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Antibody to Granulocyte-Macrophage Colony-Stimulating Factor Is a
Dominant Anti-Cytokine Activity in Human IgG Preparations
Morten Svenson,
Morten Bagge Hansen,
Christian Ross,
Marcus Diamant,
Klaus Rieneck,
Henrik Nielsen, and
Klaus Bendtzen
From Lab Med Immunol, and Lab Clin IFN research, Institute for
Inflammation Research, and Dept Clin Immunol, Rigshospitalet University
Hospital, Copenhagen, Denmark.
Pharmaceutical preparations of normal human immunoglobulin (IgG) are
known to contain high-avidity and neutralizing antibodies (Ab) to the
cytokines interleukin (IL)-1 , IL-6, and interferon (IFN). To test
for other cytokine Ab, 23 batches of IgG were tested for saturable
binding to eight 125I-labeled recombinant
cytokines. All batches bound granulocyte-macrophage colony-stimulating
factor (GM-CSF) with high avidity (Kav  10 pmol/L) and capacities
of up to 5 µmol GM-CSF/mol IgG. Only 1 of 15 batches bound IL-5, also
with high avidity, whereas 13 of 15 batches bound to IL-10 but with
lower capacities and avidities. None of the IgG preparations bound IL-1
receptor antagonist (IL-1ra), IL-2, IL-3, IL-4, or G-CSF. Cross-binding
and absorption analyses revealed identical or slightly stronger binding
of recombinant GM-CSF, IL-5, and IL-10 than their native counterparts.
GM-CSF-IgG complexes did not bind to cellular GM-CSF receptors, but
Fc-dependent binding occurred to blood polymorphonuclear cells.
Increased binding of GM-CSF to patient sera correlated positively with
the binding capacities of infused IgG preparations. Patient and normal
sera did not interfere with the binding of Ab to GM-CSF. From these and
previous experiments, we conclude that pools of normal human IgG
contain variable amounts of specific and high-avidity Ab to some
cytokines, and that Ab to GM-CSF constitute a dominant anti-cytokine activity in these preparations. These Ab are available for reaction in vivo following IgG therapy.
Blood, Vol. 91 No. 6 (March 15), 1998:
pp. 2054-2061
© 1998 by The American Society of Hematology.
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