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γ-globulins prepared from sera of multiparous women bind anti-HLA antibodies and inhibit an established in vivo human alloimmune response

Semple, John W. LU ; Kim, Michael ; Lazarus, Alan H. and Freedman, John (2002) In Blood 100(3). p.1055-1059
Abstract

It has previously been shown that sera from multiparous women have increased levels of anti-idiotypic antibodies specific for anti-HLA molecules. γ-Globulins prepared from these sera may be superior to commercial preparations of intravenous γ-globulin (IVIg) for inhibiting HLA alloimmunization. To test this, F(ab′)2 fragments prepared from either commercial IVIg or from the sera of men or multiparous women were coupled to CNBr-Sepharose and tested for their ability to bind F(ab′)2 fragments derived from polyspecific anti-HLA sera. As determined by flow cytometry, compared with columns coated with F(ab′)2 derived from commercial IVIg or sera from men, columns coated with F(ab′)2 prepared from... (More)

It has previously been shown that sera from multiparous women have increased levels of anti-idiotypic antibodies specific for anti-HLA molecules. γ-Globulins prepared from these sera may be superior to commercial preparations of intravenous γ-globulin (IVIg) for inhibiting HLA alloimmunization. To test this, F(ab′)2 fragments prepared from either commercial IVIg or from the sera of men or multiparous women were coupled to CNBr-Sepharose and tested for their ability to bind F(ab′)2 fragments derived from polyspecific anti-HLA sera. As determined by flow cytometry, compared with columns coated with F(ab′)2 derived from commercial IVIg or sera from men, columns coated with F(ab′)2 prepared from the sera of multiparous women bound significantly more anti-HLA. In addition, intact IgG molecules prepared from the sera of multiparous women significantly neutralized the reactivity of the anti-HLA F(ab′)2 fragments. To determine whether the intact IgG molecules or their corresponding F(ab′)2 fragments could affect in vivo alloimmunity, they were tested for their ability to inhibit an established IgG human alloimmune response in humanized severe combined immunodeficient (SCID) mice. Compared with commercial IVIg, when intact IgG or F(ab′)2 fragments derived from multiparous women were administered to SCID mice making human anti-HLA antibodies, a significant reduction in anti-HLA reactivity was observed. The findings suggest that IgG molecules prepared from the sera of multiparous women have increased anti-idiotypic reactivity against anti-HLA antibodies, which can significantly inhibit an established human IgG alloimmune response in an Fc-independent manner.

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author
; ; and
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
100
issue
3
pages
1055 - 1059
publisher
American Society of Hematology
external identifiers
  • pmid:12130522
  • scopus:0036682482
ISSN
0006-4971
DOI
10.1182/blood.V100.3.1055
language
English
LU publication?
no
id
563dccf5-9112-492b-9012-7f2e3a40ac90
date added to LUP
2019-12-03 10:24:36
date last changed
2024-03-20 01:34:07
@article{563dccf5-9112-492b-9012-7f2e3a40ac90,
  abstract     = {{<p>It has previously been shown that sera from multiparous women have increased levels of anti-idiotypic antibodies specific for anti-HLA molecules. γ-Globulins prepared from these sera may be superior to commercial preparations of intravenous γ-globulin (IVIg) for inhibiting HLA alloimmunization. To test this, F(ab′)<sub>2</sub> fragments prepared from either commercial IVIg or from the sera of men or multiparous women were coupled to CNBr-Sepharose and tested for their ability to bind F(ab′)<sub>2</sub> fragments derived from polyspecific anti-HLA sera. As determined by flow cytometry, compared with columns coated with F(ab′)<sub>2</sub> derived from commercial IVIg or sera from men, columns coated with F(ab′)<sub>2</sub> prepared from the sera of multiparous women bound significantly more anti-HLA. In addition, intact IgG molecules prepared from the sera of multiparous women significantly neutralized the reactivity of the anti-HLA F(ab′)<sub>2</sub> fragments. To determine whether the intact IgG molecules or their corresponding F(ab′)<sub>2</sub> fragments could affect in vivo alloimmunity, they were tested for their ability to inhibit an established IgG human alloimmune response in humanized severe combined immunodeficient (SCID) mice. Compared with commercial IVIg, when intact IgG or F(ab′)<sub>2</sub> fragments derived from multiparous women were administered to SCID mice making human anti-HLA antibodies, a significant reduction in anti-HLA reactivity was observed. The findings suggest that IgG molecules prepared from the sera of multiparous women have increased anti-idiotypic reactivity against anti-HLA antibodies, which can significantly inhibit an established human IgG alloimmune response in an Fc-independent manner.</p>}},
  author       = {{Semple, John W. and Kim, Michael and Lazarus, Alan H. and Freedman, John}},
  issn         = {{0006-4971}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{3}},
  pages        = {{1055--1059}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{γ-globulins prepared from sera of multiparous women bind anti-HLA antibodies and inhibit an established in vivo human alloimmune response}},
  url          = {{http://dx.doi.org/10.1182/blood.V100.3.1055}},
  doi          = {{10.1182/blood.V100.3.1055}},
  volume       = {{100}},
  year         = {{2002}},
}