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. 2021 Jan 22;10(3):422.
doi: 10.3390/jcm10030422.

Endothelin A Receptors Expressed in Glomeruli of Renal Transplant Patients May Be Associated with Antibody-Mediated Rejection

Affiliations

Endothelin A Receptors Expressed in Glomeruli of Renal Transplant Patients May Be Associated with Antibody-Mediated Rejection

Katarzyna Nowańska et al. J Clin Med. .

Abstract

Background: Non-human leukocyte antigen (HLA) anti-endothelin A receptor antibodies are presented as being potentially important, but the expression of the endothelin A receptor in glomeruli (ETA receptor (g+)) has not yet been described. We decided to evaluate the presence and relevance of the ETA receptor in for-cause renal transplant biopsies. The aim of our study was to evaluate the immunoreactivity of the ETA receptor and its significance in patients who underwent a renal transplant biopsy due to the deterioration of transplant function, with detailed characterization of staining in glomeruli.

Methods: The immunohistochemical expression of ETA receptor (ETAR) was analyzed in renal transplant biopsies. Microscopic evaluation was performed on paraffin sections in glomeruli. The analysis was performed using a two-step scale (0: lack of ETAR expression; 1: the presence of ETAR expression-mild to moderate immunoreactivity).

Results: We analyzed 149 patients who underwent renal allograft biopsy after renal transplantation. Positive staining of ETA receptors in glomeruli (ETA receptor (g+)) was noticed in 13/149 (8.7%) patients. Five of these 13 (38.5%) patients with ETA receptor (g+) developed antibody-mediated rejection (AMR), while 13 of the remaining 136 (9.5%) ETA receptor (g-) patients developed AMR (p = 0.0022). Graft loss was noticed in all but one ETA receptor (g+) patient with AMR (4/5; 80%), but only in 2/13 (15%) ETA receptor (g-) patients with AMR (p = 0.009) during the first year after biopsy.

Conclusions: The expression of endothelin A receptors in glomeruli seems to be a potentially important feature in the diagnosis of damage during antibody-mediated rejection. It may help to identify patients at a higher risk of allograft rejection and injury.

Keywords: allograft injury; antibody-mediated rejection; endothelin A receptors; non-HLA antibodies.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Lack of endothelin A receptor (ETAR) expression in the tubular epithelium, glomeruli, and interstitium (200×, hematoxylin). (B) Mild to moderate expression of ETAR in glomeruli with mild to moderate reactivity in the tubular epithelium. Note the focal enhanced immunoreactivity of ETAR in the kidney interstitium (200×, hematoxylin). (C) Mild to moderate immunoreactivity in a glomerulus with high ETAR expression in the tubular epithelium (200×, hematoxylin).

References

    1. Terasaki P.I. A personal perspective: 100-year history of the humoral theory of transplantation. Transplant. 2012;93:751–756. doi: 10.1097/TP.0b013e3182483713. - DOI - PubMed
    1. Terasaki P.I., Cai J. Humoral theory of transplantation: Further evidence. Curr. Opin. Immunol. 2005;17:541–545. doi: 10.1016/j.coi.2005.07.018. - DOI - PubMed
    1. Sellares J., de Freitas D.G., Mengel M., Reeve J., Einecke G., Sis B., Hidalgo L.G., Famulski K., Matas A., Halloran P.F. Understanding the causes of kidney transplant failure: The dominant role of antibody-mediated rejection and nonadherence. Am. J. Transplant. 2012;12:388–399. doi: 10.1111/j.1600-6143.2011.03840.x. - DOI - PubMed
    1. Tait B.D., Susal C., Gebel H.M., Nickerson P.W., Zachary A.A., Claas F.H., Reed E.F., Bray R.A., Campbell P., Chapman J.R., et al. Consensus guidelines on the testing and clinical management issues associated with HLA and Non-HLA antibodies in transplantation. Transplantation. 2013;95:19–47. doi: 10.1097/TP.0b013e31827a19cc. - DOI - PubMed
    1. Banasik M., Boratynska M., Nowakowska B., Halon A., Koscielska-Kasprzak K., Drulis-Fajdasz D., Weyde W., Patrzałek D., Klinger M. Variability in donor-specific alloantibody production after transplantation. Transplant. Proc. 2007;39:2715–2717. doi: 10.1016/j.transproceed.2007.08.054. - DOI - PubMed

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