title: Role of Pretransplant Complement-fixing Donor-specific Antibodies Identified by C1q Assay in Kidney Transplantation.
abstract: BACKGROUND
  Kidney transplant recipients who have pretransplant donor-specific human leukocyte antigen (HLA) antibodies have greater risk for developing allograft rejection and allograft loss. However, there is a varied effect of graft injury among patients with pretransplantation donor-specific antibodies (DSA). The difference of complement activating ability may be the reason why some DSA are detrimental to kidney allograft. This study aimed to investigate the association between pretransplantation C1q-binding DSA and clinical outcomes.
  
  
  METHODS
  This retrospective study included 48 pretransplant sera from kidney transplant recipients who had pretransplant DSA with negative complement-dependent cytotoxic (CDC) crossmatches. The IgG DSA testing and C1q testing were performed on a Luminex platform with single antigen bead assay. The clinical outcomes between C1q-positive and C1q-negative groups were compared.
  
  
  RESULTS
  C1q-positive DSA were detected in 12 out of 48 patients (25%). The incidences of antibody-mediated rejection (AMR) were higher among patients with C1q-positive DSA than patients with C1q-negative DSA (66.7% vs 41.7%). Nevertheless, there were no statistically significant associations between C1q-DSA and AMR (odds ratio 2.8, 95% CI 0.68-11.6, P = .13) and between C1q-DSA and graft loss (odds ratio 0.52, 95% CI 0.09-2.89, P = .44). The C1q-positive DSA group had significantly higher IgG DSA MFI than the C1q-negative DSA group (P < .001).
  
  
  CONCLUSIONS
  C1q-binding ability of DSA in pretransplant sera of kidney recipients was not associated with antibody-mediated rejection and graft loss post-transplantation. In contrast with the clinical relevance of C1q testing in the post-transplantation setting, C1q testing in pretransplant sera has limited use for immunological risk assessment.
authors.affiliation: Histocompatibility and Immunogenetics Laboratory, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Electronic address: duangtawan.tha@mahidol.ac.th.
authors.forename: D
authors.initials: D
authors.lastname: Thammanichanond
authors.affiliation: Nephrology Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Wiwattanathum
authors.affiliation: Histocompatibility and Immunogenetics Laboratory, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: T
authors.initials: T
authors.lastname: Mongkolsuk
authors.affiliation: Nephrology Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Kantachuvesiri
authors.affiliation: Immunopathology Laboratory, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Worawichawong
authors.affiliation: Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: S A
authors.initials: SA
authors.lastname: Vallipakorn
authors.affiliation: Histocompatibility and Immunogenetics Laboratory, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Kitpoka
mesh_terms: D000328:Adult; D003167:Complement Activation; D015922:Complement C1q / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000276:immunology; D006680:HLA Antigens / Q000097:blood / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D057234:Preoperative Period; D012189:Retrospective Studies; D018570:Risk Assessment; D014019:Tissue Donors; D066027:Transplant Recipients
chemical_list: D006680:HLA Antigens; D007074:Immunoglobulin G; D015922:Complement C1q