ASSAYS TO PREDICT ALLOGRAFT REJECTION

N. Reinsmoen¹, C. Lai¹, H. Heidecke², K. Cao³, G. Ong³, M. Naim³, Q. Wang³, J. Mirocha³, A. Vo³, S. Jordan³, D. Dragun^2
1, Cedars-Sinai Medical Center, Los Angeles/CA/UNITED STATES OF AMERICA, ², Charite Medical School, Berlin/GERMANY, ³, Cedars-Sinai Medical Center, Los Angeles/UNITED STATES OF AMERICA

Body: Introduction: AT₁R mediates most physiologic and pathophysiologic actions of its endogenous ligand, antiogensin II with over activity leading to vascular remodeling and hypertension. Antibodies to the polymorphic AT₁R exert their effect on endothelial cells and smooth muscle cells by activation of the ERK1/2 cascade, increasing DNA binding of NF-KB, and can also fix complement. The aim of our study was to determine the impact of antibody to AT₁R on clinical outcomes including C4d+ AMR in patients whose pretransplant (pretx) sera contained no DHSA. Methods: Pretransplant sera and sera obtained at the time of acute rejection (AR) were tested by Luminex-based single antigen bead assays to determine DHSA. Antibodies to Major Histocompatibility class I related gene A (MICA) were also assayed by Luminex-based methods. Sera from 70 recipients were determined to have no DHSA and no donor specific MICA antibodies pretransplant and at the time of AR. These 70 sera were tested for AT₁R by a cell-based ELISA method using a cutoff of 17 units to distinguish high from low binding. Results: Sera from 49% (34/70) recips showed high binding to AT₁R. Of the 70 recipients, 16 were diagnosed with acute rejection (AR) including 6 with C4d+ AMR and 10 with C4d- cellular AR. High binding AT₁R antibodies were identified for 5 of 6 in the AMR+ group and 1 of 10 in the CMR+ group (p=0.008). Sera from the 6 recipients with AMR did not contain donor specific antibody to MICA. At no time pre or posttx were DHSA detected for the AMR+ group. Of the 34 with high AT₁R Antibody, the cause of renal failure for 24 recipients was hypertension (HTN) including 5 with posttx malignant HTN and 11 with concomitant autoimmune diseases (AID, i.e., lupus, diabetes, IgAN), 4 had autoimmune diseases alone and 6 had unknown or other diagnoses. Conclusions: A strong association was observed between the presence of high binding to AT1R and AMR in recipients whose sera contained no antibody to donor HLA or MICA antigens (P=0.008). These results provide insight into the antibody mediated rejection process in the absence of DHSA. Assessing the AT1R antibody status along with the DHSA provides additional information to determine the immunological risk for recipients and can provide the opportunity for clinical intervention.

Disclosure: All authors have declared no conflicts of interest.