The Summarized Assessment of Endothelin A Receptor Expression in Renal Transplant Compartments Associated with Antibody-Mediated Rejection

Abstract

The occurrence of anti-endothelin A receptor antibodies may be useful in diagnosis of transplant damage. We noticed that the presence of the endothelin A receptor (ETA receptor) in biopsy compartments is yet to be defined. We decided therefore to analysed the presence and relevance of the ETA receptor in biopsy to define the cause. Our study aims to evaluate the expression of ETA receptors in renal recipients after a biopsy due to the worsening of transplant function. Methods: The expression of ETA receptors was analyzed in renal transplant biopsies using the immunohistochemical method. The evaluation of ETA receptors was performed on paraffin sections. ETA receptor expression was analyzed in four compartments of renal transplant biopsies: glomeruli; vessels; tubular epithelium; and interstitium. The assessment was presented using a three-step scale (0: lack of expression; 1: mild to moderate immunoreactivity; 2: high expression). The results of each compartment from a single biopsy were summarized and assessed in the context of antibody-mediated rejection (AMR). Results: We analyzed 156 patients who had a renal allograft biopsy after renal transplantation. For each patient, we created a summarized ETA receptor expression score. The summarized ETA receptor expression score analysis showed statistically significant differences in patients with and without AMR. In addition, we noticed that patients with AMR had a significantly higher mean summarized expression of ETA receptor score of 3.28 ± 1.56 compared to patients who had a biopsy for other reasons with a mean summarized ETA receptor expression score of 1.47 ± 1.35 (p < 0.000001). ROC analysis of the ETA receptor expression score for detecting AMR status showed that the most appropriate cut-off for the test of the chosen binary classifier is between 2 and 3 of the summarized ETA receptor expression score. Conclusions: The expression of endothelin A receptors in renal transplant compartments may be associated with antibody-mediated rejection. The positive ETA receptor staining might be a vital feature in the diagnosis of damage in AMR. The summarized ETA receptor expression score seems to be an exciting diagnostic tool in transplant injury assessment.

Significance of Indoleamine 2,3-Dioxygenase Expression in the Immunological Response of Kidney Graft Recipients

“…As mentioned above, it is crucial to pursue new ways of protecting transplanted organs. As a matter of fact, antibody-mediated rejection is the leading player in graft immunological injury and transplant loss, with the massive significance of human leukocyte antigen and the anti-HLA and non-HLA antibodies [ 82 , 83 , 84 , 85 , 86 , 87 , 88 ]. Recent studies have shown that especially the non-HLA antibodies, including anti-ETAR antibodies, should be pursued, as their importance is being revealed [ 89 ].…”

Chronic Active T-Cell Mediated Kidney Rejection as a Clinically Significant Type of Allograft Loss?

“…Moreover, the study has shown a significant association between the AT1R-Ab positivity and positivity for Ab against the endothelin A type 1 receptor (ETAR-Ab) [ 37 ]. Researchers pointed out the need to perform a prospective study regarding high prevalence of AT1R-Ab pre-transplant and its association with TCMR and possible treatment methods in such patients.…”

Association between anti‐endothelial antigen antibodies and allograft rejection in kidney transplantation

“…The endothelium of preglomerular vessels expresses endothelin subtype A receptor (ETAR) 3 and angiotensin II type I receptor (AT1R) at substantially low levels in glomerular endothelial cells 1 . ETAR is highly expressed in the tubular epithelium compared with that in the glomerulus; ETAR positivity in the glomeruli is associated with a high risk of AMR, 4 and the occurrence of graft loss has been reported 5 . This is because the increase in ETAR expression is associated with a reduction in tissue integrity 6 and an increase in autoantibody‐binding capacity 7 .…”