1.2000
#34-OR
PREDICTING CROSSMATCH OUTCOME IN HIGH PRA RENAL TRANSPLANT PATIENTS: TRIPLET AMINO ACID MATCHING VS. SINGLE-ANTIGEN ANTIBODY SCREENING.
Paul Warner, PhD, CHS (ABHI), Karen Nelson, PhD, Dip (ABHI) and Danny Youngs, CHS (ABHI). Seattle WA, USA, Puget Sound Blood Center, Immunogenetics.
Several strategies to identify acceptable or unacceptable mismatched antigens in highly sensitized transplant patients have recently emerged. One approach is to identify mismatched triplet amino acid (MMTrp) epitopes in silico, based upon patient HLA type (HLAMatchmaker). Another method utilizes single HLA bound to microparticles to assay patient sera for the presence of specific HLA antibody (One Lambda FlowPRA Specific beads [FB]). Here, we compare these two methods.
First, we identified 73 highly sensitized renal transplant candidates (Cl. I PRA > 80%), and compared FB results to antigens identified as 0-5 MMTrp. The frequency of antibodies specific for MMTrp antigens correlated to the level of MMTrps. Several antibody specificities detected by FB were directed against 0-MMTrp antigens (9/45 HLA-A, 30/138 HLA-B). To ascertain relevance to crossmatch outcome, we retrospectively identified 23 of these patients that had been crossmatched by T-cell AHG-CDC against donors whose Cl. I HLA were mismatched by 0-2 MMTrp. In 46 crossmatches, 17/21 positive crossmatches correlated to antibody specificities detected by FB. Differential method sensitivity was implicated in 10 negative AHG-CDC crossmatches that were predicted to be positive by FB. We then performed a prospective study in which patient sera with antibodies specific for 0-MMTrp antigens were crossmatched by flow cytometry with cells mismatched only for the corresponding 0-MMTrp antigen. In 10 crossmatches, 7 were positive. In conclusion, highly sensitized patients are unlikely to make antibodies against antigens that are closely related to autologous HLA, but if such antibodies are detected by FB methods, they are relevant to crossmatch outcome.