Clinical Importance of type 1 Angiotensin II Receptor (ATR1) y Anti-endotelin-1 type A (ETAR) Antibodies plus HLA Antibodies in Kidney Transplantation.
Jaouad El kaaoui El band1, Pedro Martinez-Garcia1, Manuela Lopez1, Gema Gonzalez-Martinez1, Rafael Alfaro1, Jose Antonio Galian1, Maria Rosa Moya-Quiles1, Santiago Llorente2, Manuel Muro1.
1Immunology, Clinical University Hospital "Virgen de la Arrixaca", Murcia, Spain; 2Nephrology, Clinical University Hospital "Virgen de la Arrixaca", Murcia, Spain
Introduction: Specific non-HLA antibodies directed to the angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) of the vascular cells can be responsible of antibody mediated rejection in the absence of the donor´s specific anti-HLA antibodies.
Objectives: To determine the presence of non-HLA antibodies in both the pre-trans-plant and post-transplant sera, its participation in acute humoral rejection, and its relation with respect to donor´s specific anti-HLA antibodies.
Patients and Methods: The presence of anti-ETAR and anti-AT1R antibodies was evaluated in stored serum samples of 125 consecutive recipients in kidney pre-transplant and during the first 12 months post-transplantation. The study of these antibodies was evaluated by ELISA technique. Levels of concentration larger than 10 U/ml of anti-ETAR and anti-AT1R were considered as positive. The determination of the presence of HLA antibodies, included in this study, was routinely performed by Luminex technology.
Results: Levels of non-HLA antibodies (anti-AT1R and/or anti-ETAR) were positive in 30 (24.0%) out of 125 of the studied patients. The performed tests were positive in 28 (22.4%) patients with anti-AT1R antibodies and 12 (9.8%) with anti-ETAR from the total of 125 patients, 10 of them had presence of both non-HLA antibodies. In the pre-trans-plant sera, the average level of positive non-HLA antibodies was found to be equal to 16.12±10.61 U/ml anti-ETAR and 15.39 ±8.47 U/ml anti-AT1R, while the latter was equal to 17.61±9.10 U/ml anti-ETAR and 15.10±6.47 U/ml anti-AT1R in post-transplant sera. Graft loss mediated by acute humoral rejection during the first year post-trans-plantation was detected in 8 patients with positive result in non-HLA antibodies, alt-hough only 4 showed donor´s specific anti-HLA antibodies. Chronic humoral rejection was found in 1 patient, and acute cellular rejection in another patient. The presence of C4d was detected in 2 of the 30 mentioned positive patients.
Conclusions: A high correlation between the levels of non-HLA antibodies and reduced kidney function during the first 12 months after transplantation was found, especially in 7 presence of donor´s specific anti-HLA antibodies. Anti-AT1R and anti-ETAR antibodies can be useful to evaluate the risk of allograft loss.
