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Downregulation of the anti-HLA alloimmune response by variable region- reactive (anti-idiotypic) antibodies in leukemic patients transfused with platelet concentrates

Atlas, E. ; Freedman, J. ; Blanchette, V. ; Kazatchkine, M. D. and Semple, J. W. LU (1993) In Blood 81(2). p.538-542
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-... (More)

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, there 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.

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author
; ; ; and
publishing date
type
Contribution to journal
publication status
published
in
Blood
volume
81
issue
2
pages
538 - 542
publisher
American Society of Hematology
external identifiers
  • scopus:0027454992
  • pmid:8422470
ISSN
0006-4971
DOI
10.1182/blood.V81.2.538.538
language
English
LU publication?
no
id
b8fd0fcf-dd19-400f-a062-0a445572be3d
date added to LUP
2019-12-03 10:34:00
date last changed
2025-01-10 03:49:19
@article{b8fd0fcf-dd19-400f-a062-0a445572be3d,
  abstract     = {{<p>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, there 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.</p>}},
  author       = {{Atlas, E. and Freedman, J. and Blanchette, V. and Kazatchkine, M. D. and Semple, J. W.}},
  issn         = {{0006-4971}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{2}},
  pages        = {{538--542}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{Downregulation of the anti-HLA alloimmune response by variable region- reactive (anti-idiotypic) antibodies in leukemic patients transfused with platelet concentrates}},
  url          = {{http://dx.doi.org/10.1182/blood.V81.2.538.538}},
  doi          = {{10.1182/blood.V81.2.538.538}},
  volume       = {{81}},
  year         = {{1993}},
}