Reassessment of T Lymphocytes Crossmatches Results Prediction With Luminex Class I Single Antigen Flow Beads Assay

Transplantation. 2017 Mar;101(3):624-630. doi: 10.1097/TP.0000000000001239.

Abstract

Background: In virtual crossmatch (XM) strategies, a correct anticipation of XM results is required for appropriately allocating organs. We reassessed the ability to predict T lymphocyte flow cytometry and complement dependent cytotoxicity XM results with the mean fluorescence intensity (MFI) in Luminex class I single antigen flow beads (SAFB) assay, after correction of complement interference and exclusion of antidenatured HLA antibodies.

Methods: Among 432 XM with T lymphocytes (T-XM), 407 were analyzed after exclusion of antidenatured HLA antibodies. Only ethylenediaminetetraacetic acid-treated serum MFI was considered. Only 1 cellular target HLA antigen for the serum was expressed in 238 cases, 209 and 29 being heterozygous and homozygous for this antigen, respectively. For the remaining 169 cases, at least 2 antigens were recognized. Single antigen flow bead MFI thresholds allowing XM positivity to be predicted were calculated with receiver operating characteristic curves.

Results: T-XM results were tightly associated with SAFB MFI values. Anti-HLA-A and anti-HLA-B antibodies behaved similarly. Prediction and sensitivity SAFB MFI thresholds were determined, respectively, assessing the highest sensitivity/specificity ratio and at least 95% sensitivity for predicting T-XM positivity. Both were slightly lower for HLA-B than for HLA-A, whereas anti-HLA-Cw antibodies induced random XM results. Both thresholds were only slightly diminished for homozygous and for multiple HLA targets, considering the immunodominant, but not the sum, of antibodies MFI.

Conclusions: Antibodies against HLA-A, -B, or -Cw behave differently. A homozygous HLA target does not trigger a twice higher XM positivity. Multiple antibodies are better evaluated through the immunodominant DSA MFI than through the sum of DSA MFI.

MeSH terms

  • Area Under Curve
  • Biomarkers / blood
  • Cytotoxicity Tests, Immunologic
  • Cytotoxicity, Immunologic
  • Flow Cytometry*
  • HLA Antigens / blood
  • HLA Antigens / genetics
  • HLA Antigens / immunology*
  • Heterozygote
  • Histocompatibility Testing / methods*
  • Histocompatibility*
  • Homozygote
  • Humans
  • Isoantibodies / blood*
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / methods*
  • Predictive Value of Tests
  • ROC Curve
  • T-Lymphocytes / immunology*

Substances

  • Biomarkers
  • HLA Antigens
  • Isoantibodies