Allografting patients with human leukocyte antigens (HLA) which are recognized by preformed antibodies constitutes the main cause for hyper-acute or acute rejections. In order to select recipients without these donor-specific antibodies, the complement-dependent cytotoxicity crossmatch (CDC-CM) assay was developed as a standard procedure about forty years ago. The negative outcome of pretransplant crossmatching represents the most important requirement for a successful kidney graft survival. The artificially positive outcomes of CDC-based crossmatches due to the underlying disease Systemic Lupus Erythematosus (SLE), however, may lead to the unjustified refusal of adequate kidney grafts. Two prospective female recipients destined for a living as well as for a cadaver kidney donation, respectively, exhibited positive CDC-based crossmatch outcomes although for both patients no historical immunizing events were known. Furthermore, solid phase-based screening or antibody differentiation analyses never led to positive results. Immediate reruns of the CDC-based crossmatch assays using the alternative antibody monitoring system (AMS-)crossmatch ELISA resulted in unequivocally negative outcomes. Consequently both transplantations were performed without any immunological complications for the hitherto follow-up time of 25 and 28 months, respectively. We here show two case reports demonstrating an alternative methodical approach to circumvent CDC-based artefacts and point to the urgent need to substitute the CDC-based crossmatch procedure at least for special groups of patients. 1. Introduction According to the transplantation guidelines of most countries or supranational societies supervising the allocation of kidneys (e.g., Eurotransplant Foundation) the existence of donor-specific anti-HLA antibodies (DSA) is regarded as a contraindication for grafting. This holds true for cadaver as well as for living kidney donations thus requiring the procedure of pretransplant crossmatching. Especially patients characterized by a previous exposure to nonself HLA antigens have (i) to be screened very carefully for anti-HLA antibodies and (ii) to carefully undergo the procedure of crossmatching with a potential kidney donor since DSA have been known for years to be associated with hyperacute or acute rejection episodes up to complete graft loss. To exclude DSA the complement-dependent cytotoxicity crossmatch assay (CDC-CM) was established in the late sixties of the last century as a standard technique by incubating the donors’ lymphocytes with sera of the potential recipients
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