M Banasik1, M Boratyńska2, K Kościelska-Kasprzak2, D Kamińska2, S Zmonarski2, O Mazanowska2, M Krajewska2, D Bartoszek2, M Zabińska2, M Myszka2, M Kamińska3, A Hałoń4, T Dawiskiba5, P Szyber5, A Sas2, M Klinger2. 1. Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland. Electronic address: m.banasik@interia.pl. 2. Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland. 3. Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wroclaw, Poland. 4. Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland. 5. Department of Vascular, General and Transplantation Surgery, Wroclaw Medical University, Wroclaw, Poland.
Abstract
INTRODUCTION: Non-HLA antibodies specific for angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) of vascular cells activate signaling pathways leading to cell proliferation and vascular injury. The aim of this study was to evaluate the impact of non-HLA antibodies on kidney allograft morphology and function in patients who underwent a kidney biopsy due to renal function impairment. PATIENTS AND METHODS: The study included 65 consecutive renal transplant patients who were evaluated for the presence of non-HLA and anti-HLA antibodies at the time of transplant biopsy. Results of pre-transplant CDC cross-match were negative. A kidney allograft biopsy was performed between 6 days and 13 years (42 ± 49 months) after transplantation, and the diagnosis was made on the basis of the Banff criteria. The level >9 U/L of anti-AT1R and anti-ETAR antibodies was considered high. RESULTS: A high level of non-HLA antibodies (anti-AT1R and/or anti-ETAR) was found in 7 (10.7%) of 65 patients at the time of biopsy. Graft loss in the non-HLA-positive patients was significantly higher (71% in non-HLA-positive cases after 7.8 ± 2.6 months vs 11% after 6 months in non-HLA-negative cases [P = .00099]). In these non-HLA-positive patients, the mean anti-AT1R level was 15.3 ± 9.4 U/L and the mean anti-ETAR level was 13.8 ± 8.6 U/L. In only 2 of these patients were anti-HLA antibodies additionally detected: anti-class I in 1 and anti-class II in both patients. The mean serum creatinine level was 2.34 ± 0.6 mg/dL at the time of biopsy. Results of an early biopsy revealed acute vascular rejection (Banff grade IIB). Chronic allograft injury was found (grading cg1-3, cv1-2, ci1-2, ct1-2) in the remaining 6 patients. C4d was present in 3 of 7 patients. CONCLUSIONS: High levels of anti-AT1R and/or anti-ETAR antibodies were associated with morphological and functional allograft injury and graft loss in these study patients. Non-HLA antibodies can be helpful in assessing the risk of graft failure.
INTRODUCTION: Non-HLA antibodies specific for angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) of vascular cells activate signaling pathways leading to cell proliferation and vascular injury. The aim of this study was to evaluate the impact of non-HLA antibodies on kidney allograft morphology and function in patients who underwent a kidney biopsy due to renal function impairment. PATIENTS AND METHODS: The study included 65 consecutive renal transplant patients who were evaluated for the presence of non-HLA and anti-HLA antibodies at the time of transplant biopsy. Results of pre-transplant CDC cross-match were negative. A kidney allograft biopsy was performed between 6 days and 13 years (42 ± 49 months) after transplantation, and the diagnosis was made on the basis of the Banff criteria. The level >9 U/L of anti-AT1R and anti-ETAR antibodies was considered high. RESULTS: A high level of non-HLA antibodies (anti-AT1R and/or anti-ETAR) was found in 7 (10.7%) of 65 patients at the time of biopsy. Graft loss in the non-HLA-positive patients was significantly higher (71% in non-HLA-positive cases after 7.8 ± 2.6 months vs 11% after 6 months in non-HLA-negative cases [P = .00099]). In these non-HLA-positive patients, the mean anti-AT1R level was 15.3 ± 9.4 U/L and the mean anti-ETAR level was 13.8 ± 8.6 U/L. In only 2 of these patients were anti-HLA antibodies additionally detected: anti-class I in 1 and anti-class II in both patients. The mean serum creatinine level was 2.34 ± 0.6 mg/dL at the time of biopsy. Results of an early biopsy revealed acute vascular rejection (Banff grade IIB). Chronic allograft injury was found (grading cg1-3, cv1-2, ci1-2, ct1-2) in the remaining 6 patients. C4d was present in 3 of 7 patients. CONCLUSIONS: High levels of anti-AT1R and/or anti-ETAR antibodies were associated with morphological and functional allograft injury and graft loss in these study patients. Non-HLA antibodies can be helpful in assessing the risk of graft failure.
Authors: Nicholas J Steers; Yifu Li; Zahida Drace; Justin A D'Addario; Clara Fischman; Lili Liu; Katherine Xu; Young-Ji Na; Y Dana Neugut; Jun Y Zhang; Roel Sterken; Olivia Balderes; Drew Bradbury; Nilgun Ozturk; Fatih Ozay; Sanya Goswami; Karla Mehl; Jaclyn Wold; Fatima Z Jelloul; Mersedeh Rohanizadegan; Christopher E Gillies; Elena-Rodica M Vasilescu; George Vlad; Yi-An Ko; Sumit Mohan; Jai Radhakrishnan; David J Cohen; Lloyd E Ratner; Francesco Scolari; Katalin Susztak; Matthew G Sampson; Silvia Deaglio; Yasar Caliskan; Jonathan Barasch; Aisling E Courtney; Alexander P Maxwell; Amy J McKnight; Iuliana Ionita-Laza; Stephan J L Bakker; Harold Snieder; Martin H de Borst; Vivette D'Agati; Antonio Amoroso; Ali G Gharavi; Krzysztof Kiryluk Journal: N Engl J Med Date: 2019-05-16 Impact factor: 91.245
Authors: Kevin Budding; Eduard A van de Graaf; Tineke Kardol-Hoefnagel; Erik-Jan D Oudijk; Johanna M Kwakkel-van Erp; C Erik Hack; Henny G Otten Journal: Front Immunol Date: 2017-03-21 Impact factor: 7.561