title: Donor-specific antibodies against HLA, MICA, and GSTT1 in patients with allograft rejection and C4d deposition in renal biopsies.
abstract: 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-HLA 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 I chain-related gene A (MICA) has been associated with a 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 immunofluorescence and by an ELISA method. A control group of 39 patients with graft dysfunction negative for 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: HLA-I + 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).
  
  
  CONCLUSIONS
  Besides anti-HLA antibodies, donor-specific antibodies against MICA and GSTT1 antigens could be responsible for the occurrence of antibody-mediated kidney graft rejection.
authors.affiliation: Servicio de Inmunología, Instituto de Biomedicina de Sevilla, Hospitale Universitario Virgen del Rocío/CSIC/Universidad de Sevilla. Sevilla, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Alvarez-Márquez
authors.forename: Isabel
authors.initials: I
authors.lastname: Aguilera
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gentil
authors.forename: José L
authors.initials: JL
authors.lastname: Caro
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bernal
authors.forename: Jorge
authors.initials: J
authors.lastname: Fernández Alonso
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Acevedo
authors.forename: Virginia
authors.initials: V
authors.lastname: Cabello
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Wichmann
authors.forename: Maria F
authors.initials: MF
authors.lastname: Gonzalez-Escribano
authors.forename: Antonio
authors.initials: A
authors.lastname: Núñez-Roldán
mesh_terms: D000906:Antibodies / Q000276:immunology*; D001706:Biopsy; D015935:Complement C4b / Q000276:immunology*; D005982:Glutathione Transferase / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase