HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Review

General insufficiency of the classical CDC-based crossmatch to detect donor-specific anti-HLA antibodies leading to invalid results under recipients’ medical treatment or underlying diseases

Gerald Schlaf1, Christine Mauz-Körholz2, Undine Ott3, Steffen Leike4 and Wolfgang Altermann1

1Tissue Typing Laboratory and 2Department of Pediatrics, University Hospital Halle, Germany, 3Department of Nephrology, University Hospital Jena, Germany and 4Clinic of Urology, University Hospital Dresden, Germany.

Offprint requests to: Gerald Schlaf and Wolfgang Altermann, Tissue Typing Laboratory (GHATT), University Hospital Halle, Magdeburger Strasse 16, 06112 Halle Germany. e-mail: gerald.schlaf@medizin.uni-halle.de


Summary. Antibodies directed against HLA antigens of a given donor represent the most prominent cause for hyper-acute and acute rejections. In order to select recipients without donor-specific antibodies the complement-dependent cytotoxicity (CDC-) crossmatch as the standard procedure was established. As a functional assay it strongly depends on the availability of isolated donor lymphocytes and in particular on their vitality. However, due to several diseases or pharmacological treatment of a given recipient unexpected “false-positive” results of the CDC-crossmatch may arise. We here present three groups of patients which demonstrate the limits of the conventional crossmatch. 1) Kidney recipients before living donations exhibited positive CDC-reactions due to their conditioning using the therapeutical anti-CD20 mAb Rituximab (n=7), routinely used to deplete B-cells, or the anti-CD25 mAb Basiliximab (n=2) to inhibit the proliferation of activated T-cells. 2) Recipients suffering from various leukaemias (n=5) exhibited “positive” CDC-crossmatches using PBL of the donors, although formerly these patients had never shown anti-HLA antibodies. Instead of donor-specific allo-antibodies, cytostatic agents such as 6-Mercaptopurine led to an unspecific cell death. 3) Patients projected for post mortem or living kidney donations (n=44) exhibited “positive” CDC-crossmatch results which were not in accordance with their former antibody status and, partially, with high degrees of HLA-matching. These implausible results were due to underlying auto-immune diseases, mainly of the systemic Immune Complex Type III such as Lupus Erythematosus, mainly leading to false-positive B-cell crossmatches by immune complexes binding to Fcγ-receptors. In all these 58 cases the alternatively performed ELISA-based “Antibody Monitoring System” (AMS-) crossmatch assay was not artifically affected, suggesting that this assay may be comprehensively established at least for the cases described
. Histol Histopathol 27, 31-38 (2012)

Key words: Allograft, Crossmatch, Donor-specific Antibodies, Human leukocyte antigen, Rejection

DOI: 10.14670/HH-27.31