title: Complement-fixing antibodies against denatured HLA and MICA antigens are associated with antibody mediated rejection.
abstract: BACKGROUND
  We have found antibodies against denatured HLA class I antigens in the serum of allograft recipients which were not significantly associated with graft failure. It is unknown whether transplant recipients also have denatured HLA class II and MICA antibodies. The effects of denatured HLA class I, class II, and MICA antibodies on long-term graft outcome were further investigated based on their ability to fix complement c1q.
  
  
  METHODS
  In this 4-year retrospective cohort study, post-transplant sera from 975 kidney transplant recipients were tested for antibodies against denatured HLA/MICA antigens and these antibodies were further classified based on their ability to fix c1q.
  
  
  RESULTS
  Thirty percent of patients had antibodies against denatured HLA class I, II, or MICA antigens. Among them, 8.5% and 21.5% of all patients had c1q-fixing and non c1q-fixing antibodies respectively. There was no significant difference on graft survival between patients with or without antibodies against denatured HLA/MICA. However, when these antibodies were further classified according to their ability to fix c1q, patients with c1q-fixing antibodies had a significantly lower graft survival rate than patients without antibodies or patients with non c1q-fixing antibodies (p=0.008). In 169 patients who lost renal grafts, 44% of them had c1q-fixing antibodies against denatured HLA/MICA antigens, which was significantly higher than that in patients with functioning renal transplants (25%, p<0.0001). C1q-fixing antibodies were more significantly associated with graft failure caused by AMR (72.73%) or mixed AMR/CMR (61.9%) as compared to failure due to CMR (35.3%) or other causes (39.2%) (p=0.026).
  
  
  CONCLUSIONS
  Transplant recipients had antibodies against denatured HLA class I, II, and MICA antigens. However, only c1q-fixing antibodies were associated with graft failure which was related to antibody mediated rejection.
authors.affiliation: Terasaki Research Institute, Los Angeles, CA, United States. Electronic address: cai@terasakilab.org.
authors.forename: Junchao
authors.initials: J
authors.lastname: Cai
authors.affiliation: Terasaki Research Institute, Los Angeles, CA, United States.
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Charité-Universitätsmedizin Berlin, Center for Tumor Medicine, HLA-Laboratory CampusVirchow-Klinikum, Berlin, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Lachmann
authors.affiliation: Charité-Universitätsmedizin Berlin, Center for Tumor Medicine, HLA-Laboratory CampusVirchow-Klinikum, Berlin, Germany.
authors.forename: Constanze
authors.initials: C
authors.lastname: Schönemann
authors.affiliation: Terasaki Research Institute, Los Angeles, CA, United States.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Everly
authors.affiliation: Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA 90502, United States.
authors.forename: Xin
authors.initials: X
authors.lastname: Qing
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology*; D015922:Complement C1q / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014184:Transplantation, Homologous / Q000379:methods
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D015922:Complement C1q
keywords: Antibody epitope; Antibody-mediated rejection; Denatured antigen; HLA antibody; MICA antibody; Renal transplant; c1q-fixing antibody