Heterogeneity of factor VIII antibodies: further immunochemical and
biologic studies
MB Hultin, FS London, SS Shapiro and WJ Yount
Previous studies using immunoneutralization techniques have shown that many
factor VIII inhibitors are IgG antibodies of a single light chain type. We
have investigated this apparent homogeneity by immunoneutralization assay
and liquid isoelectric focusing of inhibitor fractions from five
hemophiliacs and two nonhemophiliacs. By immunoneutralization assay,
inhibitors from four hemophiliacs and one nonhemophiliac were exclusively k
light chain type: the fifth hemophilic inhibitor was predominantly k1 and
the second nonhemophilic inhibitor was a mixture of k and gamma. However,
heavy chain subtyping of the six predominantly or exclusively k inhibitors
showed all to be mixtures of IgG4 and IgG1. By isoelectric focusing, two
inhibitors showed multiple peaks of activity between pH 5 and 9. The
remaining five showed predominant peaks of activity, which were solely
IgGk1 between pH 5.8 and 7, with smaller peaks between pH 7 and 9. The most
acidic major peak, focusing at pH 6, was IgG4 in the three cases tested.
Two of these acidic peaks neutralized factor VIII more efficiently than
other peaks in the same focusing profiles, suggesting greater affinity for
factor VIII. These studies demonstrate that factor VIII inhibitors are
composed of heterogenous subpopulations of immunoglobulins which can be
separated by isoelectric focusing.
Volume 49,
Issue 5,
pp. 807-817,
05/01/1977
Copyright © 1977 by The American Society of Hematology
