Donor-Specific Antibodies Against HLA, MICA, and GSTT1 in Patients with Allograft Rejection and C4d Deposition in Renal Biopsies

Background. Production of antibodies against donor-specific antigens is one of the central mechanisms of allograft rejection. This antibody-mediated rejection (AMR) is evidenced by the presence of circulating donor-specific antibodies and deposition of complement component C4d on renal endothelium. Although anti-human leukocyte antigen (HLA) antibodies account for a high proportion of AMR, in many cases anti-FILA antibodies cannot be demonstrated. In liver transplant, antibodies against glutathione-S-transferase T1(GSTT1) expressed on the graft may induce an antibody response leading to a severe graft dysfunction. In addition, presence of antibodies against major-histocompatibility-complex class 1 chain-related gene A (MICA) has been associated with it poor graft Survival in kidney transplantation. Methods. Pre- and posttransplantation sera from 19 patients fulfilling the criteria for AMR including C4d deposition in renal biopsies were included. Donor-specific antibodies against HLA-I and -II and MICA were studied using Luminex. Anti-GSTT1 antibodies were analyzed by indirect immunoflouorescence and by an ELISA method. A control group of 39 patients with graft dysfunction negative tor C4d was also included. Results. At the time of the biopsy, 4 (21%) patients had only anti-HLA class I antibodies; 3 (15.8%) had anti-GSTT1, 2 (10.5%) had anti-HLA-class II, and 2 (10.5%) had anti-MICA; four patients had combination of antibodies: HLA1+MICA (n=1), HLA-I+GSTT1 (n=2), and GSTT1 + MICA (n=1). No antibodies were found in 4 (21%) patients. In total, 6 (31.6%) C4d(+) patients had anti-GSTT1 antibodies, whereas, among the 39 C4d-negative patients, only 3 (7.7%) had anti-GSTT1 antibodies (P=0.027). Conclusion. Besides anti-HLA antibodies, donor-specific antibodies against MICA and GSTT1 antigens Could be responsible for the occurrence of antibody-mediated kidney graft rejection.