Flow cytometry crossmatching to investigate kidney-biopsy-proven, antibody-mediated rejection in patients who develop de novo donor-specific antibodies

Transpl Immunol. 2020 Aug:61:101303. doi: 10.1016/j.trim.2020.101303. Epub 2020 May 5.

Abstract

Introduction: The appearance of de novo donor-specific anti-human leukocyte antigen antibodies (dnDSAs) after kidney transplantation is independently associated with poor long-term allograft outcomes. The objective of the present study was to evaluate the predictive value of a flow cytometry crossmatching (FC-XM) assay after the appearance of dnDSAs related to antibody-mediated allograft rejection (ABMR) after kidney transplantation.

Materials and methods: A total of 89 recipients with dnDSAs after transplantation were included. The crossmatching results were compared with the dnDSA profile (the mean fluorescence intensity (MFI), the complement-binding activity, and the IgG subclass profile) and the biopsy's morphological features.

Results: Of the 89 patients, 59 (66%) were positive in an FC-XM assay, 17 (19%) had complement-binding DSAs, 55 (62%) were positive for IgG1 and/or IgG3 in a solid phase assay, and 45 (51%) had morphological biopsy features linked to ABMR.

Conclusion: An FC-XM assay was unable to discriminate between cases with or without ABMR on biopsy findings; it had a low positive predictive value (<70%) and a low negative positive predictive value (<42.9%), taking into account the sensitivity of our assay (limit of detection: DSAs with an MFI >3000). In this context, the height of the MFI of the dnDSAs might be enough for a high positive predictive value for ABMR and additional testing for complement binding activity can remain optional.

Keywords: Antibody mediated rejection; Cross-matching; Crossmatch, crossmatching, HLA; Kidney transplant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Blood Grouping and Crossmatching / methods*
  • Female
  • Flow Cytometry
  • Graft Rejection / diagnosis
  • Graft Rejection / immunology*
  • HLA Antigens / immunology
  • Histocompatibility Testing
  • Humans
  • Isoantibodies / metabolism
  • Kidney / pathology*
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Transplantation, Homologous
  • Young Adult

Substances

  • HLA Antigens
  • Isoantibodies