title: The role of immunoglobulin-G subclasses and C1q in de novo HLA-DQ donor-specific antibody kidney transplantation outcomes.
abstract: BACKGROUND
  Anti-HLA-DQ antibodies are the predominant HLA class II donor-specific antibodies (DSAs) after transplantation. Recently, de novo DQ DSA has been associated with worse allograft outcomes. The aim of this study was to determine the further complement-binding characteristics of the most harmful DQ DSA.
  
  
  METHODS
  Single-antigen bead technology was used to screen 284 primary kidney transplant recipients for the presence of posttransplantation DQ DSA. Peak DSA sera of 34 recipients with only de novo DQ DSA and of 20 recipients with de novo DQ plus other DSAs were further analyzed by a modified single-antigen bead assay using immunoglobulin (Ig)-G subclass-specific reporter antibodies and a C1q-binding assay.
  
  
  RESULTS
  Compared with recipients who did not have DSA, those with de novo persistent DQ-only DSA and with de novo DQ plus other DSAs had more acute rejection (AR) episodes (22%, P=0.005; and 36%, P=0.0009), increased risk of allograft loss (hazards ratio, 3.7, P=0.03; and hazards ratio, 11.4, P=0.001), and a lower 5-year allograft survival. De novo DQ-only recipients with AR had more IgG1/IgG3 combination and C1q-binding antibodies (51%, P=0.01; and 63%, P=0.001) than patients with no AR. Furthermore, the presence of C1q-binding de novo DQ DSA was associated with a 30% lower 5-year allograft survival (P=0.003).
  
  
  CONCLUSIONS
  The presence of de novo persistent, complement-binding DQ DSA negatively impacts kidney allograft outcomes. Therefore, early posttransplantation detection, monitoring, and removal of complement-binding DQ might be crucial for improving long-term kidney transplantation outcomes.
authors.affiliation: Terasaki Foundation Laboratory, Los Angeles, CA 90064, USA. cfreitas@terasakilab.org
authors.forename: Maria Cecilia S
authors.initials: MC
authors.lastname: Freitas
authors.forename: Lorita M
authors.initials: LM
authors.lastname: Rebellato
authors.forename: Miyuki
authors.initials: M
authors.lastname: Ozawa
authors.forename: Anh
authors.initials: A
authors.lastname: Nguyen
authors.forename: Nori
authors.initials: N
authors.lastname: Sasaki
authors.forename: Matthew
authors.initials: M
authors.lastname: Everly
authors.forename: Kimberly P
authors.initials: KP
authors.lastname: Briley
authors.forename: Carl E
authors.initials: CE
authors.lastname: Haisch
authors.forename: Paul
authors.initials: P
authors.lastname: Bolin
authors.forename: Karen
authors.initials: K
authors.lastname: Parker
authors.forename: William T
authors.initials: WT
authors.lastname: Kendrick
authors.forename: Scott A
authors.initials: SA
authors.lastname: Kendrick
authors.forename: Robert C
authors.initials: RC
authors.lastname: Harland
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
mesh_terms: D000328:Adult; D000368:Aged; D015922:Complement C1q / Q000276:immunology*; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006683:HLA-DQ Antigens / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000145:classification* / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D006683:HLA-DQ Antigens; D007074:Immunoglobulin G; D007518:Isoantibodies; D015922:Complement C1q