False-Positive T-Cell Cytotoxicity Crossmatch Results Due to Autoantibodies in Korean Network for Organ Sharing Crossmatch Tests

Abstract

Background: Basic National Institute of Health (NIH) and sensitive antihuman globulin (AHG) methods are widely used for T-cell complement-dependent cytotoxicity crossmatch (XM) tests. Whereas NIH-negative, AHG-positive (NIH-/AHG＋) results are caused by weak antibodies, NIH＋/AHG- results are usually due to autoantibodies. We found that solid organ transplantation candidates with NIH＋/AHG- XM results are repeatedly excluded from allocation of deceased donor organs by the Korean Network for Organ Sharing (KONOS) allocation system. Here, we attempted to demonstrate that these patients do not have donor-specific HLA antibodies (DSAs). Methods: Sera showing NIH＋/AHG- results in the analysis of 1,668 KONOS T-cell XM tests were screened for panel reactive antibody (PRA) using a Luminex test. For screen-positive samples, antibody identification was conducted using a Luminex single antigen assay and the presence or absence of class I DSAs was determined. For positive controls, 42 KONOS XM tests showing probable true-positive (NIH-/AHG＋ or NIH＋/AHG＋) results were reviewed for PRA results based on electronic medical records and the presence or absence of DSAs was determined. Results: NIH＋/AHG- results were observed in 1.3% (21/1,668) of KONOS XM tests analyzed. Most of these (18/21, 85.7%) were negative for PRA or DSAs. All probable true-positive cases were either positive for DSAs (24/42, 57.1%) or had high PRA (mean, 92% [range; 42%∼100%]), complicating accurate identification of antibody specificities. Conclusions: NIH＋/AHG- results are not rare (1.3%) in KONOS XM tests. Most of these results are not due to DSAs, and these patients should not be excluded from organ allocation.