title: Significance of C1q-fixing donor-specific antibodies after kidney transplantation.
abstract: OBJECTIVE
  De novo donor-specific HLA antibodies (DSA) are associated with allograft rejection and allograft loss. However, not all DSA are equally detrimental to allograft function. The ability to activate complement may be an important factor differentiating clinically relevant DSA from nonrelevant DSA. The C1q assay detects a subset of HLA antibodies that can fix complement. This study aimed to investigate the correlation between C1q-fixing de novo DSA (dnDSA) and clinical outcomes posttransplant.
  
  
  METHODS
  This retrospective study included 193 sera from kidney transplant recipients who underwent posttransplant DSA testing and/or kidney biopsy for clinical causes. Thirty-five of the 193 (18.1%) had immunoglobulin G DSA. Seventeen of the 35 patients were excluded owing to the presence of pretransplant HLA antibodies. We then analyzed C1q DSA at the time of biopsy in 18 recipients who developed dnDSA. The clinical outcomes of patients with C1q-positive DSA and C1q-negative DSA were compared.
  
  
  RESULTS
  C1q-positive DSA were detected in 10 of 18 patients (55.6%). The incidences of transplant glomerulopathy were significantly higher among patients with C1q-positive DSA than patients with C1q-negative DSA (80% vs 0%; P = .001). Although patients with C1q-positive DSA experienced more chronic antibody-mediated rejection and graft loss (80% vs 37.5% [P = .145]; 60% vs 25% [P = .188]), the differences were not significant. The receiver operating characteristic curve analysis showed that the C1q assay was an excellent predictor of transplant glomerulopathy with area under the curve of 0.9 (95% CI, 0.769-1.000).
  
  
  CONCLUSIONS
  The presence of C1q-positive dnDSA was associated with an increased risk of transplant glomerulopathy. The C1q assay is potentially a powerful method for identifying patients at risk for transplant glomerulopathy.
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: 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: Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Rattanasiri
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: Vascular and Transplantation Surgery, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Jirasiritham
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; D015922:Complement C1q / Q000276:immunology*; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007074:Immunoglobulin G; D015922:Complement C1q