Clinical relevance of pretransplant anti-HLA donor-specific antibodies: does C1q-fixation matter?

Transpl Immunol. 2013 Dec;29(1-4):28-33. doi: 10.1016/j.trim.2013.07.002. Epub 2013 Jul 29.

Abstract

Anti-HLA donor-specific antibodies (DSA) identified by single antigen bead array (SAB) are questioned for their excess in sensitivity and lack of event prediction after transplantation.

Population and methods: We retrospectively evaluated specific types of preformed DSA (class I, class II or C1q-fixing) and their impact on graft survival. Kidney transplantations performed across negative CDC-crossmatch were included (n=355). Anti-HLA antibodies were tested using SAB to identify DSA and their capacity to fix C1q.

Results: Twenty-eight patients with pretransplant DSA(+) with MFI>2000 were selected to assess C1q fixation. DSA were C1q+ in 15 patients and C1q- in 13, without significant differences in demographics, acute rejection, graft loss or renal function. The maximum MFI of DSA in patients with C1q-fixing DSA was significantly higher (p=0.008). Patients with DSA class-I suffered more antibody-mediated rejection (AMR) and had worse graft survival than class-II. The capacity of DSA I to fix C1q did not correlate with rejection, graft function or graft loss.

Conclusions: C1q testing in pretransplant sera with DSA was unable to predict acute antibody-mediated rejection or early graft loss, but the presence of DSA class I compared to DSA only class II did. Despite non-fixing complement in vitro, pretransplant C1q-negative DSA I can mediate rejection and graft loss.

Keywords: AMR; Antibody-mediated rejection; CDC; Complement; Complement-dependent cytotoxic; DSA; Donor-specific antibodies; Donor-specific antibody; HLA antibody; IQR; Interquartilic range; Kidney transplantation; MFI; Mean fluorescence index; SAB; Single antigen bead array.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Allografts
  • Complement Activation*
  • Complement C1q / immunology
  • Complement C1q / metabolism*
  • Female
  • Graft Rejection / blood*
  • Graft Rejection / etiology
  • Graft Rejection / immunology
  • Graft Survival*
  • HLA Antigens / blood*
  • HLA Antigens / immunology
  • Humans
  • Isoantibodies / blood*
  • Isoantibodies / immunology
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Tissue Donors*

Substances

  • HLA Antigens
  • Isoantibodies
  • Complement C1q