Inhibition of autoantibody binding to platelet glycoprotein IIb/IIIa by
anti-idiotypic antibodies in intravenous gammaglobulin
P Berchtold, GL Dale, P Tani and R McMillan
Department of Molecular and Experimental Medicine, Research Institute of
Scripps Clinic, La Jolla, CA.
Intravenous immunoglobulin (IVIgG) causes an acute rise in the platelet
count in the majority of patients with chronic immune thrombocytopenic
purpura (ITP) but the mechanism(s) of action is still unknown. We evaluated
the ability of three different IVIgG preparations to inhibit the in vitro
binding of autoantibody to platelet glycoprotein (GP) IIb/IIIa. ITP plasma,
known to contain anti-GPIIb/IIIa antibodies, was incubated overnight with
either IVIgG or bovine serum albumin (BSA) followed by measurement of the
autoantibody titer. Binding of autoantibody from eight ITP patients was
inhibited by IVIgG in proportion to the IVIgG concentration. Using 3.2%
IVIgG, compatible with therapeutic concentrations expected in vivo, mean
inhibition of autoantibody binding ranged from 20.2% to 41.3%. No
inhibition by IVIgG of alloantibody binding to the same or different
molecules was detected (five patients with anti-GPIIb/IIIa and two with
anti-HLA alloantibodies). F(ab')2 fragments of IVIgG also inhibited the
binding of both plasma autoantibodies and purified anti-GPIIb/IIIA
autoantibodies prepared by elution from antigen affinity columns. A portion
of the anti-idiotypic antibodies could be adsorbed from IVIgG using
insolubilized, purified anti-GPIIb/IIIa autoantibody. These results show
that IVIgG preparations from normal donors contain anti- idiotypic
antibodies directed against idiotypes located on GPIIb/IIIa autoantibodies
but do not have anti-idiotypes to platelet alloantibodies against the same
or different molecules. The importance of these anti-idiotypic antibodies
in the therapeutic response to IVIgG remains to be established.
Volume 74,
Issue 7,
pp. 2414-2417,
11/15/1989
Copyright © 1989 by The American Society of Hematology
