INDUCTION OF ANTIIDIOTYPIC ANTIBODIES TO DONOR HLA-A2 FOLLOWING BLOOD TRANSFUSIONS IN A HIGHLY SENSITIZED HLA-A2+ RECIPIENT

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Abstract
A patient (HLA-A2,3; B35,60) with end-stage renal disease and a high level of pretransfusion (to) anti-HLA cytotoxic antibodies (60% positive to a random panel), but lacking cytotoxic antibodies against her HLA haploidentical sister (HLA-A2,3; B35,44), received 3 donor-specific transfusions (DST) from the latter: 200 cc fresh whole blood at biweekly intervals, while being treated with azathioprine (AZA, 1 mg/kg/day). Her serum remained negative for antidonor antibodies both by standard cytotoxicity assay and by immunofluorescence flow cytometry after DST + AZA treatment, and she experienced no acute rejection episodes following donor kidney transplantation. Microcytotoxicity inhibition tests were performed using standard HLA-typing sera as a source of Ab-1, and pre- and posttransfusion sera were added to serial dilutions of Ab-1 to test for the presence of Ab-2 (antiidiotype) to donor HLA class I specificities. Although both pre- and posttransfusion sera inhibited cytotoxicity toward HLA-A2 antigens expressed on recipient target cells, only posttransfusion serum was found to inhibit cytotoxicity against the HLA-A2 antigens expressed on donor target cells. Absorption of soluble HLA class I antigens present in pre- or posttransfusion sera removed the inhibition of cytotoxicity toward recipient HLA-A2 but did not affect the inhibition of cytotoxicity toward donor HLA-A2 by posttransfusion sera. The F(ab'')2 fragment of the IgG fraction of posttransfusion sera contained the inhibitory activity, suggesting induction of Ab-2 toward idiotypes specific for donor HLA-A2 antigens encoded on the unshared haplotype.

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