Comparable modulation of human monocyte functions by commercial factor VIII
concentrates of varying purity
JW Mannhalter, R Ahmad, H Leibl, J Gottlicher, HM Wolf and MM Eibl
Institute of Immunology, University of Vienna, Austria.
Our previous observation on immune modulation induced by a given factor
VIII (F VIII) concentrate preparation was extended by showing that the
immune-modulating capacity is a more general feature of F VIII products and
is independent of product purity. Interaction of human monocytes with
therapeutic concentrations of various F VIII concentrates (0.2 to 2 IU F
VIII/mL, six different F VIII concentrates from four manufacturers) led to
a significant reduction in the expression of IgG Fc receptors in the
membrane of these cells (F VIII concentrate-induced downmodulation of the
receptor). This Fc receptor downmodulation was achieved by a short (1-hour)
incubation of human monocytes with F VIII concentrates 16 hours prior to
the Fc receptor assay and did not correlate with the respective product's
IgG content. Although the IgG concentrations of the different products
varied greatly (from 1.0 to 177.3 mg/1,000 IU F VIII), all products behaved
comparably with respect to Fc receptor downmodulation (F VIII-treated
monocytes: 34% +/- 7% to 44% +/- 4% rosette-forming cells; controls in the
absence of F VIII: 83% +/- 5%). Furthermore, we also were able to
demonstrate that heat treatment of F VIII, now used by virtually every
manufacturer to eliminate contaminating viruses, had no effect on the
respective products' Fc receptor-modulating capacity. The immune-modulating
component was characterized as being a high-molecular-range compound
containing IgG, IgM, F VIII, and blood group substances (most likely a
combination of immune complexes and immunoglobulin aggregates). This
compound is present in comparable amounts in both high-purity and
intermediate-purity products and apparently copurifies with F VIII during
the manufacturing process.
Volume 71,
Issue 6,
pp. 1662-1668,
06/01/1988
Copyright © 1988 by The American Society of Hematology