Induction of antiidiotypic antibodies to donor HLA-A2 following blood transfusions in a highly sensitized HLA-A2+ recipient.
A patient (HLA-A2,3; B35,60) with end-stage renal disease and a high level of pretransfusion (t0) 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.
Burlingham
W J
WJ
Department of Surgery, University of Wisconsin Hospital, Madison 53792.
Pan
M H
MH
Mason
B
B
Ceman
S
S
Sollinger
H W
HW
D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis* / Q000502:physiology; D000918:Antibody Specificity; D000961:Antilymphocyte Serum / Q000096:biosynthesis* / Q000502:physiology; D001379:Azathioprine / Q000627:therapeutic use; D001667:Binding, Competitive; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D015789:HLA-A2 Antigen; D015235:HLA-B Antigens; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D016030:Kidney Transplantation; D010641:Phenotype; D014019:Tissue Donors; D065227:Transfusion Reaction
D000888:Antibodies, Anti-Idiotypic; D000961:Antilymphocyte Serum; D006680:HLA Antigens; D015789:HLA-A2 Antigen; D015235:HLA-B Antigens; D007106:Immune Sera; D007130:Immunoglobulin Idiotypes; D001379:Azathioprine