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JUST HOW COMPLEX ARE THE HLA CLASS I ALLOANTIBODIES IN PATIENTS WITH EXTREMELY HIGH PRA?
Thomas C. Fuller, PhD, Ketra H. Konnick, BS and Anne A. Fuller, BS. Salt Lake City UT, USA, Univ Utah Health Science Center, 841321904, H
I Laboratory.
Introduction: It is generally considered that patients who are very highly sensitized to HLA Class I antigens require a nearly perfect HLA matched donor to attain a negative T cell crossmatch.
Methods: Over 50 highly sensitized transplant patients were screened using indirect antibody binding against Luminex™ bead arrays and/or flow beads. These consisted of 80 different beads that were coupled with individual recombinant HLA-A or B alloantigens (LABScreen®, One Lambda). Recombinant HLA-C alloantigens (16 alleles) were coupled to flow beads (FlowPRA®, One Lambda). Antibody binding was quantified using the Luminex-100™ or BD-FACScan™ instrument, respectively.
Results: 20 highly characterized HLA alloantisera or monoclonals were used to confirm that antigens were indeed present on each bead. With the highly sensitized patients, on average 40% of the 79 alleles were negative indicating that the patients did not have antibody against these specificities; most antibodies were directed to either the A or B locus rather than both. Rarely did any serum react with antigens represented in the patient’s phenotype. In several instances, there was allelic specificity (e.g. B*0702 vs B*0703). Of 17 patients, 29% had no C locus antibodies while 23% had >50% PRA against HLA-C alleles. A number of very high PRA renal transplant patients were successfully transplanted with donors having extreme HLA Class I mismatches using this technology.
Conclusions: High PRA does not imply a plethora of antibodies to all HLA alleles: patients can receive highly mismatched allografts as we had reported over 20 years ago. Facilitated by the single antigen microarray technology, virtual crossmatching of high PRA patients should be feasible.