NON-HLA ANTIBODIES AND KIDNEY TRANSPLANTATION: RELEVANCE OF AT1R ANTIBODIES ON GRAFT OUTCOME

Recent studies associated non-HLA antibodies speci?c forAngiotensin II Type-1 Receptor (AT1R) with antibody-mediated rejection (AMR) of kidney allograft. This study analyzed thepresence of AT1R antibodies in kidney transplanted patientsshowing or not showing HLA donor-speci?c antibodies (DSA)production and the correlation of these antibodies with graftoutcome. Sera from 63 kidney transplanted patients were analyzedfor anti-AT1R using a new ELISA assay. Luminex Single Antigentechnique (LSA) was used to analyze de novo DSA production.The capability of detected DSA to ?x C1q was tested by a modi?edLSA assay. Analyzing graft outcome, 50 patients suffered graftfailure (GF)/graft dysfunction (GD) for AMR. Sixteen (26%)patients were DSA-negative/anti-AT1R-negative and did notshow AMR. Twenty-seven (43%) patients were DSA-positive/anti-AT1R-negative; all but one suffered GF/GD and hadC1q-positive DSA. Sixteen (26%) patients were DSA-positive/anti-AT1R-positive; all suffered GF/GD and had C1q-positiveDSA. The remaining 4 (6%) patients were DSA negative/anti-AT1R-positive and suffered GD. The production of DSA onlyand DSA plus anti-AT1R showed signi?cant associations with kid-ney GF/GD (P < 0.0001). At 40 months after antibody appearance,graft survival was 72% for DSA-negative/anti-AT1R-negativepatients, 4% for DSA-positive/anti-AT1R-negative, but allDSA-positive/anti-AT1R-positive patients lost the graft within12 months from antibody appearance. Our study con?rmsthe crucial role of DSA production in kidney transplantationand underlines the synergic effects of anti-AT1R develop-ment on graft outcome. Assessment of anti-AT1R status alongwith de novo DSA development should help in the diagno-sis of AMR and can give the opportunity for speci?c clinicalintervention.