HLA-matched donors are being used with increasing frequency for transfusion of platelets or other blood products, for bone marrow transplants and for kidney transplants. However, the exquisite polymorphism of the HLA system makes it difficult, and sometimes impossible, to find perfectly matched donors for a particular patient. Since some HLA types are crossreactive, that is, 2 or more antigens share common determinants, that property is being used to select additional donors who mismatch selectively for crossreactive antigens. While it is hoped that a patient having a given HLA antigen will not make antibodies to a crossreactive one, there is some evidence that, in fact, occurs. The objective of this proposal is to build, experimentally, the data base that will allow to select donors based on poor HLA immunogenicity. This research will utilize the analytical capabilities of flow cytometry as a technique to detect and quantitate antibodies to lymphocytes and platelets with a high degree of sensitivity. The experimental design contemplates testing sera from broadly sensitized patients against cells from donors who are HLA identical or mismatched for crossreactive antigens, studying as many combinations as donors are available for that patient. The HLA-matched donors will be selected from our 5,000 HLA-typed donor file using the same algorithms utilized to find HLA-matched platelet donors. In addition, the in vivo immunogenicity of HLA-matched platelet transfusions will be studied by monitoring the humoral response elicited to the lymphocytes and platelets of the matched donor. Analysis of Blood Bank data in the pertinent patient population indicates that the number of patients available for these in vivo studies will be sufficient for statistically valid conclusions. We expect these results will clarify the impact of the HLA polymorphism in HLA sensitization create more rational basis to overcome its untoward effects.
