Algorithms for the determination of unacceptable HLA antigen mismatches in kidney transplant recipients

AbstractOne of the major tasks of human leukocyte antigen (HLA) laboratories is thepretransplant determination of unacceptable HLA antigen mismatches (UAM) inorgan transplant recipients. HLA antigen specificities are determined against which thepatient has circulating alloantibodies that are expected to harm the transplanted organ.Using the information on UAM, negative crossmatch (XM) prediction or ‘virtualXM’ is possible when a potential donor’s complete HLA typing is available. Beforethe introduction of solid-phase antibody detection assays, UAM were determinedusing the complement-dependent cytotoxicity methodology. After the introduction ofthe single antigen bead technique, however, various UAM determination algorithmshave emerged. In this report, six different laboratories worldwide present how theydetermine UAM in their collective of kidney transplant recipients in the pretransplantphase and proceed thereafter to transplantation.IntroductionThe determination of unacceptable HLA antigen mismatches(UAM) is a critical decision step because with increasing num-ber of forbidden antigen mismatches, the patient’s chance toreceive an organ offer diminishes dramatically. Especially inhighly sensitized patients with alloantibody reactivity againstmany different human leukocyte antigen (HLA) alleles, thismay result in extremely prolonged waiting times associatedwith death of a significant proportion of patients on the wait-ing list. Conversely, unrecognized UAM frequently leads toinferior graft survival and futile organ shipments due to apositive crossmatch (XM) in the recipient center.It is presently unclear which antibody test at what sensitiv-ity level is most appropriate for the determination of UAM.While pretransplant donor-specific HLA antibodies (DSA)detected by complement-dependent cytotoxicity (CDC) areconsidered a contraindication for transplantation (Tx), DSAdetected by other more sensitive assays represent varyingdegrees of risk (1). The single antigen bead assay on theLuminex platform (SAB) with its high resolution allows theprecise determination of HLA antibody specificities whichwas, especially in highly sensitized patients, not possibleearlier. Many laboratories no longer use CDC assays toscreen for HLA antibodies and depend on SAB alone todecide whether an antigen mismatch is unacceptable or not.During the 26th EFI Annual Meeting, Liverpool, 2012,six laboratories across the world with affiliation to differentorgan sharing organizations were asked to present their UAMdetermination algorithms. The objective of this effort wasto obtain a snapshot of the current situation and to gainknowledge from each other.The Leiden approachThe histocompatibility laboratory in Leiden serves the renaltransplant center both in Leiden and in Rotterdam. Thecombined kidney waiting list of these centers comprises 250active patients. In 2011 and 2012, 182 and 186 deceased-and 187 and 200 living-donor kidney Tx were performed,respectively. As a Eurotransplant center, since 1996 themain allocation criteria for kidneys from deceased donors