Diagnostic Contribution of Donor-Specific Antibody Characteristics to Uncover Late Silent Antibody-Mediated Rejection-Results of a Cross-Sectional Screening Study

Transplantation. 2017 Mar;101(3):631-641. doi: 10.1097/TP.0000000000001195.


Background: Circulating donor-specific antibodies (DSA) detected on bead arrays may not inevitably indicate ongoing antibody-mediated rejection (AMR). Here, we investigated whether detection of complement-fixation, in parallel to IgG mean fluorescence intensity (MFI), allows for improved prediction of AMR.

Methods: Our study included 86 DSA+ kidney transplant recipients subjected to protocol biopsy, who were identified upon cross-sectional antibody screening of 741 recipients with stable graft function at 6 months or longer after transplantation. IgG MFI was analyzed after elimination of prozone effect, and complement-fixation was determined using C1q, C4d, or C3d assays.

Results: Among DSA+ study patients, 44 recipients (51%) had AMR, 24 of them showing C4d-positive rejection. Although DSA number or HLA class specificity were not different, patients with AMR or C4d + AMR showed significantly higher IgG, C1q, and C3d DSA MFI than nonrejecting or C4d-negative patients, respectively. Overall, the predictive value of DSA characteristics was moderate, whereby the highest accuracy was computed for peak IgG MFI (AMR, 0.73; C4d + AMR, 0.71). Combined analysis of antibody characteristics in multivariate models did not improve AMR prediction.

Conclusions: We estimate a 50% prevalence of silent AMR in DSA+ long-term recipients and conclude that assessment of IgG MFI may add predictive accuracy, without an independent diagnostic advantage of detecting complement-fixation.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Area Under Curve
  • Asymptomatic Diseases
  • Biomarkers / blood
  • Biopsy
  • Chi-Square Distribution
  • Complement Fixation Tests
  • Complement System Proteins / analysis
  • Cross-Sectional Studies
  • Female
  • Flow Cytometry*
  • Graft Rejection / blood
  • Graft Rejection / diagnosis*
  • Graft Rejection / epidemiology
  • Graft Rejection / immunology
  • HLA Antigens / immunology*
  • Histocompatibility
  • Humans
  • Immunoglobulin G / blood*
  • Isoantibodies / blood*
  • Kidney / immunology*
  • Kidney / pathology
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Prevalence
  • Prospective Studies
  • ROC Curve
  • Risk Factors
  • Serologic Tests
  • Treatment Outcome


  • Biomarkers
  • HLA Antigens
  • Immunoglobulin G
  • Isoantibodies
  • Complement System Proteins