ASSIGNMENT OF HLA-ANTIGENS IN CREGS FACILITATES THE DETECTION OF ACCEPTABLE MISMATCHES IN HIGHLY SENSITIZED PATIENTS

The purpose of this study was to investigate whether in highly sensiti zed patients (HSPs) the acceptable HLA-A and -B mismatches (AMs) can b e predicted on the basis of patients' HLA-phenotype. To this affect, 1 000 historical serum samples obtained from 50 HSPs (PRA > 60%), panel reactive antibodies (PRA) value and the specificity of class I anti-HL A-antibodies were detected by two techniques in parallel: An antihuman globulin augmented cytotoxicity (AHG-CDC) and an Elisa technique. The reafter, class I HLA-antigens of the nonreactive cells in the screenin g panel and class I HLA-antigens of the patients were assigned to CREG s. The AMs for each one of the patients were detected using a separate cell panel, which was prepared in a way to include almost all the HLA -antigens belonging to the CREGs of the patients as well as to those o f the nonreactive cells in the screening panel. It was found that the AMs in HSPs, detected with this protocol were more, compared to those we usually detect using only the HLA-antigens of the nonreactive cells in the screening panel (up to 8 versus 2-5). Both, the definitively d etected AMs, and the HLA-specificities of the nonreactive cells of the screening panel belonged to the same CREGs. These CREGs were equivale nt to the CREGs of class I HLA-phenotypes of each patient. The data pr esented in this paper introduce a new, rapid and easier way for the de tection of AMs in HSPs. According to this proposed protocol, the assig nment of patients' standard class I private HLA-phenotypes in CREGs, n ot only greatly facilitates the detection of AMs, but the detected AMs are also in fact significantly more than those determined by the conv entional methodology. We have also confirmed that the majority of anti bodies induced by HLA alloimmunization are directed against mismatched shared or public group epitopes CREGs. Moreover, we have confirmed th at prospective matching for major CREGs would be feasible on a nationa l level and would not significantly prolong waiting time, which could result in a significant augmentation of the potential donor pool. (C) American Society for Histocompatibility and Immunogenetics, 1998. Publ ished by Elsevier Science Inc.