Clinical relevance of preformed C4d-fixing and non-C4d-fixing HLA single antigen reactivity in renal allograft recipients

Transpl Int. 2009 Oct;22(10):982-9. doi: 10.1111/j.1432-2277.2009.00912.x. Epub 2009 Jul 10.


Donor-specific alloantibodies (DSA), especially those fixing complement, may pose a particular immunologic risk to transplant recipients. To assess the clinical impact of C4d- or non-C4d-fixing (IgG) HLA sensitization, pretransplant sera obtained from 338 kidney allograft recipients prescreened by FlowPRA were retrospectively evaluated by Luminex single antigen (SA) testing using a novel fluorescent-labeled anti-C4d reagent for detection of antibody-triggered C4d deposition in addition to IgG binding. Recipients with [IgG]DSA (n = 39) showed a substantially higher rate of C4d positive rejection (33%) than 16 patients with [IgG] non-DSA (0%) or 283 antibody-negative patients (4%, multivariate analysis excluding retransplantation because of high co-linearity: P < 0.0001), and adversely affected 5-year death-censored graft survival (74% vs. 81% and 90%, respectively, multivariate model: P < 0.05). [C4d] DSA (n = 21) and [C4d] non-DSA (n = 25) increased rates of C4d positive rejections to a similar extent (24% and 28% vs. 4% in recipients without C4d-fixing reactivity; multivariate analysis: P <or= 0.002) with a trend towards adverse 5-year graft survival (76% and 76% vs. 90%; P <or= 0.2). In conclusion, Luminex-based characterization of HLA sensitization may be a useful strategy for risk stratification. Possibly as a result of intensified immunosuppression in presensitized recipients, identification of C4d-fixing DSA was not associated with a further increase of rejection and graft loss rates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigen-Antibody Reactions
  • Complement C4b / immunology*
  • Complement Fixation Tests / methods*
  • Female
  • Graft Rejection / immunology
  • HLA Antigens / immunology*
  • Humans
  • Immunoglobulin G / analysis
  • Isoantibodies / immunology
  • Kidney Transplantation / immunology*
  • Male
  • Middle Aged
  • Peptide Fragments / immunology*
  • Tissue Donors
  • Treatment Outcome


  • HLA Antigens
  • Immunoglobulin G
  • Isoantibodies
  • Peptide Fragments
  • Complement C4b
  • complement C4d