Evaluation of Antibodies Directed Against Two GPCRs, Anti-AT1R and Anti-ETAR, on Kidney Transplant Outcome

The role of an alloimmune response against non-self-antigens is established in organ transplantation. HLA incompatibilities are mainly responsible for this recognition between donor and recipient, but they may also be involved in the reactivity against other alloantigens expressed on the allograft resulting from an autoimmune response developed against selfantigens.

Our study aimed to determine the presence of non-anti-HLA antibodies (anti-AT1R and anti-ETAR) in sera from patients with end-stage renal disease, who underwent kidney transplantation in pre- and post-transplantation samples to study their influence on the development and evolution of acute humoral rejections and DSAs.

Antibodies (Abs) against two G protein-coupled receptors (GPCRs), angiotensin II type 1 receptor (AT1R) and endothelin-1 type A receptor (ETAR), have been detected in the sera of transplant recipients, who experience allograft dysfunction, patients with coronary heart disease, marginal hypertension and refractory, vascular lesions, myocardial hypertrophy and chronic inflammatory diseases, such as atherosclerosis or sclerosis.

Kidney graft recipients were monitored for anti-ETAR, -AT1R, and -HLA Abs in pre-and post-transplant evolution, and anti-AT1R and/or -ETAR Abs were detected in 24% of recipients (22.4% with anti-AT1R Abs and 9.8% with anti-ETAR Abs). Due to acute humoral rejection, Graft loss was detected in 6.4% of patients with anti-GPCRs non-HLA Abs, and 3.2% had DSA anti-HLA Abs. In this research, we have described how the function of the anti-GPCRs autoAbs and how these Abs that activate GPCRs could influence graft outcome.

In conclusion, there is a high association of non-HLA anti-GPCRs Abs levels with reduced kidney function after transplantation, especially in the presence of DSA anti-HLA Abs. Although more studies are needed, anti-AT1R and anti-ETAR antibodies may be helpful biomarkers that allow the risk of graft loss to be assessed.