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Blood, 1 August 2002, Vol. 100, No. 3, pp. 1055-1059
TRANSFUSION MEDICINE
 -Globulins prepared from sera of multiparous women bind
anti-HLA antibodies and inhibit an established in vivo human
alloimmune response
John W. Semple,
Michael Kim,
Alan H. Lazarus, and
John Freedman
From the Department of Laboratory Medicine and
Pathobiology, St Michael's Hospital, Departments of Pharmacology,
Medicine and Laboratory Medicine, and Pathobiology, University of
Toronto, Canadian Blood Services, and the Toronto Platelet
Immunobiology Group, Toronto, Ontario, Canada.
It has previously been shown that sera from multiparous women have
increased levels of anti-idiotypic antibodies specific for anti-HLA
molecules.  -Globulins prepared from these sera may be superior to
commercial preparations of intravenous -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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