Non-HLA antibodies: angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) are associated with renal allograft injury and graft loss.
BACKGROUND
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.


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.
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland. Electronic address: m.banasik@interia.pl.
M
M
Banasik
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
M
M
Boratyńska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
K
K
Kościelska-Kasprzak
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
D
D
Kamińska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
S
S
Zmonarski
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
O
O
Mazanowska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
M
M
Krajewska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
D
D
Bartoszek
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
M
M
Zabińska
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
M
M
Myszka
Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wroclaw, Poland.
M
M
Kamińska
Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland.
A
A
Hałoń
Department of Vascular, General and Transplantation Surgery, Wroclaw Medical University, Wroclaw, Poland.
T
T
Dawiskiba
Department of Vascular, General and Transplantation Surgery, Wroclaw Medical University, Wroclaw, Poland.
P
P
Szyber
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
A
A
Sas
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
M
M
Klinger
D000328:Adult; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D044022:Receptor, Endothelin A / Q000276:immunology*; D014184:Transplantation, Homologous; D055815:Young Adult
D006680:HLA Antigens; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A