title: Downregulation of the anti-HLA alloimmune response by variable region-reactive (anti-idiotypic) antibodies in leukemic patients transfused with platelet concentrates.
abstract: Approximately 30% to 40% of patients with acute leukemia receiving repeated pooled random-donor platelet transfusions develop anti-HLA alloantibodies. Over time, however, serum anti-HLA concentrations decrease in approximately 50% of these patients, despite continued exposure to platelet and/or red blood cell transfusions. Using an enzyme-linked immunosorbent assay to measure serum Igs, the present study demonstrates that the sera of 67% of 82 transfused patients exhibiting a decrease in anti-HLA contain antibodies (anti-idiotypes) that react with the variable (V) region of anti-HLA antibodies. Anti-HLA binding to platelet membranes could be inhibited by these serum antibodies in 36% of the patients, indicating they had paratope-related reactivity. Protein G sepharose absorption showed that the anti-HLA V region-reactive antibodies were IgG. Of the 43 patients who had a decrease in anti-HLA levels, that were 16 whose anti-HLA decreased to undetectable levels; 7 (44%) developed anti-idiotypic antibodies that could specifically inhibit their own previously anti-HLA-positive serum. In contrast, antibodies with reactivity to the V region of anti-HLA antibodies (anti-idiotypes) were not demonstrable in patients who developed anti-HLA that did not decrease or disappear. The findings suggest that the development of anti-HLA V region-reactive antibodies (anti-idiotypic antibodies) correlates with a decrease in anti-HLA antibody formation in patients multiply transfused with platelet concentrates. The observations indicate that anti-idiotypic antibodies may downregulate alloimmune responses in patients undergoing repeated allostimulation during platelet transfusion therapy.
authors.affiliation: Division of Hematology, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Atlas
authors.forename: J
authors.initials: J
authors.lastname: Freedman
authors.forename: V
authors.initials: V
authors.lastname: Blanchette
authors.forename: M D
authors.initials: MD
authors.lastname: Kazatchkine
authors.forename: J W
authors.initials: JW
authors.lastname: Semple
mesh_terms: D000208:Acute Disease; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D016913:Blood Component Transfusion; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000097:blood*; D007518:Isoantibodies / Q000097:blood*; D007938:Leukemia / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D008297:Male
chemical_list: D000888:Antibodies, Anti-Idiotypic; D006680:HLA Antigens; D007140:Immunoglobulin Fab Fragments; D007135:Immunoglobulin Variable Region; D007518:Isoantibodies