title: 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.
abstract: 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.
authors: Tissue Typing Laboratory, University Hospital Halle, Germany. gerald.schlaf@medizin.uni-halle.de
authors: G
authors: G
authors: Schlaf
authors: C
authors: C
authors: Mauz-Körholz
authors: U
authors: U
authors: Ott
authors: S
authors: S
authors: Leike
authors: W
authors: W
authors: Altermann
mesh_terms: D001327:Autoimmune Diseases / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005189:False Positive Reactions; D005858:Germany; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000276:immunology; D007938:Leukemia / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D019172:Transplantation Conditioning / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies; D003165:Complement System Proteins