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.
Highlights
The study was approved by the Wroclaw Medical University
The presence of ETA receptor expression was assessed in four compartments: glomeruli, Thetubular presence of ETA receptor expressionThe wasanalysis assessedwas in four compartments: glovessels, epithelium, and interstitium
We showed that the summarized expression of ETA receptors in the assessed compartments, i.e., glomeruli, vessels, tubular epithelium, and interstitium, might be related to injury described as antibody-mediated rejection
Summary
Antibody-mediated rejection (AMR) plays a leading role in transplant immunological injury and, transplant loss, but presently, we know that anti-HLA and non-HLA antibodies may be significant [1,2,3,4,5,6,7,8].Endothelin A receptor (ETA receptor) is considered one of the non-HLA antigens, which may be a significant trigger in immunological response and graft loss [9,10,11,12,13].What is more, the importance of non-HLA response was noted in renal recipients and in patients after liver, heart, lung, intestine, and hand transplantation [14,15,16,17,18,19,20].The main function of peptides called endothelins (ETs), produced in the endothelium, is vasoconstriction [21]. Antibody-mediated rejection (AMR) plays a leading role in transplant immunological injury and, transplant loss, but presently, we know that anti-HLA and non-HLA antibodies may be significant [1,2,3,4,5,6,7,8]. Endothelin A receptor (ETA receptor) is considered one of the non-HLA antigens, which may be a significant trigger in immunological response and graft loss [9,10,11,12,13]. The main function of peptides called endothelins (ETs), produced in the endothelium, is vasoconstriction [21]. We noticed that anti-ETAR antibodies in renal transplant recipients might be associated with a worse transplant function compared to patients without such antibodies [10] ETs include peptides described as ET-1, ET-2, ET-3 [22], and ET-1 is a factor that may trigger tubulointerstitial injury and proteinuria when produced in excess by kidneys [23].
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