. CONCLUSIONS: Elevated levels of AT(1)R and ET(A)R Abs are associated with cellular and Ab-mediated rejection and early onset of microvasculopathy and should be routinely monitored after heart transplantation.
Authors: T Puehler; S Ensminger; U Schulz; U Fuchs; K Tigges-Limmer; J Börgermann; M Morshuis; K Hakim; O Oldenburg; J Niedermeyer; A Renner; J Gummert Journal: Herz Date: 2014-02 Impact factor: 1.443
Authors: Sarah B See; Benjamin S Mantell; Kevin J Clerkin; Bryan Ray; E Rodica Vasilescu; Charles C Marboe; Yoshifumi Naka; Susan Restaino; Paolo C Colombo; Linda J Addonizio; Maryjane A Farr; Emmanuel Zorn Journal: Am J Transplant Date: 2020-04-26 Impact factor: 8.086
Authors: Marianne Delville; Baptiste Lamarthée; Sylvain Pagie; Sarah B See; Marion Rabant; Carole Burger; Philippe Gatault; Magali Giral; Olivier Thaunat; Nadia Arzouk; Alexandre Hertig; Marc Hazzan; Marie Matignon; Christophe Mariat; Sophie Caillard; Nassim Kamar; Johnny Sayegh; Pierre-François Westeel; Cyril Garrouste; Marc Ladrière; Vincent Vuiblet; Joseph Rivalan; Pierre Merville; Dominique Bertrand; Alain Le Moine; Jean-Paul Duong Van Huyen; Anne Cesbron; Nicolas Cagnard; Olivier Alibeu; Simon C Satchell; Christophe Legendre; Emmanuel Zorn; Jean-Luc Taupin; Béatrice Charreau; Dany Anglicheau Journal: J Am Soc Nephrol Date: 2019-03-08 Impact factor: 10.121