Undine Ariane Gerlach1, Nils Lachmann, Giuseppina Ranucci, Birgit Sawitzki, Constanze Schoenemann, Johann Pratschke, Duska Dragun, Andreas Pascher. 1. 1 Department of General, Visceral and Transplantation Surgery, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany. 2 Institute for Transfusion Medicine and HLA Typing Laboratory, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany. 3 Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany. 4 Department for Nephrology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
Abstract
BACKGROUND: Non-HLA alloantibodies and autoantibodies are involved in allograft rejection in kidney and heart transplantation. Their role in intestinal transplantation has not yet been described. We examined the development of antiangiotensin II type I receptor antibodies (anti-AT1R) and antiendothelin type A receptor antibodies associated with the clinical course and histopathological findings of intestinal transplantation recipients. METHODS: Thirty-seven patients underwent intestinal or multivisceral transplantation. Non-HLA antibodies (non-HLAabs) were screened in 29 transplant recipients. Antibody-levels greater than 12 U/L were considered positive and were evaluated retrospectively regarding rejection episodes. RESULTS: Twenty patients developed anti-AT1R and/or antiendothelin type A receptor antibodies (non-HLAabs group), 9 did not (control group). The non-HLAabs group had a higher rate of allograft rejection than controls (80% vs 55%), especially a higher rate of antibody-mediated rejections (55% vs 11%, P < 0.01) with detection of donor-specific anti-HLAabs. All rejection episodes in the non-HLAabs group appeared around the time of positive non-HLAabs detection. Five patients had acute cellular rejections at the time of non-HLAabs development, 4 had viral infections. CONCLUSIONS: Our data suggest that antibody-mediated mechanisms targeting antigens beyond HLA may trigger and accelerate immune responses. Given the possibility of pharmacologic targeting of non-HLA receptors, future studies will focus on the explanation of mechanisms how non-HLAabs may enhance rejection and affect long-term allograft survival.
BACKGROUND: Non-HLA alloantibodies and autoantibodies are involved in allograft rejection in kidney and heart transplantation. Their role in intestinal transplantation has not yet been described. We examined the development of antiangiotensin II type I receptor antibodies (anti-AT1R) and antiendothelin type A receptor antibodies associated with the clinical course and histopathological findings of intestinal transplantation recipients. METHODS: Thirty-seven patients underwent intestinal or multivisceral transplantation. Non-HLA antibodies (non-HLAabs) were screened in 29 transplant recipients. Antibody-levels greater than 12 U/L were considered positive and were evaluated retrospectively regarding rejection episodes. RESULTS: Twenty patients developed anti-AT1R and/or antiendothelin type A receptor antibodies (non-HLAabs group), 9 did not (control group). The non-HLAabs group had a higher rate of allograft rejection than controls (80% vs 55%), especially a higher rate of antibody-mediated rejections (55% vs 11%, P < 0.01) with detection of donor-specific anti-HLAabs. All rejection episodes in the non-HLAabs group appeared around the time of positive non-HLAabs detection. Five patients had acute cellular rejections at the time of non-HLAabs development, 4 had viral infections. CONCLUSIONS: Our data suggest that antibody-mediated mechanisms targeting antigens beyond HLA may trigger and accelerate immune responses. Given the possibility of pharmacologic targeting of non-HLA receptors, future studies will focus on the explanation of mechanisms how non-HLAabs may enhance rejection and affect long-term allograft survival.
Authors: Meghan H Pearl; Lucia Chen; Rim ElChaki; David Elashoff; David W Gjertson; Maura Rossetti; Patricia L Weng; Qiuheng Zhang; Elaine F Reed; Eileen Tsai Chambers Journal: Kidney Int Rep Date: 2020-09-06
Authors: Alvin P Chan; Marjorie-Anne R Guerra; Maura Rossetti; Michelle J Hickey; Robert S Venick; Elizabeth A Marcus; Suzanne V McDiarmid; Douglas G Farmer; Elaine F Reed; Laura J Wozniak Journal: Pediatr Transplant Date: 2021-02-16
Authors: Nadja Stobutzki; Stephan Schlickeiser; Mathias Streitz; Katarina Stanko; Kim-Long Truong; Levent Akyuez; Katrin Vogt; Christine Appelt; Andreas Pascher; Olga Blau; Undine A Gerlach; Birgit Sawitzki Journal: Front Immunol Date: 2019-05-07 Impact factor: 7.561