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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.
MedLine Citation:
PMID:  22127594     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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:
G Schlaf; C Mauz-Körholz; U Ott; S Leike; W Altermann
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Histology and histopathology     Volume:  27     ISSN:  1699-5848     ISO Abbreviation:  Histol. Histopathol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-11-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8609357     Medline TA:  Histol Histopathol     Country:  Spain    
Other Details:
Languages:  eng     Pagination:  31-8     Citation Subset:  IM    
Affiliation:
Tissue Typing Laboratory, University Hospital Halle, Germany. gerald.schlaf@medizin.uni-halle.de.
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